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Trial record 77 of 215 for:    Lamotrigine

A Phase IV Study of the Safety and Efficacy of Aripiprazole in Combination With Lamotrigine in the Long-Term Maintenance Treatment of Patients With Bipolar I Disorder With A Recent Manic or Mixed Episode

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00277212
Recruitment Status : Completed
First Posted : January 16, 2006
Results First Posted : October 20, 2010
Last Update Posted : December 2, 2013
Sponsor:
Collaborator:
Otsuka America Pharmaceutical
Information provided by:
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Bipolar Disorder
Interventions Drug: Lamotrigine + Aripiprazole
Drug: Lamotrigine + Placebo
Enrollment 1169
Recruitment Details  
Pre-assignment Details A total of 1169 patients were enrolled in the study; 382 participants were considered baseline failures and did not enter Phase 1.
Arm/Group Title Phase 1: Single-Blind Treatment, Lamotrigine + Aripiprazole Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Hide Arm/Group Description Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 1 (all subjects) - up to 24 weeks Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
Period Title: Phase 1 - Single-Blind Treatment
Started 787 0 0
Phase 1 Safety Sample 787 0 0
Phase 1 Efficacy Sample 756 0 0
Completed 352 0 0
Not Completed 435 0 0
Reason Not Completed
Lack of Efficacy             61             0             0
Adverse Event             93             0             0
Withdrawal by Subject             96             0             0
Lost to Follow-up             87             0             0
Poor/Noncompliance             35             0             0
Pregnancy             6             0             0
Subject No Longer Met Study Criteria             44             0             0
Administrative Reason by Sponsor             1             0             0
Other Reasons             12             0             0
Period Title: Phase 2 - Double-Blind Treatment
Started 0 173 178 [1]
Phase 2 Safety Sample 0 165 176
Phase 2 Efficacy Sample 0 164 174
Completed 0 53 65
Not Completed 0 120 113
Reason Not Completed
Lack of Efficacy             0             54             39
Adverse Event             0             10             16
Withdrawal by Subject             0             17             16
Lost to Follow-up             0             18             18
Poor/Noncompliance             0             7             8
Pregnancy             0             2             2
Subject No Longer Meets Study Criteria             0             4             6
Administrative Reasons By Sponsor             0             1             3
Other reasons             0             7             5
[1]
1 participant did not want to continue in the study for personal reasons, and did not enter Phase 2.
Arm/Group Title Phase 1: Single-Blind Treatment, Lamotrigine + Aripiprazole
Hide Arm/Group Description Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 1 (all subjects) - up to 24 weeks
Overall Number of Baseline Participants 796
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 796 participants
38.1  (12.0)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 796 participants
Female
505
  63.4%
Male
291
  36.6%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 796 participants
White 693
Black/African American 88
Asian 10
American Indian/Alaska Native 2
Native Hawaiian/Other Pacific Islander 1
Other 2
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 796 participants
Hispanic or Latino 93
Not Hispanic or Latino 703
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 796 participants
29.7  (7.6)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 796 participants
84.7  (22.7)
BMI Category  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 796 participants
18.5 <= BMI <25 221
25 <= BMI <30 215
BMI <18.5 12
BMI >=30 321
Missing 27
1.Primary Outcome
Title Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2)
Hide Description Time from randomization to relapse to a manic or mixed episode in the Double-Blind Relapse Assessment Phase as measured by the Proportion of Participants without Relapse Through Week 52 (Kaplan-Meier's estimated survival rate).
Time Frame Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized Participants (comprises all patients who are randomized in Phase 2). n= number of randomized participants evaluated at given time point.
Arm/Group Title Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Hide Arm/Group Description:
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
Overall Number of Participants Analyzed 173 178
Measure Type: Number
Unit of Measure: Proportion of Participants
Week 0 (n=173, n=178) 1.00 1.00
Week 2 (n=162, n=172) 0.98 0.98
Week 4 (n=154, n=159) 0.97 0.96
Week 6 (n=142, n=147) 0.95 0.93
Week 8 (n=135, n=135) 0.93 0.90
Week 12 (n=121, n=127) 0.89 0.90
Week 16 (n=101, n=127) 0.88 0.90
Week 20 (n=94, n=127) 0.88 0.90
Week 24 (n=86, n=127) 0.84 0.90
Week 28 (n=79, n=127) 0.81 0.90
Week 32 (n=69, n=83) 0.78 0.89
Week 36 (n=67, n=83) 0.78 0.89
Week 40 (n=62, n=83) 0.77 0.89
Week 44 (n=62, n=83) 0.77 0.89
Week 48 (n=62, n=83) 0.77 0.89
Week 52 (n=62, n=83) 0.77 0.89
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.058
Comments stratified Log-Rank test, controlling for type of index mood episode
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.552
Confidence Interval (2-Sided) 95%
0.296 to 1.030
Estimation Comments Cox's proportional hazards model, with type of index modd episode as stratification factor, and randomized treatment group as covariate.
