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Trial record 48 of 215 for:    Lamotrigine

Lamotrigine Phase III Study in Bipolar I Disorder

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ClinicalTrials.gov Identifier: NCT01602510
Recruitment Status : Completed
First Posted : May 21, 2012
Results First Posted : January 23, 2017
Last Update Posted : January 23, 2017
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 Bipolar Disorder
Interventions Drug: Lamotrigine
Drug: Placebo
Enrollment 265
Recruitment Details The study consisted of 4 phases: screen phase (<2 weeks[W]), open-label phase (OLP) (Up to 16 W, lamotrigine monotherapy (LM) or combination therapy escalated to a target dose of LM 200 milligrams [mg]/day[D]), randomized double-blind phase (RDP) (up to 36 W, lamotrigine 200 mg/day or placebo) and follow-up visit (14 days after the last dose).
Pre-assignment Details 420 participants entered into OLP and received at least one dose of study medication. Of these 420 participants, 264 were randomized into RDP.
Arm/Group Title Open Label Lamotrigine 200 mg/Day Randomized Placebo Randomized Lamotrigine 200 mg/Day
Hide Arm/Group Description Participants (Par.) received lamotrigine escalated to a target dose of lamotrigine 200mg/day monotherapy for 6 weeks to 16 weeks. If needed, concomitant psychotropic medications were permitted during this phase however medications were discontinued at least 1 week before entering into the double-blind phase. Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks. Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Period Title: Open Label Phase
Started 420 0 0
Completed 117 0 0
Not Completed 303 0 0
Reason Not Completed
Adverse Event             46             0             0
Lack of Efficacy             22             0             0
Protocol Violation             15             0             0
Met protocol-defined stopping criteria             122             0             0
Lost to Follow-up             22             0             0
Physician Decision             19             0             0
Withdrawal by Subject             57             0             0
Period Title: Randomized Phase
Started 0 133 131
Completed 0 59 58
Not Completed 0 74 73
Reason Not Completed
Adverse Event             0             2             6
Lack of Efficacy             0             4             4
Protocol Violation             0             3             3
Met protocol-defined stopping criteria             0             58             48
Lost to Follow-up             0             1             3
Physician Decision             0             0             2
Withdrawal by Subject             0             6             7
Arm/Group Title Open Label Lamotrigine 200 mg/Day
Hide Arm/Group Description Participants (Par.) received lamotrigine escalated to a target dose of lamotrigine 200 mg/day monotherapy for 6 weeks to 16 weeks. If needed, concomitant psychotropic medications were permitted during this phase however medications were discontinued at least 1 week before entering into the double-blind phase.
Overall Number of Baseline Participants 420
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 420 participants
35.7  (11.72)
[1]
Measure Description: Data is presented for Open Label Phase.
Gender   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 420 participants
Female
220
  52.4%
Male
200
  47.6%
[1]
Measure Description: Data is presented for Open Label Phase.
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Not Hispanic or Latino Number Analyzed 420 participants
420
[1]
Measure Description: Data is presented for Open Label Phase.
1.Primary Outcome
Title Time to Intervention for Any Mood Episode (TIME)
Hide Description TIME is defined as being the time from entry into the randomized double-blind phase to the time of the first prescription of any additional pharmacotherapy or Electroconvulsive therapy (ECT) determined by the investigator to be necessary for treatment of a relapse and/or recurrence of a depressive, manic, hypomanic or mixed episode, whichever occurs first. TIME was measured relative to randomization date. Par. prematurely discontinued from the study prior to reaching the TIME event were censored at the time of discontinuation. Analysis was performed using Cox proportional hazards regression model with covariates of site, CGI-S baseline score, treatment and treatment by CGI-S baseline score interaction. The overall hazard ratio for treatment group could not be calculated due to different CGI-S baseline score level.
Time Frame 36 weeks (wks)
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized (RD) Full analysis population: comprised of all randomized par. who took at least one dose of study medication and had at least one post-baseline efficacy/health outcomes assessment during randomized double-blind phase. "NA" implies no data are available. Only those par. with available data at indicated time points were analyzed.
