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Trial record 18 of 536 for:    ESCITALOPRAM AND Disorders

Study to Evaluate the Efficacy, Safety and Tolerability of Bupropion Hydrochloride Extended-release Tablet, and Escitalopram Oxalate Capsule in Subjects With Major Depressive Disorder

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ClinicalTrials.gov Identifier: NCT02191397
Recruitment Status : Completed
First Posted : July 16, 2014
Results First Posted : February 18, 2019
Last Update Posted : February 18, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Depressive Disorder, Major
Interventions Drug: Bupropion
Drug: Bupropion Matching Placebo
Drug: Escitalopram
Drug: Escitalopram Matching Placebo
Enrollment 534
Recruitment Details This was a multi-center, randomized, double-blind, parallel active-controlled study to evaluate the efficacy, safety and tolerability of bupropion hydrochloride extended-release (XL) and escitalopram oxalate in participants with major depressive disorder. This study was conducted in China from 10-February-2015 to 25-October-2016.
Pre-assignment Details The study had screening phase (up to 14 days), 8-week double blind treatment phase and taper phase (up to 1 week). A total of 655 participants were screened and 538 were randomized into the study. 4 participants were randomized but discontinued prior to receiving any study treatment. Hence, the Safety Population was comprised of 534 participants.
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation. In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Period Title: Overall Study
Started 266 268
Completed 183 198
Not Completed 83 70
Reason Not Completed
Adverse Event             28             17
Lack of Efficacy             10             5
Protocol Violation             0             3
Met protocol-defined stopping criteria             5             4
Lost to Follow-up             10             11
Physician Decision             8             3
Withdrawal by Subject             22             27
Arm/Group Title Bupropion XL Escitalopram Total
Hide Arm/Group Description In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation. In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation. Total of all reporting groups
Overall Number of Baseline Participants 266 268 534
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 266 participants 268 participants 534 participants
36.9  (11.92) 37.6  (12.09) 37.3  (12.00)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 266 participants 268 participants 534 participants
Female
168
  63.2%
172
  64.2%
340
  63.7%
Male
98
  36.8%
96
  35.8%
194
  36.3%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Asian - East Asian Heritage Number Analyzed 266 participants 268 participants 534 participants
266
 100.0%
268
 100.0%
534
 100.0%
1.Primary Outcome
Title Mean Change in Hamilton Depression Rating Scale - 17 (HAMD-17) Total Score From Baseline to End of Acute Treatment Phase (Week 8)
Hide Description HAMD-17 is used to assess the severity of depression and symptom improvement. It consisted of 17 questions. The HAMD-17 total score is calculated by summing the individual response scores if there is no missing response. HAMD-17 has a total score in a range of 0 (not present) to 52 (severe). Change from Baseline was calculated by subtracting the Baseline total score (at Day 0, Week 0) from Week 8 observed total score. The Per Protocol (PP) Population is defined as all randomized participants in the Intent-To-Treat (ITT) Population who do not meet criteria of a major protocol deviation, with overall compliance of active drug for acute treatment phase in the range of 75%-125% and complete the first 6 weeks treatment and has HAMD-17 assessment at/after week 6 (that is >=35 days). All participants in the PP population were included in the mixed model repeated measures analysis. Only those participants with data available at the specified time point were analyzed.
Time Frame Baseline (Week 0) and Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
PP Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 176 188
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-14.5  (0.41) -15.4  (0.39)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments A one-sided 97.5% confidence interval for the between-treatment difference (bupropion XL-escitalopram) was compared with the pre-defined non-inferiority margin of 2.2. If the upper limit of the one-sided 97.5% confidence interval was below 2.2, then it indicated that bupropion was not inferior in efficacy to escitalopram.
Statistical Test of Hypothesis P-Value 0.139
Comments Analysis included Baseline HAMD-17 total score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-0.27 to 1.94
Estimation Comments Observed Cases (OC) dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
2.Secondary Outcome
Title Response Rate Based on HAMD-17 Total Score
Hide Description HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 total score is calculated by summing the individual response scores if there is no missing response. HAMD-17 has a total score in a range of 0 (not present) to 52 (severe). Values at Day 0, Week 0 was considered as Baseline value. Response was defined as decrease in HAMD-17 total scores at end of acute treatment phase (Week 8) relative to Baseline by at least 50%. Non-responder Imputation was used in calculation of rates.
Time Frame Up to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
PP Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 184 199
Measure Type: Number
Unit of Measure: Percentage of Participants
69.6 72.9
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.479
Comments P-value was estimated from a Generalized Estimating Equation (GEE) model with Response based on HADM-17 as response variable and treatment, gender as explanatory variables.
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.55 to 1.33
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Remission Rate Based on HAMD-17 Total Score
Hide Description HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 total score is calculated by summing the individual response scores if there is no missing response. HAMD-17 has a total score in a range of 0 (not present) to 52 (severe). Values at Day 0, Week 0 was considered as Baseline value. Remission was defined as HAMD-17 total scores at end of acute treatment phase (Week 8) <=7.
Time Frame Up to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
PP Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 184 199
Measure Type: Number
Unit of Measure: Percentage of Participants
39.7 47.2
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.129
Comments P-value was estimated from a Generalized Estimating Equation (GEE) model with Response based on HADM-17 as response variable and treatment, gender as explanatory variables
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.48 to 1.10
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Sustained Response Rate Based on HAMD-17 Total Score
Hide Description HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 total score is calculated by summing the individual response scores if there is no missing response. HAMD-17 has a total score in a range of 0 (not present) to 52 (severe). Values at Day 0, Week 0 was considered as Baseline value. Sustained response was defined as response at end of acute treatment phase and an earlier visit and the decrease from Baseline in non-missing HAMD-17 total scores at all visits between these two visits by at least 40%.
Time Frame Up to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
PP Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 184 199
Measure Type: Number
Unit of Measure: Percentage of Participants
51.6 56.3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.354
Comments P-value was estimated from a GEE model with Response based on HADM-17 as response variable and treatment, gender as explanatory variables
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.55 to 1.24
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Sustained Remission Rate Based on HAMD-17 Total Score
Hide Description HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 total score is calculated by summing the individual response scores if there is no missing response. HAMD-17 has a total score in a range of 0 (not present) to 52 (severe). Values at Day 0, Week 0 was considered as Baseline value. Sustained remission was defined as remission at end of acute treatment phase and an earlier visit and non-missing HAMD-17 total scores at all visits between these two visits <=8.
Time Frame Up to Week 8
Hide Outcome Measure Data
Hide Analysis Population Description
PP Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 184 199
Measure Type: Number
Unit of Measure: Percentage of Participants
25.5 28.6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.489
Comments P-value was estimated from a GEE model with Response based on HADM-17 as response variable and treatment, gender as explanatory variables
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.85
Confidence Interval (2-Sided) 95%
0.54 to 1.34
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at Weeks 1, 2, 4, 6 and 8
Hide Description MADRS is a 10-point rating scale. Each item is scored on a scale of 0-6, with a total score range of 0-60. Higher score indicates worst symptoms. This scale is mainly used to assess the efficacy of antidepressant treatment. The ratings were based on the signs and symptoms during the preceding week prior to the visit. Values at Day0, Week 0 was considered as Baseline value. The observed MADRS total score was considered as missing if any item is missing. Change from Baseline in MADRS was obtained by subtracting the Baseline value from the specific post-Baseline value. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.