2.Secondary Outcome
Title Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2
Hide Description Proportion of Participants without Relapse Through Week 52 (Kaplan-Meier's estimated survival rate).
Time Frame Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized Participants (comprises all patients who are randomized in Phase 2). n= number of randomized participants evaluated at given time point.
Arm/Group Title Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Hide Arm/Group Description:
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
Overall Number of Participants Analyzed 173 178
Measure Type: Number
Unit of Measure: Proportion of Participants
Week 0 (n=173, n=178) 1.00 1.00
Week 2 (n=163, n=175) 0.96 0.95
Week 4 (n=154, n=160) 0.91 0.91
Week 6 (n=145, n=149) 0.87 0.88
Week 8 (n=135, n=136) 0.83 0.84
Week 12 (n=121, n=123) 0.76 0.82
Week 16 (n=102, n=113) 0.75 0.80
Week 20 (n=94, n=111) 0.74 0.80
Week 24 (n=91, n=95) 0.69 0.78
Week 28 (n=78, n=85) 0.65 0.77
Week 32 (n=69, n=83) 0.62 0.75
Week 36 (n=67, n=76) 0.62 0.74
Week 40 (n=62, n=70) 0.61 0.73
Week 44 (n=62, n=70) 0.61 0.73
Week 48 (n=62, n=70) 0.61 0.73
Week 52 (n=19, n=70) 0.58 0.73
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.055
Comments p-value for equality of survival curves
Method Log Rank
Comments stratified log-rank test, controlling for type of index mood episode
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.671
Confidence Interval (2-Sided) 95%
0.446 to 1.011
Estimation Comments aripiprazole/placebo; Cox's proportional hazards model, with type of index mood episode as stratification facto, and randomized treatment group as covariate.
3.Secondary Outcome
Title Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2)
Hide Description Proportion of Participants without Relapse Through Week 52 (Kaplan-Meier's estimated survival rate).
Time Frame Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized Participants (comprises all patients who are randomized in Phase 2). n= number of randomized participants evaluated at given time point.
Arm/Group Title Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Hide Arm/Group Description:
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
Overall Number of Participants Analyzed 173 178
Measure Type: Number
Unit of Measure: Proportion of Participants
Week 0 (n=173, n=178) 1.00 1.00
Week 2 (n=163, n=175) 0.98 0.98
Week 4 (n=151, n=160) 0.94 0.95
Week 6 (n=145, n=149) 0.91 0.94
Week 8 (n=132, n=136) 0.89 0.93
Week 12 (n=119, n=123) 0.85 0.90
Week 16 (n=102, n=113) 0.84 0.89
Week 20 (n=102, n=111) 0.84 0.89
Week 24 (n=91, n=95) 0.82 0.87
Week 28 (n=79, n=85) 0.79 0.85
Week 32 (n=74, n=82) 0.79 0.84
Week 36 (n=74, n=76) 0.79 0.83
Week 40 (n=74, n=70) 0.79 0.82
Week 44 (n=74, n=70) 0.79 0.82
Week 48 (n=74, n=70) 0.79 0.82
Week 52 (n=19, n=70) 0.76 0.82
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.381
Comments p-value for equality of survival curves
Method Log Rank
Comments stratified log-rank test, conrolling for type of index mood episode
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.784
Confidence Interval (2-Sided) 95%
0.454 to 1.354
Estimation Comments aripiprazole/placebo; Cox's proportional hazards model, with type of index mood episode as stratification facto, and randomized treatment group as covariate.
4.Secondary Outcome
Title Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2)
Hide Description Proportion of Participants without Discontinuation Through Week 52(Kaplan-Meier's estimated survival rate).
Time Frame Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Hide Outcome Measure Data
Hide Analysis Population Description
Randomized Participants (comprises all patients who are randomized in Phase 2). n= number of randomized participants evaluated at given time point.