Arm/Group Title Randomized Placebo Randomized Lamotrigine 200 mg/Day
Hide Arm/Group Description:
Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.
Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Overall Number of Participants Analyzed 62 50
Median (95% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
With less than 50% of the Participants got TIME events the median and corresponding 95% confidence interval can not be calculated
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Randomized Placebo, Randomized Lamotrigine 200 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.438
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Hazard Ratio
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.59 to 1.25
Estimation Comments p value with Treatment Group as covariate
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Randomized Placebo, Randomized Lamotrigine 200 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.212
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Hazard Ratio
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.59 to 1.25
Estimation Comments p value with Site as covariate
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Randomized Placebo, Randomized Lamotrigine 200 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.724
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Hazard Ratio
Estimated Value 0.86
Confidence Interval (2-Sided) 95%
0.59 to 1.25
Estimation Comments p value with CGI-S Baseline Score as covariate
2.Secondary Outcome
Title Time to Intervention for Manic, Hypomanic or Mixed Episode (TIMan)
Hide Description TIMan was analyzed using using Cox proportional hazards regression model with covariates of site, CGI-S baseline score, treatment and treatment by CGI-S baseline score interaction. The overall hazard ratio for treatment group could not be calculated due to different CGI-S baseline score level. Par. prematurely discontinued from the study prior to reaching the event were censored at the time of discontinuation.
Time Frame 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
RD Full Analysis Population."NA" implies no data are available. Only those par. with available data at indicated time points were analyzed.
Arm/Group Title Randomized Placebo Randomized Lamotrigine 200 mg/Day
Hide Arm/Group Description:
Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.
Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Overall Number of Participants Analyzed 27 24
Median (95% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
With less than 50% of the Participants got TIMan events the median and corresponding 95% confidence interval can not be calculated
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Randomized Placebo, Randomized Lamotrigine 200 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.869
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Hazard Ratio
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.55 to 1.66
Estimation Comments p value with Treatment Group as covariate
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Randomized Placebo, Randomized Lamotrigine 200 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.061
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Hazard Ratio
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.55 to 1.66
Estimation Comments p value with Site as covariate
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Randomized Placebo, Randomized Lamotrigine 200 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.505
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Hazard Ratio
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.55 to 1.66
Estimation Comments p value with CGI-S Baseline Score as covariate
3.Secondary Outcome
Title Time to Intervention for Depressive Episode (TIDep)
Hide Description TIDep was analyzed using Cox proportional hazards regression model with covariates of site, CGI-S baseline score, treatment and treatment by CGI-S baseline score interaction. The overall hazard ratio for treatment group could not be calculated due to different CGI-S baseline score level. Par. prematurely discontinued from the study prior to reaching the event were censored at the time of discontinuation.
Time Frame 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
RD Full Analysis Population. "NA" implies no data are available. Only those par. with available data at indicated time points were analyzed.
Arm/Group Title Randomized Placebo Randomized Lamotrigine 200 mg/Day
Hide Arm/Group Description:
Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.
Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Overall Number of Participants Analyzed 35 26
Median (95% Confidence Interval)
Unit of Measure: Days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
With less than 50% of the Participants got TIDep events the median and corresponding 95% confidence interval can not be calculated
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Randomized Placebo, Randomized Lamotrigine 200 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.369
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Hazard Ratio
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.48 to 1.32
Estimation Comments p value with Treatment Group as covariate
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Randomized Placebo, Randomized Lamotrigine 200 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.955
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Hazard Ratio
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.48 to 1.32
Estimation Comments p value with Site as covariate
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Randomized Placebo, Randomized Lamotrigine 200 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.874
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Hazard Ratio
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.48 to 1.32
Estimation Comments p value with CGI-S Baseline Score as covariate
4.Secondary Outcome
Title Overall Survival in Study (TIME-SIS).