Time Frame Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8
Hide Outcome Measure Data
Hide Analysis Population Description
PP Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 184 199
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Week 1, n=184, 199 Number Analyzed 184 participants 199 participants
-3.6  (0.34) -3.8  (0.33)
Week 2, n=182, 199 Number Analyzed 182 participants 199 participants
-7.0  (0.47) -8.3  (0.45)
Week 4, n=184, 198 Number Analyzed 184 participants 198 participants
-11.2  (0.58) -12.4  (0.56)
Week 6, n=183, 196 Number Analyzed 183 participants 196 participants
-15.5  (0.59) -16.3  (0.57)
Week 8, n=176, 188 Number Analyzed 176 participants 188 participants
-18.6  (0.57) -19.5  (0.55)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.627
Comments Analysis included Baseline MADRS total score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.70 to 1.16
Estimation Comments Week 1. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.037
Comments Analysis included Baseline MADRS total score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
0.08 to 2.66
Estimation Comments Week 2. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.143
Comments Analysis included Baseline MADRS total score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-0.40 to 2.78
Estimation Comments Week 4. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.330
Comments Analysis included Baseline MADRS total score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-0.81 to 2.40
Estimation Comments Week 6. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.278
Comments Analysis included Baseline MADRS total score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.9
Confidence Interval (2-Sided) 95%
-0.69 to 2.40
Estimation Comments Week 8. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
7.Secondary Outcome
Title Change From Baseline in HAMD-17 Depressed Mood Subscale Score (Score of Item 1) at Weeks 1, 2, 4, 6 and 8
Hide Description HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 Depressed Mood Subscale is a factor score of item-1 (Depressed Mood) of HAMD-17 scale. This subscale has a score in a range of 0 (absence of depressed mood feelings) to 4 (when participants report virtually only these feeling states in his/her spontaneous verbal and non-verbal communicationtotal score). Values at Day 0, Week 0 was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline response from the specific post-Baseline response. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.
Time Frame Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8
Hide Outcome Measure Data
Hide Analysis Population Description
PP Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 184 199
Least Squares Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Week 1, n=184, 199 Number Analyzed 184 participants 199 participants
-0.4  (0.04) -0.4  (0.04)
Week 2, n=182, 199 Number Analyzed 182 participants 199 participants
-0.7  (0.06) -0.8  (0.05)
Week 4, n=184, 198 Number Analyzed 184 participants 198 participants
-1.1  (0.06) -1.3  (0.06)
Week 6, n=183, 197 Number Analyzed 183 participants 197 participants
-1.5  (0.06) -1.6  (0.06)
Week 8, n=176, 188 Number Analyzed 176 participants 188 participants
-1.9  (0.06) -1.9  (0.06)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.579
Comments Analysis included Baseline HAMD-17 depressed mood subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.09 to 0.16
Estimation Comments Comparison for Week 1. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.163
Comments Analysis included Baseline HAMD-17 depressed mood subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.04 to 0.26
Estimation Comments Comparison for Week 2. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.050
Comments Analysis included Baseline HAMD-17 depressed mood subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
0.00 to 0.34
Estimation Comments Comparison for Week 4. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.337
Comments Analysis included Baseline HAMD-17 depressed mood subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.09 to 0.26
Estimation Comments Comparison for Week 6. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.714
Comments Analysis included Baseline HAMD-17 depressed mood subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.14 to 0.20
Estimation Comments Comparison for Week 8. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
8.Secondary Outcome
Title Change From Baseline in HAMD-17 Anxiety/Somatization Subscale Score (Sum of Scores of Items 10, 11, 12, 13, 15 and 17) at Weeks 1, 2, 4, 6 and 8
Hide Description HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 Anxiety/Somatization subscale score was derived as sum of scores of items 10, 11, 12, 13, 15 and 17 from HAMD-17. This subscale has a score in a range of 0 (absence of condition) to 18 (most severe condition). Values at Day 0, Week 0 was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline response from the specific post-Baseline response. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.
Time Frame Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8
Hide Outcome Measure Data
Hide Analysis Population Description
PP Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 184 199
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Week 1, n=184, 199 Number Analyzed 184 participants 199 participants
-1.3  (0.12) -1.1  (0.12)
Week 2, n=182, 199 Number Analyzed 182 participants 199 participants
-2.0  (0.15) -2.4  (0.14)
Week 4, n=184, 198 Number Analyzed 184 participants 198 participants
-3.0  (0.19) -3.4  (0.18)
Week 6, n=183, 197 Number Analyzed 183 participants 197 participants
-4.0  (0.17) -4.4  (0.17)
Week 8, n=176, 188 Number Analyzed 176 participants 188 participants
-4.8  (0.16) -5.1  (0.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.358
Comments Analysis included Baseline HAMD-17 anxiety/somatization subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.50 to 0.18
Estimation Comments Comparison for Week 1. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.081
Comments Analysis included Baseline HAMD-17 anxiety/somatization subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.04 to 0.75
Estimation Comments Comparison for Week 2. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.062
Comments Analysis included Baseline HAMD-17 anxiety/somatization subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.5
Confidence Interval (2-Sided) 95%
-0.02 to 0.99
Estimation Comments Comparison for Week 4. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.118
Comments Analysis included Baseline HAMD-17 anxiety/somatization subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.10 to 0.85
Estimation Comments Comparison for Week 6. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.252
Comments Analysis included Baseline HAMD-17 anxiety/somatization subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-0.19 to 0.71
Estimation Comments Comparison for Week 8. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
9.Secondary Outcome
Title Change From Baseline in HAMD-17 Retardation Subscale Score (Sum of Scores of Items 1, 7, 8 and 14) at Weeks 1, 2, 4, 6 and 8
Hide Description HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 Retardation subscale score was derived as sum of scores of items 1, 7, 8 and 14 from HAMD-17. This subscale has a score in a range of 0 (absence of condition) to 14 (most severe condition). Values at Day 0, Week 0 was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline response from the specific post-Baseline response. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.
Time Frame Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8
Hide Outcome Measure Data
Hide Analysis Population Description
PP Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 184 199
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Week 1, n=184, 199 Number Analyzed 184 participants 199 participants
-1.0  (0.10) -1.0  (0.10)
Week 2, n=182, 199 Number Analyzed 182 participants 199 participants
-1.8  (0.13) -2.0  (0.13)
Week 4, n=184, 198 Number Analyzed 184 participants 198 participants
-2.9  (0.15) -3.1  (0.15)
Week 6, n=183, 197 Number Analyzed 183 participants 197 participants
-3.9  (0.16) -3.9  (0.16)
Week 8, n=176, 188 Number Analyzed 176 participants 188 participants
-4.7  (0.17) -4.9  (0.16)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.573
Comments Analysis included Baseline HAMD-17 Retardation subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.20 to 0.35
Estimation Comments Comparison for Week 1. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.209
Comments Analysis included Baseline HAMD-17 Retardation subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.13 to 0.58
Estimation Comments Comparison for Week 2. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.427
Comments Analysis included Baseline HAMD-17 Retardation subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.25 to 0.58
Estimation Comments Comparison for Week 4. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.851
Comments Analysis included Baseline HAMD-17 Retardation subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.40 to 0.48
Estimation Comments Comparison for Week 6. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.370
Comments Analysis included Baseline HAMD-17 Retardation subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.25 to 0.66
Estimation Comments Comparison for Week 8. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
10.Secondary Outcome
Title Change From Baseline in HAMD-17 Sleep Disorder Subscale Score (Sum of Scores of Items 4, 5 and 6) at Weeks 1, 2, 4, 6 and 8
Hide Description HAMD-17 is an extensively used tool to assess the severity of depression and symptom improvement during the treatment. The HAMD-17 adopted for this study consisted of 17 questions with multiple choice responses, each of which is numerically scored. The HAMD-17 Sleep Disorder subscale score was derived as sum of scores of items 4, 5 and 6 from HAMD-17. This subscale has a score in a range of 0 (absence of condition) to 6 (most severe condition). Values at Day 0, Week 0 was considered as Baseline value. Change from Baseline was calculated by subtracting the Baseline response from the specific post-Baseline response. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.