Arm/Group Title Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Hide Arm/Group Description:
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
Overall Number of Participants Analyzed 173 178
Measure Type: Number
Unit of Measure: Proportion of Participants
Week 0 (n=173, n=178) 0.95 0.99
Week 2 (n=164, n=175) 0.90 0.91
Week 4 (n=155, n=161) 0.84 0.84
Week 6 (n=145, n=149) 0.79 0.78
Week 8 (n=135, n=138) 0.71 0.70
Week 12 (n=122, n=124) 0.61 0.65
Week 16 (n=103, n=115) 0.55 0.62
Week 20 (n=95, n=110) 0.53 0.59
Week 24 (n=90, n=104) 0.46 0.51
Week 28 (n=78, n=89) 0.41 0.47
Week 32 (n=70, n=83) 0.38 0.44
Week 36 (n=64, n=77) 0.36 0.41
Week 40 (n=61, n=72) 0.34 0.39
Week 44 (n=57, n=69) 0.33 0.38
Week 48 (n=56, n=66) 0.32 0.37
Week 52 (n=19, n=65) 0.25 0.37
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.295
Comments p-value for equality of survival curves
Method Log Rank
Comments stratified Log-Rank Test, controlling for type of index mood episode
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.871
Confidence Interval (2-Sided) 95%
0.672 to 1.128
Estimation Comments aripiprazole/placebo; Cox's proportional hazards model, with type of index mood episode as stratification facto, and randomized treatment group as covariate.
5.Secondary Outcome
Title Deaths, Treatment-Emergent Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Discontinuation of Study Medication, Treatment-Emergent AEs and Treatment-Emergent Extrapyramidal Syndrome (EPS)-Related AEs
Hide Description AE is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a cancer, is a congenital anomaly/birth defect, results in the development of drug dependency or drug abuse, is an important medical event.
Time Frame Throughout Phase 2 (up to 52 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
The Phase 2 Safety Sample comprises all patients who are randomized into Phase 2 and take at least one dose of double-blind medication in Phase 2, as indicated on the study therapy form.
Arm/Group Title Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Hide Arm/Group Description:
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
Overall Number of Participants Analyzed 165 176
Measure Type: Number
Unit of Measure: participants
Deaths 0 0
Treatment-Emergent SAEs 9 5
Suicide-Related SAEs 0 0
AEs Leading to Discontinuation of Study Medication 12 14
Treatment-Emergent AEs 111 124
Treatment-Emergent EPS-Related AEs 15 28
6.Secondary Outcome
Title Adjusted Mean Change From Baseline in Body Weight, Phase 2
Hide Description Adjusted for index mood episode and baseline assessment
Time Frame Baseline, Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from the phase 2 Safety Sample who had body weight evaluation at baseline and week 52 LOCF.
Arm/Group Title Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Hide Arm/Group Description:
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
Overall Number of Participants Analyzed 143 151
Mean (Standard Error)
Unit of Measure: kg
-1.81  (0.48) 0.43  (0.47)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Week 52 LOCF
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments ANOVA (main effects=double-blind treatment, covariate=index mood episode) used for baseline comparisons. ANCOVA (main effects=double-blind treatment, covariates=index mood episode & baseline assessment) used for mean change from baseline comparisons
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Treatement Difference
Estimated Value 2.24
Confidence Interval (2-Sided) 95%
0.91 to 3.57
Estimation Comments Aripiprazole vs. placebo
7.Secondary Outcome
Title Number of Participants Showing Clinically Relevant Weight Loss by Study Week
Hide Description Weight Loss of at least a 7% decrease from Baseline.
Time Frame Weeks 12, 24, 36, 52
Hide Outcome Measure Data
Hide Analysis Population Description
Observed cases (OC) data set (actual observation at each visit), Last observation carried forward (LOCF) data set (data recorded at a given visit or, if no observation is recorded at that visit, data carried forward from the previous visit), and Overall, Phase 2 Safety Sample; n=number assessed at given time point.
Arm/Group Title Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Hide Arm/Group Description:
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
Overall Number of Participants Analyzed 165 176
Measure Type: Number
Unit of Measure: Participants
Week 12 (n=105, 107) 7 9
Week 24 (n=84, 87) 8 9
Week 36 (n=54, 67) 10 6
Week 52 (n=49, 56) 10 6
Week 52 LOCF (n=143, 151) 22 13
At Any Time (n=147, 154) 26 19
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Week 52 LOCF
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.073
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.56
Confidence Interval (2-Sided) 95%
0.29 to 1.07
Estimation Comments aripiprazole/placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments At Any Time
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.194
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
8.Secondary Outcome
Title Number of Participants Showing Clinically Relevant Weight Gain by Study Week
Hide Description Weight gain of at least a 7% increase from Baseline.