Hide Description TIME-SIS was defined as the time to intervention (addition of pharmacotherapy or ECT) for any mood episode, or to the time when the participant is withdrawn for any reason after randomization. The premature discontinuation of a participant prior to reaching TIME, for any reason, was treated as an event related to bipolar disorder. All participants prematurely discontinued prior to the TIME event in this analysis were to be assumed to have reached TIME. TIMS-SIS was analyzed using Cox proportional hazards regression model with covariates of site, CGI-S baseline score, treatment and treatment by CGI-S baseline score interaction. The overall hazard ratio for treatment group could not be calculated due to different CGI-S baseline score level. Par. prematurely discontinued from the study prior to reaching the event were censored at the time of discontinuation.
Time Frame 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
RD Full Analysis Population. "NA" implies no data are available. Only those par. with available data at indicated time points were analyzed.
Arm/Group Title Randomized Placebo Randomized Lamotrigine 200 mg/Day
Hide Arm/Group Description:
Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.
Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Overall Number of Participants Analyzed 75 72
Median (95% Confidence Interval)
Unit of Measure: Days
183 [1] 
(140 to NA)
188 [1] 
(117 to NA)
[1]
With less than 50% of the Participants got TIME events the upper bound of 95% confidence interval for median can not be calculated.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Randomized Placebo, Randomized Lamotrigine 200 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.927
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Hazard Ratio
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.73 to 1.40
Estimation Comments p value with Treatment Group as covariate
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Randomized Placebo, Randomized Lamotrigine 200 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.036
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Hazard Ratio
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.73 to 1.40
Estimation Comments p value with Site as covariate
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Randomized Placebo, Randomized Lamotrigine 200 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.509
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Adjusted Hazard Ratio
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.73 to 1.40
Estimation Comments p value with CGI-S Baseline Score as covariate
5.Secondary Outcome
Title Change From Baseline in Clinical Global Impression of Improvements (CGI-I)
Hide Description The CGI-I is a 7-point scale where investigator were asked to assess the participant’s illness at the time of assessment (improved or worsened) relative to a baseline state. In this scale, 1= very much improved; 2= much improved; 3= minimally improved; 4= no change; 5= minimally worse; 6= much worse; or 7= very much worse. Analysis was performed using Analysis of covariance with covariates of site, CGI-S baseline score and treatment. In presented Last-observation-carried-forward datasets, the last non-missing on therapy (OT) score prior to TIME was carried forward to estimate missing data points for the remaining study visits of the treatment period. Baseline value was defined as the last non-missing values at or prior to the randomization. Change from baseline at the time point of interest was calculated by subtracting the baseline values from the individual post-baseline values. If either baseline or post-baseline value was missing, the change from baseline was set to missing.
Time Frame Baseline and up to 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
RD Full Analysis Population.
Arm/Group Title Randomized Placebo Randomized Lamotrigine 200 mg/Day
Hide Arm/Group Description:
Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.
Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Overall Number of Participants Analyzed 133 130
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
2.6  (0.20) 2.7  (0.21)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Randomized Placebo, Randomized Lamotrigine 200 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.833
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-0.4 to 0.5
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in Clinical Global Impression of Severity (CGI-S)
Hide Description The CGI-S is a 7-point scale where investigator were asked to rate the severity of the participant’s illness at the time of assessment on severity of mental illness, where 1= normal, and 7= extremely ill. Data was collected on Weeks 0, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 32 and 36. Analysis performed using Analysis of Covariance (ANCOVA) with covariates of site, CGI-S baseline score (Open label phase), treatment and CGI-S baseline score. In presented Last observation carried forward (LOCF) datasets, last non-missing on therapy score prior to TIME was carried forward to estimate missing data points for remaining study visits of treatment period. The baseline value was defined as last non-missing values at or prior to the randomization. The change from baseline at the time point of interest was calculated by subtracting the baseline values from individual post-baseline values. If either the baseline or post-baseline value was missing, the change from baseline was set to missing as well.