Time Frame Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8
Hide Outcome Measure Data
Hide Analysis Population Description
PP Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 184 199
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Week 1, n=184, 199 Number Analyzed 184 participants 199 participants
-0.6  (0.10) -0.7  (0.09)
Week 2, n=182, 199 Number Analyzed 182 participants 199 participants
-0.8  (0.11) -1.2  (0.10)
Week 4, n=184, 198 Number Analyzed 184 participants 198 participants
-1.4  (0.11) -1.6  (0.11)
Week 6, n=183, 197 Number Analyzed 183 participants 197 participants
-1.8  (0.11) -2.0  (0.11)
Week 8, n=176, 188 Number Analyzed 176 participants 188 participants
-2.3  (0.11) -2.4  (0.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.438
Comments Analysis included Baseline HAMD-17 Sleep Disorder subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.16 to 0.37
Estimation Comments Comparison for Week 1. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments Analysis included Baseline HAMD-17 Sleep Disorder subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
0.07 to 0.66
Estimation Comments Comparison for Week 2. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.207
Comments Analysis included Baseline HAMD-17 Sleep Disorder subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.11 to 0.50
Estimation Comments Comparison for Week 4. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.137
Comments Analysis included Baseline HAMD-17 Sleep Disorder subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.07 to 0.54
Estimation Comments Comparison for Week 6. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.299
Comments Analysis included Baseline HAMD-17 Sleep Disorder subscale score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.14 to 0.46
Estimation Comments Comparison for Week 8. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
11.Secondary Outcome
Title Change From Baseline in Clinical Global Impression-Severity of Illness Scale (CGI-S) Score at Weeks 1, 2, 4, 6 and 8
Hide Description CGI-S records the severity of illness at specific time points, with a range of responses from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Participants with zero values (0) representing "Not assessed" were excluded from analysis. Values at Day 0, Week 0 was considered as Baseline value. Change from Baseline was obtained by subtracting the Baseline value from the specific post-Baseline value. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.
Time Frame Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8
Hide Outcome Measure Data
Hide Analysis Population Description
PP Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 184 199
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
Week 1, n=184, 199 Number Analyzed 184 participants 199 participants
-0.3  (0.04) -0.4  (0.04)
Week 2, n=182, 199 Number Analyzed 182 participants 199 participants
-0.7  (0.05) -0.8  (0.05)
Week 4, n=184, 198 Number Analyzed 184 participants 198 participants
-1.1  (0.07) -1.3  (0.06)
Week 6, n=183, 197 Number Analyzed 183 participants 197 participants
-1.6  (0.07) -1.7  (0.07)
Week 8, n=176, 188 Number Analyzed 176 participants 188 participants
-2.1  (0.07) -2.2  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.804
Comments Analysis included Baseline CGI-S score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.10 to 0.13
Estimation Comments Comparison for Week 1. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.079
Comments Analysis included Baseline CGI-S score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.02 to 0.28
Estimation Comments Comparison for Week 2. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.036
Comments Analysis included Baseline CGI-S score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
0.01 to 0.38
Estimation Comments Comparison for Week 4. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.248
Comments Analysis included Baseline CGI-S score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-0.08 to 0.31
Estimation Comments Comparison for Week 6. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.110
Comments Analysis included Baseline CGI-S score as covariate, treatment, gender, visit and treatment-visit interaction as fixed effects. Unstructured covariance matrix was used.
Method Mixed model repeated measures analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-0.04 to 0.35
Estimation Comments Comparison for Week 8. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
12.Secondary Outcome
Title Percentage of Participants With a Clinical Global Impression Global Improvement (CGI-I) Score of 1 ("Very Much Improved") or 2 ("Much Improved") at Weeks 1, 2, 4, 6 and 8
Hide Description For CGI-I rating, the raters indicated their assessment of the participant's total improvement or worsening compared to the participant’s condition at the Baseline visit, whether or not the improvement or worsening was thought to be treatment related. Scores ranges from 0 to 7 where 0 represents "Not assessed", and the remaining values 1-7 represent "Very much improved" (1) to "Very much worse" (7). Participants with score 0 were excluded from analysis. All participants in the PP population were analyzed and n=X in the category titles represented the number of participants with data available at the specified time points.
Time Frame Baseline (Week 0) and Weeks 1, 2, 4, 6 and 8
Hide Outcome Measure Data
Hide Analysis Population Description
PP Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 184 199
Measure Type: Number
Unit of Measure: Percentage of Participants
Week 1, n=184, 199 Number Analyzed 184 participants 199 participants
6 7.5
Week 2, n=182, 199 Number Analyzed 182 participants 199 participants
21.4 22.1
Week 4, n=184, 198 Number Analyzed 184 participants 198 participants
38.6 52.5
Week 6, n=183, 197 Number Analyzed 183 participants 197 participants
67.8 71.6
Week 8, n=176, 188 Number Analyzed 176 participants 188 participants
80.7 83.5
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.545
Comments P-value was estimated from a GEE model repeated measures with CGI-I score of 1 or 2 as response variable and treatment, gender as explanatory variables
Method GEE model repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio, log
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.35 to 1.75
Estimation Comments Comparison for Week 1. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.822
Comments P-value was estimated from a GEE model repeated measures with CGI-I score of 1 or 2 as response variable and treatment, gender as explanatory variables
Method GEE model repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.58 to 1.54
Estimation Comments Comparison for Week 2. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments P-value was estimated from a GEE model repeated measures with CGI-I score of 1 or 2 as response variable and treatment, gender as explanatory variables
Method GEE model repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
0.38 to 0.86
Estimation Comments Comparison for Week 4. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.417
Comments P-value was estimated from a GEE model repeated measures with CGI-I score of 1 or 2 as response variable and treatment, gender as explanatory variables
Method GEE model repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.54 to 1.29
Estimation Comments Comparison for Week 6. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Bupropion XL, Escitalopram
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.485
Comments P-value was estimated from a GEE model repeated measures with CGI-I score of 1 or 2 as response variable and treatment, gender as explanatory variables
Method GEE model repeated measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.49 to 1.40
Estimation Comments Comparison for Week 8. OC dataset was used, where available data at a given time point was used with no missing values filled in with estimates.
13.Secondary Outcome
Title Number of Participants With Any Non-serious Adverse Event (AE) and Any Serious AE (SAE)
Hide Description An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Participants who received any of the study treatment and had any non-serious AE or SAE were considered for analysis. Safety Population comprised of all participants who took at least one dose of the study medication.