Time Frame Weeks 12, 24, 36, 52
Hide Outcome Measure Data
Hide Analysis Population Description
Observed cases (OC) data set (actual observation at each visit), Last observation carried forward (LOCF) data set (data recorded at a given visit or, if no observation is recorded at that visit, data carried forward from the previous visit), and Overall, Phase 2 Safety Sample; n=number assessed at given time point.
Arm/Group Title Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Hide Arm/Group Description:
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
Overall Number of Participants Analyzed 165 176
Measure Type: Number
Unit of Measure: Participants
Week 12 (n=105, 107) 2 4
Week 24 (n=84, 87) 3 10
Week 36 (n=54, 67) 5 14
Week 52 (n=49, 56) 2 7
Week 52 LOCF (n=143, 151) 5 18
At Any Time (n=147, 154) 8 27
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Week 52 LOCF
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter relative risk
Estimated Value 3.41
Confidence Interval (2-Sided) 95%
1.30 to 8.94
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
9.Secondary Outcome
Title Adjusted Mean Change From Baseline in BMI by Study Week
Hide Description Adjusted for index mood episode and baseline assessment.
Time Frame Baseline, Weeks 12, 24, 36, 52
Hide Outcome Measure Data
Hide Analysis Population Description
Observed cases (OC) data set (actual observation at each visit), Last observation carried forward (LOCF) data set (data recorded at a given visit or, if no observation is recorded at that visit, data carried forward from the previous visit), and Overall, Phase 2 Safety Sample; n=number assessed at given time point.
Arm/Group Title Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Hide Arm/Group Description:
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
Overall Number of Participants Analyzed 165 176
Mean (Standard Error)
Unit of Measure: kg/m2
Baseline (n=143, 150) 30.77  (0.63) 30.13  (0.61)
Change from Baseline Week 12 (n=105, 107) -0.39  (0.15) -0.03  (0.15)
Change from Baseline Week 24 (n=84, 87) -0.60  (0.20) 0.14  (0.20)
Change from Baseline Week 36 (n=54, 67) -0.63  (0.33) 0.34  (0.30)
Change from Baseline Week 52 (n=49, 56) -0.73  (0.37) 0.19  (0.34)
Change from Baseline Week 52 LOCF (n=143, 150) -0.62  (0.17) 0.17  (0.17)
Highest Change from Baseline (n=143, 150) -0.02  (0.15) 0.61  (0.14)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.467
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA model, with double-blind treatment as main effects and index mood episode as covariate, is used for Baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.64
Confidence Interval (2-Sided) 95%
-2.37 to 1.09
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from Baseline at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariates=index mood episode & baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.36
Confidence Interval (2-Sided) 95%
-0.06 to 0.78
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariates=index mood episode & baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.19 to 1.30
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from baseline at Week 36
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariates=index mood episode & baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.08 to 1.86
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from baseline at Week 52
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariates=index mood episode & baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
-0.08 to 1.92
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from baseline at Week 52 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariates=index mood episode & baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.31 to 1.26
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Highest Change from baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariates=index mood episode & baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.63
Confidence Interval (2-Sided) 95%
0.23 to 1.04
Estimation Comments aripiprazole - placebo
10.Secondary Outcome
Title Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
Hide Description Abbreviations and further description used in table: Sinus tachycardia, ≥120 beats per minute (bpm) and ↑ ≥15 bpm & no current diagnosis of supraventricular or ventricular tachycardia/atrial fibrillation (AF)/atrial flutter/ other rhythm abnormality. Sinus bradycardia, ≤ 50 bpm and ↓ 15 bpm & no current diagnosis of AF/atrial flutter/other rhythm abnormality. Supraventricular premature beat (SPB), Ventricular premature beat (VPB), Atroventricular (A-V). Other intraventricular block, QRS ≥0.12 sec and ↑ ≥0.02 sec & no current diagnosis of left or right bundle branch block.
Time Frame Throughout the study, up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with ECG evaluation from the phase 2 Safety Sample (all patients who are randomized into Phase 2 and take at least one dose of double-blind medication in Phase 2, as indicated on the study therapy form.)