Time Frame Baseline and up to 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
RD Full Analysis Population.
Arm/Group Title Randomized Placebo Randomized Lamotrigine 200 mg/Day
Hide Arm/Group Description:
Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.
Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Overall Number of Participants Analyzed 133 130
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
0.7  (0.15) 0.5  (0.15)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Randomized Placebo, Randomized Lamotrigine 200 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.245
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.2
Confidence Interval (2-Sided) 95%
-0.5 to 0.1
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in Hamilton Depression Rating Scale (HAMD)
Hide Description HAMD consists of 17 items: depressed mood, feelings of guilt, suicide, insomnia-early, middle, late, work and activities, retardation, agitation, anxiety psychic, anxiety somatic, somatic symptoms gastro-intestinal, general somatic symptoms, hypochondriasis, loss of weight, and insight. Investigators rated par. from 0 to 4 (or 2) for these items. Total score is sum of all subscales (0 to 52, higher is worse). Data was collected on Wks 0, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 32, 36. Analysis was performed using ANCOVA with covariates of site, CGI-S baseline (BL) score, treatment and HAMD total BL score. The last non-missing OT score prior to TIME was carried forward to estimate missing data points for remaining study visits of the treatment period. BL value was defined as the last non-missing value at or prior to the randomization. Change from BL was calculated by subtracting BL from the specific post-BL value. If BL or post-BL value was missing, the change from BL was set to missing.
Time Frame Baseline and up to 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
RD Full Analysis Population
Arm/Group Title Randomized Placebo Randomized Lamotrigine 200 mg/Day
Hide Arm/Group Description:
Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.
Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Overall Number of Participants Analyzed 133 130
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
3.0  (0.83) 1.8  (0.84)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Randomized Placebo, Randomized Lamotrigine 200 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.155
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-3.0 to 0.5
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Change From Baseline in Young Mania Rating Scale (YMRS) Total Score
Hide Description YMRS consists of 11 items: Elevated Mood, Increased Motor Activity/Energy, Sexual Interest, Sleep, Irritability, Speech, Language/Thought Disorder, Content, Disruptive/Aggressive Behaviour, Appearance, and Insight. Investigators rated par. from 0 to 4 (or 8) for each of these items. Total score is the sum of all subscales, from 0 to 60 (higher is worse). Data was collected on Wks 0, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 32, 36. Analysis was performed using ANCOVA with covariates of site, CGI-S BL score, treatment and YMRS total BL score. In LOCF datasets, the last non-missing OT score prior to TIME was carried forward to estimate missing data points for the remaining study visits of the treatment period. BL value was defined as the last non-missing values at or prior to the randomization. Change from BL at the time point of interest was calculated by subtracting BL value from the individual post-BL value. If either the BL or post-BL value was missing, change from BL was set to missing.
Time Frame Baseline and up to 36 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
RD Full Analysis Population
Arm/Group Title Randomized Placebo Randomized Lamotrigine 200 mg/Day
Hide Arm/Group Description:
Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.
Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Overall Number of Participants Analyzed 133 130
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
2.4  (0.87) 2.8  (0.88)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Randomized Placebo, Randomized Lamotrigine 200 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.661
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-1.4 to 2.2
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Change From Baseline of Global Assessment Scale (GAS) Total Score
Hide Description For GAS, investigators rated par. for lowest level of functioning during the previous week. The scale has a 10 score categories: 1-10, 11-20, 21-30, 31-40, 41-50, 51-60, 61-70, 71-80, 81-90, 91-100, using intermediary levels when appropriate (from 100 to 1, Lower is worse.). Data was collected on Weeks 0, 1, 2, 3, 4, 6, 8, 12, 16, 20, 24, 32, 36. Analysis was performed using ANCOVA with covariates of site, CGI-S BL score, treatment and GAS total BL score. In presented LOCF datasets, the last non-missing on therapy score prior to TIME was carried forward to estimate missing data points for the remaining study visits of the treatment period. The BL value was defined as the last non-missing values at or prior to the randomization. The change from BL at the time point of interest was calculated by subtracting the BL values from the individual post-BL values. If either the BL or post-BL value was missing, the change from BL was set to missing as well.