Time Frame Up to Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 266 268
Measure Type: Count of Participants
Unit of Measure: Participants
Any non-serious AE
151
  56.8%
150
  56.0%
Any SAE
10
   3.8%
11
   4.1%
14.Secondary Outcome
Title Change From Baseline in Hemoglobin, Total Protein, Albumin and Mean Corpuscle Hemoglobin Concentration (MCHC) at the Indicated Time Points
Hide Description Blood samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Baseline was considered as the value obtained at Screening. Change from Baseline was calculated by subtracting the Baseline value from the specific post-Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame Up to Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 266 268
Mean (Standard Deviation)
Unit of Measure: Gram per Liter (G/L)
Hemoglobin, Week 8, n=176, 183 Number Analyzed 176 participants 183 participants
-0.22  (7.621) -1.16  (7.874)
Hemoglobin, Taper, n=13, 16 Number Analyzed 13 participants 16 participants
-1.54  (5.868) 1.38  (8.057)
Hemoglobin, Follow-up, n=10, 8 Number Analyzed 10 participants 8 participants
-3.10  (12.449) 0.38  (6.163)
Total protein, Week 8, n=174, 183 Number Analyzed 174 participants 183 participants
-0.640  (5.2784) -0.891  (4.0339)
Total protein, Taper, n=12, 15 Number Analyzed 12 participants 15 participants
1.197  (6.9347) 2.000  (8.7513)
Total protein, Follow-up, n=8, 12 Number Analyzed 8 participants 12 participants
-4.650  (5.5131) -1.227  (4.8619)
Albumin, Week 8, n=175, 183 Number Analyzed 175 participants 183 participants
-0.254  (3.0207) -0.678  (2.8483)
Albumin, Taper, n=12, 15 Number Analyzed 12 participants 15 participants
-0.086  (3.9688) -0.027  (4.2372)
Albumin, Follow-up, n=8, 12 Number Analyzed 8 participants 12 participants
-1.925  (2.0084) -1.577  (3.6313)
MCHC, Week 8, n=176, 183 Number Analyzed 176 participants 183 participants
-0.09  (8.933) 0.76  (9.821)
MCHC, Taper, n=13, 16 Number Analyzed 13 participants 16 participants
0.54  (8.828) 2.25  (9.030)
MCHC, Follow-up, n=10, 8 Number Analyzed 10 participants 8 participants
-2.10  (9.398) -2.88  (5.055)
15.Secondary Outcome
Title Change From Baseline in Hematocrit at the Indicated Time Points
Hide Description Blood samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Baseline was considered as the value obtained at Screening. Change from Baseline was calculated by subtracting the Baseline value from the specific post-Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame Up to Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 266 268
Mean (Standard Deviation)
Unit of Measure: Proportion of red blood cells in blood
Hematocrit, Week 8, n=176, 183 Number Analyzed 176 participants 183 participants
0.0016  (0.06088) -0.0044  (0.02587)
Hematocrit, Taper, n=13, 16 Number Analyzed 13 participants 16 participants
-0.0051  (0.02105) 0.0017  (0.02601)
Hematocrit, Follow-up, n=10, 8 Number Analyzed 10 participants 8 participants
-0.0076  (0.04403) 0.0051  (0.01509)
16.Secondary Outcome
Title Change From Baseline in White Blood Cell (WBC) Count, Total Neutrophil, Lymphocyte, Basophil, Eosinophil, Monocyte and Platelet Count at the Indicated Time Points
Hide Description Blood samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Baseline was considered as the value obtained at Screening. Change from Baseline was calculated by subtracting the Baseline value from the specific post-Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame Up to Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 266 268
Mean (Standard Deviation)
Unit of Measure: Giga cells per liter (GI/L)
WBC count, Week 8, n=176, 183 Number Analyzed 176 participants 183 participants
-0.032  (1.6278) -0.073  (1.6282)
WBC count, Taper, n=13, 16 Number Analyzed 13 participants 16 participants
0.065  (1.5513) -0.715  (1.8547)
WBC count, Follow-up, n=10, 8 Number Analyzed 10 participants 8 participants
-0.743  (1.4455) 0.427  (0.9032)
Total Neutrophils, Week 8, n=176, 183 Number Analyzed 176 participants 183 participants
0.101  (1.4835) -0.165  (1.5540)
Total Neutrophils, Taper, n=13, 16 Number Analyzed 13 participants 16 participants
0.306  (1.6222) -0.772  (1.5656)
Total Neutrophils, Follow-up, n=10, 8 Number Analyzed 10 participants 8 participants
-0.869  (1.4578) 0.424  (0.7470)
Lymphocytes, Week 8, n=176, 183 Number Analyzed 176 participants 183 participants
-0.154  (0.4833) 0.072  (0.4190)
Lymphocytes, Taper, n=13, 16 Number Analyzed 13 participants 16 participants
-0.242  (0.4843) 0.077  (0.5053)
Lymphocytes, Follow-up, n=10, 8 Number Analyzed 10 participants 8 participants
0.042  (0.3937) 0.022  (0.4388)
Basophil, Week 8, n=176, 182 Number Analyzed 176 participants 182 participants
0.001  (0.0173) 0.002  (0.0218)
Basophil, Taper, n=13, 16 Number Analyzed 13 participants 16 participants
0.001  (0.0091) 0.001  (0.0131)
Basophil, Follow-up, n=10, 8 Number Analyzed 10 participants 8 participants
-0.003  (0.0163) -0.012  (0.0087)
Eosinophil, Week 8, n=176, 182 Number Analyzed 176 participants 182 participants
-0.004  (0.0788) 0.010  (0.0899)
Eosinophil, Taper, n=13, 16 Number Analyzed 13 participants 16 participants
-0.012  (0.0592) 0.006  (0.0488)
Eosinophil, Follow-up, n=10, 8 Number Analyzed 10 participants 8 participants
-0.005  (0.0627) 0.019  (0.0813)
Monocyte, Week 8, n=176, 182 Number Analyzed 176 participants 182 participants
0.021  (0.1180) 0.003  (0.1113)
Monocyte, Taper, n=13, 16 Number Analyzed 13 participants 16 participants
-0.001  (0.1023) -0.031  (0.0917)
Monocyte, Follow-up, n=10, 8 Number Analyzed 10 participants 8 participants
0.058  (0.1292) 0.010  (0.0920)
Platelet count, Week 8, n=176, 183 Number Analyzed 176 participants 183 participants
7.73  (32.725) 0.56  (29.492)
Platelet count, Taper, n=13, 16 Number Analyzed 13 participants 16 participants
17.15  (35.126) 7.19  (22.448)
Platelet count, Follow-up, n=10, 8 Number Analyzed 10 participants 8 participants
28.50  (35.600) 5.38  (24.784)
17.Secondary Outcome
Title Change From Baseline in Total Bilirubin, Direct Bilirubin and Creatinine at the Indicated Time Points
Hide Description Blood samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Baseline was considered as the value obtained at Screening. Change from Baseline was calculated by subtracting the Baseline value from the specific post-Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame Up to Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 266 268
Mean (Standard Deviation)
Unit of Measure: Micromoles per liter (µmol/L)
Total bilirubin, Week 8, n=175, 181 Number Analyzed 175 participants 181 participants
-0.812  (4.7591) -0.071  (4.8022)
Total bilirubin, Taper, n=12, 15 Number Analyzed 12 participants 15 participants
-3.457  (6.5521) 1.198  (3.9442)
Total bilirubin, Follow-up, n=8, 12 Number Analyzed 8 participants 12 participants
0.382  (4.0151) 0.338  (3.4710)
Direct bilirubin, Week 8, n=175, 180 Number Analyzed 175 participants 180 participants
-0.072  (1.3659) -0.006  (1.2310)
Direct bilirubin, Taper, n=11, 15 Number Analyzed 11 participants 15 participants
-1.554  (3.7607) 0.654  (1.7145)
Direct bilirubin, Follow-up, n=8, 12 Number Analyzed 8 participants 12 participants
-0.102  (1.1192) 0.382  (0.9070)
Creatinine, Week 8, n=174, 183 Number Analyzed 174 participants 183 participants
7.507  (10.6852) 0.307  (9.0811)
Creatinine, Taper, n=12, 15 Number Analyzed 12 participants 15 participants
6.675  (6.9134) 0.880  (10.3281)
Creatinine, Follow-up, n=8, 11 Number Analyzed 8 participants 11 participants
4.237  (8.9291) 1.618  (9.6668)
18.Secondary Outcome
Title Change From Baseline in Alanine Aminotransferase (ALT), Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Gamma-glutamyl Transpeptidase (GGT) and Lactose Dehydrogenase (LD) at the Indicated Time Points
Hide Description Blood samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Baseline was considered as the value obtained at Screening. Change from Baseline was calculated by subtracting the Baseline value from the specific post-Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame Up to Week 10
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Safety Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 266 268
Mean (Standard Deviation)
Unit of Measure: International Units per liter (IU/L)
ALT, Week 8, n=176, 183 Number Analyzed 176 participants 183 participants
2.254  (14.7208) 1.315  (10.3019)
ALT, Taper, n=12, 16 Number Analyzed 12 participants 16 participants
7.993  (17.5985) -1.812  (15.1544)
ALT, Follow-up, n=8, 12 Number Analyzed 8 participants 12 participants
-7.337  (21.7809) 5.938  (19.8234)
ALP, Week 8, n=176, 181 Number Analyzed 176 participants 181 participants
1.866  (13.2776) 0.407  (11.7870)
ALP, Taper, n=12, 15 Number Analyzed 12 participants 15 participants
3.674  (11.5803) 3.480  (19.2823)
ALP, Follow-up, n=7, 12 Number Analyzed 7 participants 12 participants
5.643  (9.2858) -3.953  (11.6377)
AST, Week 8, n=176, 183 Number Analyzed 176 participants 183 participants
0.330  (7.6259) 1.099  (6.1029)
AST, Taper, n=12, 16 Number Analyzed 12 participants 16 participants
3.193  (7.4990) 0.381  (6.0938)
AST, Follow-up, n=8, 12 Number Analyzed 8 participants 12 participants
0.925  (23.3485) 2.867  (11.0264)
GGT, Week 8, n=175, 181 Number Analyzed 175 participants 181 participants
0.688  (17.0699) -0.694  (11.1878)