Arm/Group Title Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Hide Arm/Group Description:
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
Overall Number of Participants Analyzed 124 132
Measure Type: Number
Unit of Measure: particiapnts
Tachycardia: ≥ 120 bpm and ↑ ≥ 15 bpm 1 1
Bradycardia: ≤ 50 bpm and ↓ 15 bpm 2 0
Sinus Tachycardia: ≥ 120 bpm and ↑ ≥ 15 bpm 1 0
Sinus Bradycardia: ≤ 50 bpm and ↓ 15 bpm 2 0
SPB: not present → present (see description) 0 0
VPB: not present → present (see description) 2 1
Supraventricular Tachycardia: not present→ present 0 0
Ventricular Tachycardia: not present → present 0 0
Atrial Fibrillation (AF): not present → present 0 0
AF With Rapid Ventricular Response 0 0
Atrial Flutter: not present → present 0 1
1st Degree A-V Block: PR ≥0.20 sec and ↑ ≥0.05 sec 0 0
2nd Degree A-V Block: not present → present 0 0
3rd Degree A-V Block: not present → present 0 0
Left Bundle Branch Block: not present → present 0 0
Right Bundle Branch Block: not present → present 6 4
Pre-excitation Syndrome: not present → present 0 0
Other Intraventricular Conduction: see description 0 0
Acute Infarction: not present → present 0 0
Subacute (recent) Infarction: not present→ present 0 0
Old Infarction: not present → present 1 0
Myocardial Ischemia: not present → present 0 0
Symmetrical T-Wave Inversions: not present→present 0 0
QTc Bazett: > 450 msec 5 6
QTc (.37): > 450 msec 0 0
QTc (.33): > 450 msec 0 1
11.Secondary Outcome
Title Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment
Hide Description In order to be identified as clinically relevant abnormal, an on-drug value must meet the Criterion Value (CV) and also represent a change from the patient’s pretreatment value of at least the Change Relative to Baseline (CRB) magnitude. Heart Rate CV: 120 beats per minute (bpm), CRB: increase of ≥15 / CV: 50 bpm, CRB: decrease of ≥15. Systolic BP CV: 180 mmHg, CRB: increase of ≥20 / CV: 90 mmHg, CRB: decrease of ≥20. Diastolic BP CV: 105 mmHg, CRB: increase of ≥15 / CV: 50 mmHg, CRB: decrease of ≥15.
Time Frame Up to 52 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2 Safety Sample (all patients who are randomized into Phase 2 and take at least one dose of double-blind medication in Phase 2, as indicated on the study therapy form).
Arm/Group Title Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Hide Arm/Group Description:
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
Overall Number of Participants Analyzed 165 176
Measure Type: Number
Unit of Measure: participants
Systolic BP, supine-Increase (n=160,168) 3 1
Systolic BP, supine-Decrease (n=160,168) 7 5
Systolic BP, standing-Increase (n=153, 157) 3 0
Systolic BP, standing-Decrease (n=153,157) 2 4
Diastolic BP, supine-Increase (n=160,168) 2 0
Diastolic BP, supine-Decrease (n=160,168) 0 3
Diastolic BP, standing-Increase (n=153,157) 6 1
Diastolic BP, standing-Decrease (n=153,157) 0 1
Heart Rate, supine-Increase (n=160,168) 0 0
Heart Rate, supine-Decrease (n=160,168) 3 0
Heart Rate, standing-Increase (n=153, 157) 4 2
Heart Rate, standing-Decrease (n=153, 157) 1 0
12.Secondary Outcome
Title Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
Hide Description Chemistry, hematology, and urinalysis abnormalities.Abbreviations used: alanine aminotransferase (ALT), institutional upper limit of normal (ULN), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), baseline (BL)
Time Frame Throughout Phase 2 of the study, up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2 safety sample
Arm/Group Title Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Hide Arm/Group Description:
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
Overall Number of Participants Analyzed 165 176
Measure Type: Number
Unit of Measure: particiapnts
ALT ≥3 x ULN (n=151,157) 3 0
AST ≥3 x ULN (n=151, 157) 2 1