Time Frame Baseline and up to 36 weeks
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RD Full Analysis Population
Arm/Group Title Randomized Placebo Randomized Lamotrigine 200 mg/Day
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Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.
Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Overall Number of Participants Analyzed 133 130
Least Squares Mean (Standard Error)
Unit of Measure: Score on a scale
-4.7  (1.75) -4.9  (1.77)
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Statistical Analysis Overview Comparison Group Selection Randomized Placebo, Randomized Lamotrigine 200 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.945
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-3.7 to 3.5
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in Body Weight
Hide Description Participant’s body weight was measured on Weeks 0, 4, 8, 12, 16, 20, 24, 32 and 36. Analysis was performed using ANCOVA with covariates of site, CGI-S baseline score, treatment and baseline body weight. In presented LOCF datasets, the last non-missing on therapy score prior to TIME was carried forward to estimate missing data points for the remaining study visits of the treatment period. The baseline value was defined as the last non-missing values at or prior to the randomization. The change from baseline at the time point of interest was calculated by subtracting the baseline values from the individual post-baseline values. If either the baseline or post-baseline value was missing, the change from baseline was set to missing as well.
Time Frame Baseline and up to 36 weeks.
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RD Full Analysis Population. Only those par. with available data at indicated time points were analyzed.
Arm/Group Title Randomized Placebo Randomized Lamotrigine 200 mg/Day
Hide Arm/Group Description:
Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks.
Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
Overall Number of Participants Analyzed 133 128
Least Squares Mean (Standard Error)
Unit of Measure: Kilograms
-0.72  (0.399) -1.56  (0.407)
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Statistical Analysis Overview Comparison Group Selection Randomized Placebo, Randomized Lamotrigine 200 mg/Day
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.047
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.84
Confidence Interval (2-Sided) 95%
-1.66 to -0.01
Estimation Comments [Not Specified]
Time Frame On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (up to Study Day 230).
Adverse Event Reporting Description On-treatment SAEs and non-serious AEs were reported for the Safety population consisted of all participants who received at least one dose of study drug.
 
Arm/Group Title Randomized Placebo Randomized Lamotrigine 200 mg/Day
Hide Arm/Group Description Participants who reached a stable dose of lamotrigine and met response criteria, defined as a Clinical Global Impression of Severity (CGI-S) score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received placebo for 36 weeks. Participants who reached a stable dose of lamotrigine and met response criteria, defined as a CGI-S score <= 3 maintained for at least 4 continuous weeks and lamotrigine 200 mg/day monotherapy maintained for at least 1 week during open label phase, were enrolled in the double-blind phase of the study. Participants received lamotrigine 200 mg/day for 36 weeks.