GGT, Taper, n=12, 15 Number Analyzed 12 participants 15 participants
1.403  (6.2977) -3.133  (4.8019)
GGT, Follow-up, n=7, 12 Number Analyzed 7 participants 12 participants
-2.029  (5.9637) 3.916  (25.9888)
LD, Week 8, n=176, 182 Number Analyzed 176 participants 182 participants
1.292  (32.4627) 2.879  (27.3838)
LD, Taper, n=13, 13 Number Analyzed 13 participants 13 participants
14.463  (28.9571) -8.092  (55.0095)
LD, Follow-up, n=8, 10 Number Analyzed 8 participants 10 participants
11.037  (45.3316) -4.150  (33.8871)
19.Secondary Outcome
Title Change From Baseline in Calcium, Chloride, Cholesterol, Glucose, Potassium, Sodium, Triglyceride and Urea at the Indicated Time Points
Hide Description Blood samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Baseline was considered as the value obtained at Screening. Change from Baseline was calculated by subtracting the Baseline value from the specific post-Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame Up to Week 10
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Safety Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 266 268
Mean (Standard Deviation)
Unit of Measure: Millimole per liter (mmol/L)
Calcium, Week 8, n=173, 183 Number Analyzed 173 participants 183 participants
-0.017  (0.1139) -0.020  (0.1225)
Calcium, Taper, n=12, 12 Number Analyzed 12 participants 12 participants
-0.019  (0.1906) 0.012  (0.1091)
Calcium, Follow-up, n=8, 11 Number Analyzed 8 participants 11 participants
-0.060  (0.1032) -0.060  (0.1352)
Chloride, Week 8, n=173, 182 Number Analyzed 173 participants 182 participants
0.259  (2.7943) -0.293  (2.5913)
Chloride, Taper, n=10, 13 Number Analyzed 10 participants 13 participants
-0.498  (3.2001) -0.566  (2.4684)
Chloride, Follow-up, n=8, 8 Number Analyzed 8 participants 8 participants
-0.287  (3.6588) -0.178  (4.6453)
Cholesterol, Week 8, n=175, 181 Number Analyzed 175 participants 181 participants
-0.122  (0.5855) 0.051  (0.5931)
Cholesterol, Taper, n=12, 14 Number Analyzed 12 participants 14 participants
0.022  (0.5891) 0.082  (0.5991)
Cholesterol, Follow-up, n=9, 11 Number Analyzed 9 participants 11 participants
-0.124  (0.5149) -0.122  (0.5899)
Glucose, Week 8, n=173, 181 Number Analyzed 173 participants 181 participants
-0.051  (0.6327) -0.050  (0.5871)
Glucose, Taper, n=12, 16 Number Analyzed 12 participants 16 participants
0.352  (0.3822) 0.106  (0.9661)
Glucose, Follow-up, n=9, 11 Number Analyzed 9 participants 11 participants
-0.194  (0.4089) 0.025  (1.2117)
Potassium, Week 8, n=173, 182 Number Analyzed 173 participants 182 participants
-0.021  (0.3504) 0.009  (0.3552)
Potassium, Taper, n=10, 13 Number Analyzed 10 participants 13 participants
-0.114  (0.4165) 0.046  (0.5095)
Potassium, Follow-up, n=8, 8 Number Analyzed 8 participants 8 participants
-0.110  (0.6221) 0.036  (0.6556)
Sodium, Week 8, n=173, 182 Number Analyzed 173 participants 182 participants
-0.205  (2.4757) -0.178  (2.5481)
Sodium, Taper, n=10, 13 Number Analyzed 10 participants 13 participants
-0.611  (3.0799) 0.978  (1.5853)
Sodium, Follow-up, n=8, 8 Number Analyzed 8 participants 8 participants
-0.175  (3.9085) 0.770  (3.6011)
Triglycerides, Week 8, n=175, 181 Number Analyzed 175 participants 181 participants
0.003  (1.0499) 0.022  (0.5844)
Triglycerides, Taper, n=13, 15 Number Analyzed 13 participants 15 participants
-0.032  (0.4359) 0.574  (2.0355)
Triglycerides, Follow-up, n=9, 11 Number Analyzed 9 participants 11 participants
0.637  (1.4045) 0.181  (0.7767)
Urea, Week 8, n=174, 183 Number Analyzed 174 participants 183 participants
-0.068  (1.3282) 0.015  (1.1723)
Urea, Taper, n=12, 16 Number Analyzed 12 participants 16 participants
0.517  (0.9249) -0.269  (1.0223)
Urea, Follow-up, n=8, 11 Number Analyzed 8 participants 11 participants
0.687  (0.6998) -0.419  (1.0801)
20.Secondary Outcome
Title Change From Baseline in Mean Corpuscle Hemoglobin (MCH) at the Indicated Time Points
Hide Description Blood samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Baseline was considered as the value obtained at Screening. Change from Baseline was calculated by subtracting the Baseline value from the specific post-Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame Up to Week 10
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Safety Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 266 268
Mean (Standard Deviation)
Unit of Measure: Picograms
MCH, Week 8, n=176, 183 Number Analyzed 176 participants 183 participants
-0.032  (0.7431) 0.049  (0.7052)
MCH, Taper, n=13, 16 Number Analyzed 13 participants 16 participants
0.269  (0.7941) 0.262  (0.7571)
MCH, Follow-up, n=10, 8 Number Analyzed 10 participants 8 participants
-0.050  (1.1909) -0.250  (0.4598)
21.Secondary Outcome
Title Change From Baseline in Mean Corpuscle Volume (MCV) at the Indicated Time Points
Hide Description Blood samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Baseline was considered as the value obtained at Screening. Change from Baseline was calculated by subtracting the Baseline value from the specific post-Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame Up to Week 10
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 266 268
Mean (Standard Deviation)
Unit of Measure: Femtoliter
MCV, Week 8, n=176, 183 Number Analyzed 176 participants 183 participants
4.668  (62.5158) -0.090  (2.4759)
MCV, Taper, n=13, 16 Number Analyzed 13 participants 16 participants
0.508  (2.2291) 0.181  (2.1201)
MCV, Follow-up, n=10, 8 Number Analyzed 10 participants 8 participants
0.320  (3.3565) 0.287  (1.1205)
22.Secondary Outcome
Title Change From Baseline in Red Blood Cell (RBC) Count at the Indicated Time Points
Hide Description Blood samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Baseline was considered as the value obtained at Screening. Change from Baseline was calculated by subtracting the Baseline value from the specific post-Baseline values. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame Up to Week 10
Hide Outcome Measure Data
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Safety Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 266 268
Mean (Standard Deviation)
Unit of Measure: 10^12 cells per liter
RBC Count, Week 8, n=176, 183 Number Analyzed 176 participants 183 participants
-0.009  (0.2711) -0.049  (0.2563)
RBC Count, Taper, n=13, 16 Number Analyzed 13 participants 16 participants
-0.088  (0.1599) -0.007  (0.2560)
RBC Count, Follow-up, n=10, 8 Number Analyzed 10 participants 8 participants
-0.132  (0.4018) 0.036  (0.1859)
23.Secondary Outcome
Title Number of Participants With Urinalysis Data Outside the Normal Range
Hide Description Urine samples were collected at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). Number of participants with urine specific gravity and potential of hydrogen (pH) outside (higher or lower) the normal range are presented. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame Up to Week 10
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Safety Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 266 268
Measure Type: Number
Unit of Measure: Participants
Urine specific gravity, high,Screening, n=265, 255 Number Analyzed 265 participants 255 participants
20 12
Urine specific gravity, low,Screening, n=265, 255 Number Analyzed 265 participants 255 participants
1 1
Urine specific gravity,high, Week 8, n=171, 173 Number Analyzed 171 participants 173 participants
9 7
Urine specific gravity,low, Week 8, n=171, 173 Number Analyzed 171 participants 173 participants
0 1
Urine specific gravity, high, Taper, n=18, 28 Number Analyzed 18 participants 28 participants
0 0
Urine specific gravity, low, Taper, n=18, 28 Number Analyzed 18 participants 28 participants
0 1
Urine specific gravity, high, Follow-up, n=7, 14 Number Analyzed 7 participants 14 participants
0 3
Urine specific gravity, low, Follow-up, n=7, 14 Number Analyzed 7 participants 14 participants
0 0
Urine pH, high, Screening, n=265, 266 Number Analyzed 265 participants 266 participants
7 18
Urine pH, low, Screening, n=265, 266 Number Analyzed 265 participants 266 participants
37 28
Urine pH, high, Week 8, n=172, 178 Number Analyzed 172 participants 178 participants
5 9
Urine pH, low, Week 8, n=172, 178 Number Analyzed 172 participants 178 participants
23 20
Urine pH, high, Taper, n=18, 28 Number Analyzed 18 participants 28 participants
0 1
Urine pH, low, Taper, n=18, 28 Number Analyzed 18 participants 28 participants
2 2
Urine pH, high, Follow-up, n=7, 14 Number Analyzed 7 participants 14 participants
0 0
Urine pH, low, Follow-up, n=7, 14 Number Analyzed 7 participants 14 participants
2 2
24.Secondary Outcome
Title Number of Participants With Vital Sign Parameters Outside the Clinical Concern Range
Hide Description Vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were taken at Screening (within 14 days prior to dosing), randomization visit (Week 0) and at Weeks 1, 2, 4, 6, 8, Taper visit (Week 9) and Follow-up visit (Week 10). SBP <30 or >170 millimeter of mercury (mmHg); DBP <20 or >110 mmHg and heart rate <40 or >120 beats per minute (bpm) were considered as values outside of clinical concern range and were presented as 'High' or 'Low' values. Number of participants with vital signs outside of clinical concern range at any post-Baseline visit are presented. Only those participants with data available at the specified time points were analyzed.