ALP ≥3 x ULN (n=151, 157) 0 0
LDH ≥3 x ULN (n=151, 158) 0 0
BUN ≥30 mg/dL (n=151, 158) 0 2
Creatine kinase (n=3, 1) 0 0
Creatinine ≥2.0 mg/dL (n=151, 157) 0 0
Uric acid (n=151, 157) 0 2
Bilirubin (total) ≥ 2.0 mg/dL (n=152, 157) 0 0
Prolactin (n=152, 158) 32 18
Cholesterol Total (n=151, 157) 22 28
Cholesterol Total (fasting) (n=126, 124) 17 25
Cholesterol Total (non-fasting) (n=68, 75) 9 7
Glucose Fasting Serum (n=126, 125) 15 13
HDL-C (n=151, 158) 53 38
HDL-C (fasting) (n=126, 125) 44 25
HDL-C (non-fasting) (n=68, 75) 23 19
LDL-C (n=151, 157) 17 26
LDL-C (fasting) (n=126, 124) 14 22
LDL-C (non-fasting) (n=68, 75) 7 5
Triglycerides (n=151, 157) 0 0
Triglycerides (fasting) (n=126, 124) 26 29
Triglycerides (non-fasting) (n=68, 75) 19 20
Sodium serum (n=152, 158) 1 0
Potassium serum (n=152, 158) 0 0
Chloride serum (n=152, 158) 0 0
Calcium (n=151, 157) 0 0
Hemoglobin ≤11.5 g/dL(m)/≤9.5 g/dL(f) (n=152, 156) 1 0
Hematocrit ≤37(m)/≤32(f) & 3 ↓from BL (n=152,156) 1 3
Leukocytes ≤2800 mm^3 or ≥16000 mm^3 (n=152, 156) 0 2
Eosinophils relative (calculated)≥10% (n=152, 156) 2 2
Neutrophils relative (calculated)≤15% (n=152, 156) 0 0
Platelets ≤75,000 mm3 or ≥700,000 mm3 (n=152,155) 0 0
Protein urine increase of ≥2 units (n=145, 152) 0 0
Glucose urine (n=149, 155) 0 0
13.Secondary Outcome
Title Summary of Concomitant Medications, Phase 1
Hide Description [Not Specified]
Time Frame Phase 1 (9 to 24 Week Single-blind Stabilization Phase)
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 1 Safety Sample (all patients who take at least one dose of singleblind aripiprazole in Phase 1, as indicated on the study therapy form).
Arm/Group Title Phase 1: Single-Blind Treatment, Lamotrigine + Aripiprazole
Hide Arm/Group Description:
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 1 (all subjects) - up to 24 weeks
Overall Number of Participants Analyzed 787
Measure Type: Number
Unit of Measure: participants
Any central nervous system Medication 550
Analgesic 2
Anesthetic, general 1
Anesthetic, local 3
Anticholinergic 98
Antidepressant 12
Antiepileptic 48
Antimigraine prep 12
Antipsychotic 20
Anxiolytic 267
Hypnotic & Sedative 206
Opiod 78
Other Analgesic & Antipyretic 253
Other Nervous System Drug 1
Psychostimulant 2
Any extrapyramidal syndrome Medication 98
Benztropine 98
14.Secondary Outcome
Title Summary of Concomitant Medications, Phase 2
Hide Description [Not Specified]
Time Frame Phase 2 (52 Week Double-blind Relapse Assessment Phase)
Hide Outcome Measure Data
Hide Analysis Population Description
Phase 2 Safety Sample (all patients who are randomized into Phase 2 and take at least one dose of double-blind medication in Phase 2, as indicated on the study therapy form).
Arm/Group Title Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Hide Arm/Group Description:
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
Overall Number of Participants Analyzed 165 176
Measure Type: Number
Unit of Measure: participants
Any central nervous system Medication 120 132
Anesthetic, local 1 0
Anticholinergic 21 25
Antidepressant 3 1
Antiepileptic 8 11
Antimigraine prep 1 3
Antipsychotic 5 3
Anxiolytic 63 62
Hypnotic & Sedative 50 41
Opiod 20 14
Other Analgesic & Antipyretic 53 66
Psychostimulant 0 1
Any extrapyramidal syndrome Medication 25 35
Benztropine 25 35
Trihexyphenidyl 1 1
15.Secondary Outcome
Title Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score
Hide Description The SAS is a 10-item instrument used to evaluate the presence and severity of parkinsonian symptomatology. The ten items focus on rigidity rather than bradykinesia, and do not assess subjective rigidity or slowness. Items are rated for severity on a 0-4 scale, with definitions given for each anchor point. The total SAS Score has a possible range from 10 to 50. Negative change scores indicate improvement.