All-Cause Mortality
Randomized Placebo Randomized Lamotrigine 200 mg/Day
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Randomized Placebo Randomized Lamotrigine 200 mg/Day
Affected / at Risk (%) Affected / at Risk (%)
Total   3/133 (2.26%)   2/131 (1.53%) 
Injury, poisoning and procedural complications     
Concussion  1  1/133 (0.75%)  0/131 (0.00%) 
Contusion  1  1/133 (0.75%)  0/131 (0.00%) 
Laceration  1  1/133 (0.75%)  0/131 (0.00%) 
Nervous system disorders     
Brain stem infarction  1  0/133 (0.00%)  1/131 (0.76%) 
Psychiatric disorders     
Mania  1  2/133 (1.50%)  0/131 (0.00%) 
Suicide attempt  1  0/133 (0.00%)  1/131 (0.76%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Randomized Placebo Randomized Lamotrigine 200 mg/Day
Affected / at Risk (%) Affected / at Risk (%)
Total   46/133 (34.59%)   40/131 (30.53%) 
Blood and lymphatic system disorders     
Granulocytopenia  1  0/133 (0.00%)  1/131 (0.76%) 
Leukopenia  1  1/133 (0.75%)  0/131 (0.00%) 
Cardiac disorders     
Bundle branch block right  1  1/133 (0.75%)  0/131 (0.00%) 
Myocardial infarction  1  1/133 (0.75%)  0/131 (0.00%) 
Myocardial ischaemia  1  1/133 (0.75%)  0/131 (0.00%) 
Palpitations  1  0/133 (0.00%)  1/131 (0.76%) 
Sinus tachycardia  1  0/133 (0.00%)  1/131 (0.76%) 
Endocrine disorders     
Thyroid disorder  1  1/133 (0.75%)  0/131 (0.00%) 
Eye disorders     
Dry eye  1  0/133 (0.00%)  1/131 (0.76%) 
Vision blurred  1  0/133 (0.00%)  1/131 (0.76%) 
Gastrointestinal disorders     
Diarrhoea  1  2/133 (1.50%)  2/131 (1.53%) 
Nausea  1  1/133 (0.75%)  3/131 (2.29%) 
Abdominal distension  1  1/133 (0.75%)  0/131 (0.00%) 
Abdominal pain  1  1/133 (0.75%)  0/131 (0.00%) 
Chronic gastritis  1  0/133 (0.00%)  1/131 (0.76%) 
Colitis ulcerative  1  1/133 (0.75%)  0/131 (0.00%) 
Constipation  1  1/133 (0.75%)  0/131 (0.00%) 
Dyspepsia  1  0/133 (0.00%)  1/131 (0.76%) 
Gastritis  1  0/133 (0.00%)  1/131 (0.76%) 
Lip ulceration  1  0/133 (0.00%)  1/131 (0.76%) 
Retching  1  0/133 (0.00%)  1/131 (0.76%) 
General disorders     
Fatigue  1  3/133 (2.26%)  2/131 (1.53%) 
Asthenia  1  2/133 (1.50%)  0/131 (0.00%) 
Chest discomfort  1  0/133 (0.00%)  1/131 (0.76%) 
Malaise  1  0/133 (0.00%)  1/131 (0.76%) 
Pain  1  0/133 (0.00%)  1/131 (0.76%) 
Thirst  1  1/133 (0.75%)  0/131 (0.00%) 
Hepatobiliary disorders     
Hepatic function abnormal  1  2/133 (1.50%)  0/131 (0.00%) 
Cholecystitis  1  1/133 (0.75%)  0/131 (0.00%) 
Immune system disorders     
Food allergy  1  1/133 (0.75%)  0/131 (0.00%) 
Infections and infestations     
Nasopharyngitis  1  4/133 (3.01%)  4/131 (3.05%) 
Urinary tract infection  1  4/133 (3.01%)  3/131 (2.29%) 
Upper respiratory tract infection  1  4/133 (3.01%)  2/131 (1.53%) 
Herpes zoster  1  0/133 (0.00%)  1/131 (0.76%) 
Pericoronitis  1  1/133 (0.75%)  0/131 (0.00%) 
Pharyngitis  1  1/133 (0.75%)  0/131 (0.00%) 
Investigations     
Weight decreased  1  1/133 (0.75%)  3/131 (2.29%) 
Alanine aminotransferase increased  1  2/133 (1.50%)  1/131 (0.76%) 
Aspartate aminotransferase increased  1  2/133 (1.50%)  1/131 (0.76%) 
Blood creatine phosphokinase increased  1  1/133 (0.75%)  2/131 (1.53%) 