Time Frame Up to Week 10
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Safety Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 260 253
Measure Type: Number
Unit of Measure: Participants
SBP, high, Any visit post-Baseline 1 0
SBP, low,Any visit post-Baseline 0 0
DBP, high, Any visit post-Baseline 0 0
DBP, low, Any visit post-Baseline 0 0
HR, high, Any visit post-Baseline 0 1
HR, low, Any visit post-Baseline 0 0
25.Secondary Outcome
Title Number of Participants With Electrocardiogram (ECG) Data Outside the Clinical Concern Range
Hide Description ECG was recorded at Screening (within 14 days prior to dosing) and at Week 8, Taper visit (Week 9) and Follow-up visit (Week 10). PR interval <110 or >220 millisecond (msec); QRS interval <60 or >120 msec and corrected QT (QTc) interval >450 msec were considered as values outside of clinical concern range and were presented as 'High' or 'Low' values. Number of participants with ECG data outside of clinical concern range at any post-Baseline visit are presented. Only those participants with data available at the specified time points were analyzed.
Time Frame Up to Week 10
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Safety Population
Arm/Group Title Bupropion XL Escitalopram
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In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 224 222
Measure Type: Number
Unit of Measure: Participants
PR interval, high, Any visit post-randomization 0 0
PR interval, low,Any visit post-randomization 5 2
QRS interval, high, Any visit post-randomization 2 3
QRS interval, low, Any visit post-randomization 0 1
QTc interval, high, Any visit post-randomization 1 3
QTc interval, low, Any visit post-randomization 0 0
26.Secondary Outcome
Title Change From Baseline in Changes in Sexual Function Questionnaire (CSFQ)
Hide Description CSFQ is a questionnaire about sexual activity and sexual function (sexual intercourse, masturbation, sexual fantasies and other activity). CSFQ is a gender-specific questionnaire. Both male and female versions consist of 14 items, each with 5 possible answers. CSFQ has a score in a range of 14 to 70. Higher score indicates higher sexual activity and sexual function. Value at Day 0 (Week 0) was considered as Baseline value. Change from Baseline at Week 8 was calculated by subtracting the Baseline score from the specific post-Baseline score. Only those participants with data available at the specified time points were analyzed.
Time Frame Baseline (Day 0) and Week 8
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Safety Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 173 179
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
3.0  (6.47) 0.9  (7.21)
27.Secondary Outcome
Title Number of Participants With Suicidal Ideation or Behavior During Treatment Assessed by Columbia Suicide Severity Rating Scale (C-SSRS)
Hide Description C-SSRS is an assessment tool that evaluates suicidal ideation and behavior. It consists of 10 items, each with two possible answers (yes/no). Suicidal ideation was interpreted if “yes” answer at any time during treatment to any one of the five suicidal ideation questions (item 1-5) on the C-SSRS. Suicidal behavior was interpreted if a “yes” answer at any time during treatment to any one of the five suicidal behavior questions (item 6-10) on the C-SSRS. Suicidal ideation or behavior is interpreted if a “yes” answer at any time during treatment to any one of the ten suicidal ideation and behavior questions (item 1-10) on the C-SSRS. Number of participants with at least one on-treatment C-SSRS assessment were analyzed. Only those participants with data available at the specified time points were analyzed.
Time Frame Baseline and up to Taper visit (Week 9)
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Safety Population
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description:
In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
Overall Number of Participants Analyzed 255 249
Measure Type: Number
Unit of Measure: Participants
Suicidal Ideation or Behavior 50 43
Suicidal Ideation 50 43
Suicidal Behavior 2 1
Self-Injurious Behavior, no suicidal attempt 1 1
Time Frame Adverse events (AEs) were collected from the start of study treatment and until the end safety follow-up visit (up to Week 10). SAEs were recorded from the time the consent form is signed until the follow-up visit (up to Week 10).
Adverse Event Reporting Description SAEs and non-serious AEs were reported for the Safety Population which comprised of all participants who took at least one dose of the study medication.
 
Arm/Group Title Bupropion XL Escitalopram
Hide Arm/Group Description In a double-blind 8-week acute treatment phase, participants received 1 tablet of bupropion XL 150 milligram (mg) per day at dose level 1 (Week 0 to Week 1). At dose level 2 (Week 1 to Week 4), bupropion XL dose was increased to 300 mg per day (2 tablets of bupropion XL 150 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), bupropion XL dose was still maintained at 300 mg per day (2 tablets of bupropion XL 150 mg). To ensure study blind, the participants were dosed with placebo matching escitalopram at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation. In a double-blind 8-week acute treatment phase, participants received 1 capsule of escitalopram 10 mg per day at dose level 1 (Week 0 to Week 1). Escitalopram dose was maintained at 10 mg per day (1 capsule of Escitalopram 10 mg) for further 3 weeks to ensure that participants had achieved the clinical recommended dose. At dose level 3 (Week 4 to Week 8), the escitalopram dose could be increased to 20 mg per day (2 capsule of Escitalopram 10 mg). To ensure study blind, the participants were also dosed with placebo matching bupropion XL at each dose level. After treatment phase, participants entered in taper phase where dose in was down-titrated step by step to reduce the possible withdrawal symptoms. In taper phase, both dose level 2 and dose level 3 were down titrated to dose level 1 for 1 week before discontinuation.