Time Frame Baseline, Weeks 8, 24, 36, 52
Hide Outcome Measure Data
Hide Analysis Population Description
Observed cases (OC) data set (actual observation at each visit), Last observation carried forward (LOCF) data set (data recorded at a given visit or, if no observation is recorded at that visit, data carried forward from the previous visit). n=number of participants analyzed at timepoint.
Arm/Group Title Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Hide Arm/Group Description:
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
Overall Number of Participants Analyzed 165 176
Mean (Standard Error)
Unit of Measure: units on a scale
Baseline (n=125, 128) 10.59  (0.12) 10.58  (0.12)
Change from Baseline at Week 8 (n=125, 124) -0.20  (0.10) 0.05  (0.10)
Change from Baseline at Week 24 (n=85, 89) -0.21  (0.13) 0.03  (0.13)
Change from Baseline at Week 36 (n=54, 67) -0.38  (0.11) -0.14  (0.10)
Change from Baseline at Week 52 (n=50, 56) -0.35  (0.13) -0.05  (0.12)
Change from Baseline at Week 52 LOCF (n=152, 161) -0.22  (0.10) 0.02  (0.10)
Highest Change from Baseline (n=152, 161) 0.03  (0.12) 0.34  (0.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.971
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANOVA
Comments ANOVA model, with double-blind treatment as main effects, is used for Baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.35 to 0.34
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from baseline at Week 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariate=baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.24
Confidence Interval (2-Sided) 95%
-0.03 to 0.51
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariate=baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.24
Confidence Interval (2-Sided) 95%
-0.13 to 0.60
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from Baseline at Week 36
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariate=baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
-0.06 to 0.55
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from baseline at Week 52
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariate=baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
-0.06 to 0.65
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from Baseline at Week 52 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.095
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariate=baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.24
Confidence Interval (2-Sided) 95%
-0.04 to 0.52
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Highest change from Baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.061
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariate=baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.31
Confidence Interval (2-Sided) 95%
-0.01 to 0.63
Estimation Comments aripirazole - placebo
16.Secondary Outcome
Title Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score
Hide Description The AIMS is an assessment of movement dysfunctions. It is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs and 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in 3 main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe). The AIMS Total Score has a possible range from 0 to 28. Negative change scores indicate improvement in movement dysfunction.
Time Frame Baseline, Weeks 8, 24, 36, 52
Hide Outcome Measure Data
Hide Analysis Population Description
Observed cases (OC) data set (actual observation at each visit), Last observation carried forward (LOCF) data set (data recorded at a given visit or, if no observation is recorded at that visit, data carried forward from the previous visit). n=number of participants analyzed at timepoint.
Arm/Group Title Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Hide Arm/Group Description:
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
Overall Number of Participants Analyzed 165 176
Mean (Standard Error)
Unit of Measure: units on a scale
Baseline (n=125, 128) 0.21  (0.07) 0.14  (0.07)
Change from Baseline at Week 8 (n=124, 124) -0.05  (0.05) 0.06  (0.06)
Change from Baseline at Week 24 (n=85, 89) -0.01  (0.06) 0.04  (0.05)
Change from Baseline at Week 36 (n=54, 67) -0.09  (0.08) 0.13  (0.07)
Change from Baseline at Week 52 (n=50, 56) -0.11  (0.04) -0.05  (0.04)
Change from Baseline at Week 52 LOCF (n=153, 161) 0.05  (0.06) -0.01  (0.06)
Highest Change from Baseline (n=153, 161) 0.10  (0.07) 0.14  (0.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.458
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANOVA
Comments ANOVA model, controlling for treatment, is used for baseline estimates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.07
Confidence Interval 95%
-0.25 to 0.11
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from Baseline at Week 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariate=baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
-0.05 to 0.26
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariate=baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
-0.11 to 0.20
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from Baseline at Week 36
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariate=baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.21
Confidence Interval (2-Sided) 95%
0.00 to 0.42
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from Baseline at week 52
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariate=baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.05 to 0.16
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from baseline at Week 52 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.515
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariate=baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.22 to 0.11
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Highest Change from Baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.730
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariate=baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.16 to 0.23
Estimation Comments aripiprazole - placebo
17.Secondary Outcome
Title Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment,
Hide Description The Barnes Akathisia Rating Scale is a 4-item scale to assess presence and severity of drug-induced akathisia, including both objective items and subjective items, together with a global clinical assessment of akathisia. Global assessment is made on a scale of 0 to 5 with comprehensive definitions provided for each anchor point on scale: 0=absent; 1=questionable; 2=mild akathisia; 3=moderate akathisia; 4=marked akathisia; 5=severe akathisia. Score has a possible range from 0 (absent) to 5 (severe akathisia). Negative change scores indicate improvement in akathisia.