Blood glucose increased  1  2/133 (1.50%)  1/131 (0.76%) 
Blood pressure increased  1  2/133 (1.50%)  1/131 (0.76%) 
Blood triglycerides increased  1  2/133 (1.50%)  0/131 (0.00%) 
Blood uric acid increased  1  2/133 (1.50%)  0/131 (0.00%) 
Gamma-glutamyltransferase increased  1  1/133 (0.75%)  1/131 (0.76%) 
Weight increased  1  2/133 (1.50%)  0/131 (0.00%) 
Bilirubin conjugated increased  1  0/133 (0.00%)  1/131 (0.76%) 
Blood bilirubin increased  1  0/133 (0.00%)  1/131 (0.76%) 
Blood phosphorus increased  1  0/133 (0.00%)  1/131 (0.76%) 
Blood urine present  1  0/133 (0.00%)  1/131 (0.76%) 
Electrocardiogram ST segment abnormal  1  0/133 (0.00%)  1/131 (0.76%) 
Electrocardiogram T wave abnormal  1  1/133 (0.75%)  0/131 (0.00%) 
Electrocardiogram abnormal  1  0/133 (0.00%)  1/131 (0.76%) 
Heart rate decreased  1  0/133 (0.00%)  1/131 (0.76%) 
Heart rate increased  1  1/133 (0.75%)  0/131 (0.00%) 
Neutrophil count increased  1  1/133 (0.75%)  0/131 (0.00%) 
Specific gravity urine increased  1  0/133 (0.00%)  1/131 (0.76%) 
Urine ketone body present  1  0/133 (0.00%)  1/131 (0.76%) 
White blood cell count increased  1  1/133 (0.75%)  0/131 (0.00%) 
Metabolism and nutrition disorders     
Hyperglycaemia  1  2/133 (1.50%)  1/131 (0.76%) 
Gout  1  1/133 (0.75%)  0/131 (0.00%) 
Hypokalaemia  1  1/133 (0.75%)  0/131 (0.00%) 
Nervous system disorders     
Headache  1  4/133 (3.01%)  4/131 (3.05%) 
Poor quality sleep  1  4/133 (3.01%)  2/131 (1.53%) 
Dizziness  1  1/133 (0.75%)  2/131 (1.53%) 
Somnolence  1  1/133 (0.75%)  1/131 (0.76%) 
Hypoaesthesia  1  1/133 (0.75%)  0/131 (0.00%) 
Psychiatric disorders     
Depressed mood  1  2/133 (1.50%)  1/131 (0.76%) 
Insomnia  1  2/133 (1.50%)  1/131 (0.76%) 
Affect lability  1  1/133 (0.75%)  0/131 (0.00%) 
Agitation  1  0/133 (0.00%)  1/131 (0.76%) 
Anxiety  1  0/133 (0.00%)  1/131 (0.76%) 
Emotional distress  1  1/133 (0.75%)  0/131 (0.00%) 
Hyposomnia  1  0/133 (0.00%)  1/131 (0.76%) 
Initial insomnia  1  1/133 (0.75%)  0/131 (0.00%) 
Irritability  1  1/133 (0.75%)  0/131 (0.00%) 
Listless  1  1/133 (0.75%)  0/131 (0.00%) 
Sleep disorder  1  0/133 (0.00%)  1/131 (0.76%) 
Suicidal ideation  1  1/133 (0.75%)  0/131 (0.00%) 
Renal and urinary disorders     
Nephrolithiasis  1  0/133 (0.00%)  1/131 (0.76%) 
Pollakiuria  1  1/133 (0.75%)  0/131 (0.00%) 
Reproductive system and breast disorders     
Menstrual disorder  1  0/133 (0.00%)  1/131 (0.76%) 
Skin and subcutaneous tissue disorders     
Rash  1  2/133 (1.50%)  2/131 (1.53%) 
Alopecia  1  0/133 (0.00%)  1/131 (0.76%) 
Skin mass  1  0/133 (0.00%)  1/131 (0.76%) 
Swelling face  1  0/133 (0.00%)  1/131 (0.76%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
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
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Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01602510     History of Changes
Other Study ID Numbers: 113783
First Submitted: May 17, 2012
First Posted: May 21, 2012
Results First Submitted: September 19, 2016
Results First Posted: January 23, 2017
Last Update Posted: January 23, 2017