All-Cause Mortality
Bupropion XL Escitalopram
Affected / at Risk (%) Affected / at Risk (%)
Total   1/266 (0.38%)   0/268 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Bupropion XL Escitalopram
Affected / at Risk (%) Affected / at Risk (%)
Total   10/266 (3.76%)   11/268 (4.10%) 
Ear and labyrinth disorders     
Tinnitus  1  1/266 (0.38%)  0/268 (0.00%) 
Infections and infestations     
Upper respiratory tract infection  1  0/266 (0.00%)  1/268 (0.37%) 
Conjunctivitis  1  1/266 (0.38%)  0/268 (0.00%) 
Pneumonia  1  0/266 (0.00%)  1/268 (0.37%) 
Injury, poisoning and procedural complications     
Lacrimal structure injury  1  1/266 (0.38%)  0/268 (0.00%) 
Muscle injury  1  0/266 (0.00%)  1/268 (0.37%) 
Overdose  1  1/266 (0.38%)  0/268 (0.00%) 
Radial nerve injury  1  0/266 (0.00%)  1/268 (0.37%) 
Rib fracture  1  0/266 (0.00%)  1/268 (0.37%) 
Investigations     
Blood pressure increased  1  0/266 (0.00%)  1/268 (0.37%) 
Metabolism and nutrition disorders     
Electrolyte imbalance  1  0/266 (0.00%)  1/268 (0.37%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Brain neoplasm  1  0/266 (0.00%)  1/268 (0.37%) 
Psychiatric disorders     
Depression  1  2/266 (0.75%)  4/268 (1.49%) 
Depression suicidal  1  1/266 (0.38%)  0/268 (0.00%) 
Intentional self-injury  1  0/266 (0.00%)  1/268 (0.37%) 
Major depression  1  0/266 (0.00%)  1/268 (0.37%) 
Somatic symptom disorder  1  1/266 (0.38%)  0/268 (0.00%) 
Suicide attempt  1  1/266 (0.38%)  0/268 (0.00%) 
Skin and subcutaneous tissue disorders     
Urticaria  1  1/266 (0.38%)  0/268 (0.00%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Bupropion XL Escitalopram
Affected / at Risk (%) Affected / at Risk (%)
Total   151/266 (56.77%)   150/268 (55.97%) 
Blood and lymphatic system disorders     
White blood cell disorder  1  1/266 (0.38%)  0/268 (0.00%) 
Cardiac disorders     
Palpitations  1  11/266 (4.14%)  5/268 (1.87%) 
Tachycardia  1  3/266 (1.13%)  0/268 (0.00%) 
Bundle branch block right  1  0/266 (0.00%)  1/268 (0.37%) 
Defect conduction intraventricular  1  1/266 (0.38%)  0/268 (0.00%) 
Sinus bradycardia  1  0/266 (0.00%)  1/268 (0.37%) 
Ear and labyrinth disorders     
Tinnitus  1  4/266 (1.50%)  2/268 (0.75%) 
Ear discomfort  1  1/266 (0.38%)  0/268 (0.00%) 
Motion sickness  1  1/266 (0.38%)  0/268 (0.00%) 
Vertigo  1  1/266 (0.38%)  0/268 (0.00%) 
Eye disorders     
Vision blurred  1  2/266 (0.75%)  1/268 (0.37%) 
Eye pain  1  1/266 (0.38%)  0/268 (0.00%) 
Ocular discomfort  1  1/266 (0.38%)  0/268 (0.00%) 
Photopsia  1  0/266 (0.00%)  1/268 (0.37%) 
Gastrointestinal disorders     
Nausea  1  28/266 (10.53%)  50/268 (18.66%) 
Dry mouth  1  16/266 (6.02%)  15/268 (5.60%) 
Constipation  1  14/266 (5.26%)  9/268 (3.36%) 
Abdominal discomfort  1  9/266 (3.38%)  9/268 (3.36%) 
Diarrhoea  1  4/266 (1.50%)  6/268 (2.24%) 
Vomiting  1  7/266 (2.63%)  3/268 (1.12%) 
Abdominal pain upper  1  5/266 (1.88%)  1/268 (0.37%) 
Abdominal distension  1  3/266 (1.13%)  2/268 (0.75%) 
Abdominal pain  1  4/266 (1.50%)  1/268 (0.37%) 
Epigastric discomfort  1  1/266 (0.38%)  1/268 (0.37%) 
Gastric dilatation  1  1/266 (0.38%)  1/268 (0.37%) 
Gastritis  1  2/266 (0.75%)  0/268 (0.00%) 
Gastrointestinal disorder  1  2/266 (0.75%)  0/268 (0.00%) 
Mouth ulceration  1  1/266 (0.38%)  1/268 (0.37%) 
Regurgitation  1  1/266 (0.38%)  1/268 (0.37%) 
Toothache  1  1/266 (0.38%)  1/268 (0.37%) 
Abnormal faeces  1  0/266 (0.00%)  1/268 (0.37%) 
Dyspepsia  1  0/266 (0.00%)  1/268 (0.37%) 
Eructation  1  1/266 (0.38%)  0/268 (0.00%) 
Gastrooesophageal reflux disease  1  1/266 (0.38%)  0/268 (0.00%) 
Haemorrhoids  1  1/266 (0.38%)  0/268 (0.00%) 
Mallory-Weiss syndrome  1  1/266 (0.38%)  0/268 (0.00%) 
General disorders     
Asthenia  1  2/266 (0.75%)  5/268 (1.87%) 
Fatigue  1  2/266 (0.75%)  5/268 (1.87%) 
Thirst  1  3/266 (1.13%)  4/268 (1.49%) 
Chest discomfort  1  3/266 (1.13%)  2/268 (0.75%) 
Pyrexia  1  2/266 (0.75%)  1/268 (0.37%) 
Chest pain  1  1/266 (0.38%)  1/268 (0.37%) 
Malaise  1  0/266 (0.00%)  2/268 (0.75%) 
Crying  1  0/266 (0.00%)  1/268 (0.37%) 
Discomfort  1  0/266 (0.00%)  1/268 (0.37%) 
Feeling hot  1  0/266 (0.00%)  1/268 (0.37%) 
Hunger  1  0/266 (0.00%)  1/268 (0.37%) 
Ill-defined disorder  1  1/266 (0.38%)  0/268 (0.00%) 
Inflammation  1  0/266 (0.00%)  1/268 (0.37%) 
Pain  1  0/266 (0.00%)  1/268 (0.37%) 
Sensation of foreign body  1  0/266 (0.00%)  1/268 (0.37%) 
Hepatobiliary disorders     
Hepatic function abnormal  1  3/266 (1.13%)  2/268 (0.75%) 
Cholecystitis  1  1/266 (0.38%)  0/268 (0.00%) 
Infections and infestations     
Viral upper respiratory tract infection  1  15/266 (5.64%)  13/268 (4.85%) 
Urinary tract infection  1  3/266 (1.13%)  2/268 (0.75%) 
Upper respiratory tract infection  1  3/266 (1.13%)  1/268 (0.37%) 
Influenza  1  2/266 (0.75%)  1/268 (0.37%) 
Pharyngitis  1  1/266 (0.38%)  1/268 (0.37%) 
Peritonsillitis  1  1/266 (0.38%)  0/268 (0.00%) 
Respiratory tract infection  1  0/266 (0.00%)  1/268 (0.37%) 
Tinea versicolour  1  0/266 (0.00%)  1/268 (0.37%) 
Tonsillitis  1  1/266 (0.38%)  0/268 (0.00%) 
Injury, poisoning and procedural complications     
Muscle strain  1  0/266 (0.00%)  1/268 (0.37%) 
Radius fracture  1  0/266 (0.00%)  1/268 (0.37%) 
Soft tissue injury  1  0/266 (0.00%)  1/268 (0.37%) 
Investigations     
Blood glucose increased  1  1/266 (0.38%)  5/268 (1.87%) 
White blood cell count decreased  1  4/266 (1.50%)  1/268 (0.37%) 
Heart rate increased  1  2/266 (0.75%)  1/268 (0.37%) 
Alanine aminotransferase increased  1  1/266 (0.38%)  1/268 (0.37%) 
Blood bilirubin increased  1  0/266 (0.00%)  2/268 (0.75%) 
Blood pressure increased  1  2/266 (0.75%)  0/268 (0.00%) 
Blood triglycerides increased  1  1/266 (0.38%)  1/268 (0.37%) 
Electrocardiogram T wave abnormal  1  2/266 (0.75%)  0/268 (0.00%) 
Weight increased  1  0/266 (0.00%)  2/268 (0.75%) 
Bilirubin conjugated increased  1  0/266 (0.00%)  1/268 (0.37%) 
Blood cholesterol increased  1  0/266 (0.00%)  1/268 (0.37%) 
Blood creatinine increased  1  0/266 (0.00%)  1/268 (0.37%) 
Blood urea increased  1  0/266 (0.00%)  1/268 (0.37%) 
Blood uric acid increased  1  1/266 (0.38%)  0/268 (0.00%) 
Electrocardiogram QT prolonged  1  0/266 (0.00%)  1/268 (0.37%) 
Electrocardiogram ST-T change  1  1/266 (0.38%)  0/268 (0.00%) 
Electrocardiogram abnormal  1  0/266 (0.00%)  1/268 (0.37%) 
Electrocardiogram high voltage  1  0/266 (0.00%)  1/268 (0.37%) 
Gamma-glutamyltransferase increased  1  0/266 (0.00%)  1/268 (0.37%) 
Hepatic enzyme increased  1  0/266 (0.00%)  1/268 (0.37%) 
Lipids abnormal  1  1/266 (0.38%)  0/268 (0.00%) 
Lipoprotein (a) increased  1  1/266 (0.38%)  0/268 (0.00%) 
Lymphocyte percentage increased  1  0/266 (0.00%)  1/268 (0.37%) 
Neutrophil percentage increased  1  0/266 (0.00%)  1/268 (0.37%) 
Platelet count increased  1  0/266 (0.00%)  1/268 (0.37%) 
Red blood cells urine positive  1  0/266 (0.00%)  1/268 (0.37%) 
Metabolism and nutrition disorders     
Decreased appetite  1  11/266 (4.14%)  15/268 (5.60%) 
Dyslipidaemia  1  1/266 (0.38%)  0/268 (0.00%) 
Hyperlipidaemia  1  0/266 (0.00%)  1/268 (0.37%) 
Hypoproteinaemia  1  1/266 (0.38%)  0/268 (0.00%) 
Musculoskeletal and connective tissue disorders     
Myalgia  1  1/266 (0.38%)  2/268 (0.75%) 
Pain in extremity  1  0/266 (0.00%)  2/268 (0.75%) 
Back pain  1  1/266 (0.38%)  0/268 (0.00%) 
Exostosis  1  1/266 (0.38%)  0/268 (0.00%) 
Fasciitis  1  1/266 (0.38%)  0/268 (0.00%) 
Intervertebral disc protrusion  1  0/266 (0.00%)  1/268 (0.37%) 
Muscle spasms  1  1/266 (0.38%)  0/268 (0.00%) 
Muscle twitching  1  0/266 (0.00%)  1/268 (0.37%) 
Musculoskeletal discomfort  1  1/266 (0.38%)  0/268 (0.00%) 
Neck pain  1  1/266 (0.38%)  0/268 (0.00%) 
Osteoporosis  1  1/266 (0.38%)  0/268 (0.00%) 
Synovitis  1  1/266 (0.38%)  0/268 (0.00%) 
Nervous system disorders     
Dizziness  1  25/266 (9.40%)  23/268 (8.58%) 
Headache  1  20/266 (7.52%)  15/268 (5.60%) 
Somnolence  1  1/266 (0.38%)  13/268 (4.85%) 
Tremor  1  8/266 (3.01%)  2/268 (0.75%) 
Dysgeusia  1  4/266 (1.50%)  2/268 (0.75%) 
Head discomfort  1  2/266 (0.75%)  2/268 (0.75%) 
Paraesthesia  1  2/266 (0.75%)  1/268 (0.37%) 
Poor quality sleep  1  2/266 (0.75%)  1/268 (0.37%) 
Anticholinergic syndrome  1  2/266 (0.75%)  0/268 (0.00%) 
Syncope  1  1/266 (0.38%)  1/268 (0.37%) 
Extrapyramidal disorder  1  1/266 (0.38%)  0/268 (0.00%) 
Head titubation  1  1/266 (0.38%)  0/268 (0.00%) 
Hypersomnia  1  0/266 (0.00%)  1/268 (0.37%) 
Hypertonia  1  0/266 (0.00%)  1/268 (0.37%) 
Hypoaesthesia  1  1/266 (0.38%)  0/268 (0.00%) 
Tension headache  1  1/266 (0.38%)  0/268 (0.00%) 
Psychiatric disorders     
Insomnia  1  6/266 (2.26%)  2/268 (0.75%) 
Anxiety  1  5/266 (1.88%)  1/268 (0.37%) 
Agitation  1  4/266 (1.50%)  1/268 (0.37%) 
Dysphoria  1  2/266 (0.75%)  2/268 (0.75%) 
Initial insomnia  1  2/266 (0.75%)  2/268 (0.75%) 
Hallucination, auditory  1  1/266 (0.38%)  1/268 (0.37%) 
Intentional self-injury  1  1/266 (0.38%)  1/268 (0.37%) 
Sleep disorder  1  1/266 (0.38%)  1/268 (0.37%) 
Abnormal dreams  1  0/266 (0.00%)  1/268 (0.37%) 
Fear  1  0/266 (0.00%)  1/268 (0.37%) 
Irritability  1  1/266 (0.38%)  0/268 (0.00%) 
Libido decreased  1  0/266 (0.00%)  1/268 (0.37%) 
Middle insomnia  1  1/266 (0.38%)  0/268 (0.00%) 
Psychiatric symptom  1  1/266 (0.38%)  0/268 (0.00%) 
Restlessness  1  0/266 (0.00%)  1/268 (0.37%) 
Suicidal ideation  1  1/266 (0.38%)  0/268 (0.00%) 
Suicide attempt  1  0/266 (0.00%)  1/268 (0.37%) 
Renal and urinary disorders     
Dysuria  1  2/266 (0.75%)  1/268 (0.37%) 
Chromaturia  1  0/266 (0.00%)  1/268 (0.37%) 
Nephrolithiasis  1  1/266 (0.38%)  0/268 (0.00%) 
Reproductive system and breast disorders     
Erectile dysfunction  1  3/266 (1.13%)  0/268 (0.00%) 
Menopausal symptoms  1  1/266 (0.38%)  0/268 (0.00%) 
Menstruation irregular  1  0/266 (0.00%)  1/268 (0.37%) 
Prostatitis  1  1/266 (0.38%)  0/268 (0.00%) 
Vaginal haemorrhage  1  0/266 (0.00%)  1/268 (0.37%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  4/266 (1.50%)  0/268 (0.00%) 
Yawning  1  1/266 (0.38%)  3/268 (1.12%) 
Oropharyngeal pain  1  1/266 (0.38%)  1/268 (0.37%) 
Dry throat  1  1/266 (0.38%)  0/268 (0.00%) 
Nasal congestion  1  0/266 (0.00%)  1/268 (0.37%) 
Rhinorrhoea  1  0/266 (0.00%)  1/268 (0.37%) 
Skin and subcutaneous tissue disorders     
Rash  1  9/266 (3.38%)  2/268 (0.75%) 
Hyperhidrosis  1  3/266 (1.13%)  5/268 (1.87%) 
Urticaria  1  3/266 (1.13%)  1/268 (0.37%) 
Alopecia  1  0/266 (0.00%)  2/268 (0.75%) 
Cold sweat  1  0/266 (0.00%)  2/268 (0.75%) 
Night sweats  1  1/266 (0.38%)  1/268 (0.37%) 
Dermatitis  1  1/266 (0.38%)  0/268 (0.00%) 
Eczema  1  0/266 (0.00%)  1/268 (0.37%) 
Pruritus generalised  1  1/266 (0.38%)  0/268 (0.00%) 
Rash maculo-papular  1  1/266 (0.38%)  0/268 (0.00%) 
Vascular disorders     
Hypertension  1  3/266 (1.13%)  2/268 (0.75%) 
Orthostatic hypotension  1  0/266 (0.00%)  1/268 (0.37%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02191397     History of Changes
Other Study ID Numbers: 114589
First Submitted: July 14, 2014
First Posted: July 16, 2014
Results First Submitted: October 9, 2017
Results First Posted: February 18, 2019
Last Update Posted: February 18, 2019