Time Frame Baseline, Weeks 8, 24, 36, 52
Hide Outcome Measure Data
Hide Analysis Population Description
Observed cases (OC) data set (actual observation at each visit), Last observation carried forward (LOCF) data set (data recorded at a given visit or, if no observation is recorded at that visit, data carried forward from the previous visit). n=number of participants analyzed at timepoint.
Arm/Group Title Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Hide Arm/Group Description:
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
Overall Number of Participants Analyzed 165 176
Mean (Standard Error)
Unit of Measure: units on a scale
Baseline (n=125, 128) 0.22  (0.05) 0.27  (0.05)
Change from Baseline at Week 8 (n=125, 124) -0.12  (0.05) 0.04  (0.05)
Change from Baseline at Week 24 (n=85, 89) -0.09  (0.05) -0.06  (0.05)
Change from Baseline at Week 36 (n=54, 67) -0.18  (0.05) -0.18  (0.04)
Change from Baseline at Week 52 (n=50, 56) -0.20  (0.04) -0.17  (0.04)
Change from Baseline at Week 52 LOCF (n=153, 161) -0.11  (0.04) -0.05  (0.04)
Highest Change from Baseline (n=153, 161) -0.02  (0.05) 0.15  (0.05)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.435
Comments Means, mean differences, 95% confidence intervals for the differences, and the p-values are based on ANOVA/ANCOVA model.
Method ANOVA
Comments ANOVA, controlling for treatment, used for baseline estimates.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-0.08 to 0.20
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from Baseline at Week 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariate=baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
0.04 to 0.30
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from Baseline at Week 24
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariate=baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.11 to 0.17
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from baseline at Week 36
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariate=baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.13 to 0.13
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from baseline at Week 52
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariate=baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.08 to 0.14
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Change from Baseline at Week 52 (LOCF)
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.358
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariate=baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
-0.06 to 0.17
Estimation Comments aripiprazole - placebo
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Phase 2 Double-Blind Treatment: Lamotrigine + Placebo, Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Comments Highest Change from Baseline
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.021
Comments Means, treatment differences between aripiprazole and placebo, 95% confidence intervals for the differences and the p-values for treatment comparisons are based on ANOVA/ANCOVA model.
Method ANCOVA
Comments ANCOVA (main effects=double-blind treatment, covariate=baseline assessment) used for mean change from baseline comparisons.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0.17
Confidence Interval (2-Sided) 95%
0.03 to 0.31
Estimation Comments aripiprazole - placebo
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Phase 1: Single-Blind Treatment, Lamotrigine + Aripiprazole Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Hide Arm/Group Description Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 1 (all subjects) - up to 24 weeks Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
All-Cause Mortality
Phase 1: Single-Blind Treatment, Lamotrigine + Aripiprazole Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Phase 1: Single-Blind Treatment, Lamotrigine + Aripiprazole Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   32/787 (4.07%)   9/165 (5.45%)   5/176 (2.84%) 
Blood and lymphatic system disorders       
ANAEMIA  1  0/787 (0.00%)  1/165 (0.61%)  0/176 (0.00%) 
Cardiac disorders       
CARDIAC DISORDER  1  0/787 (0.00%)  0/165 (0.00%)  1/176 (0.57%) 
VENTRICULAR FIBRILLATION  1  0/787 (0.00%)  1/165 (0.61%)  0/176 (0.00%) 
WOLFF-PARKINSON-WHITE SYNDROME  1  0/787 (0.00%)  1/165 (0.61%)  0/176 (0.00%) 
Gastrointestinal disorders       
INGUINAL HERNIA  1  0/787 (0.00%)  1/165 (0.61%)  0/176 (0.00%) 
GASTRITIS EROSIVE  1  1/787 (0.13%)  0/165 (0.00%)  0/176 (0.00%) 
MALLORY-WEISS SYNDROME  1  1/787 (0.13%)  0/165 (0.00%)  0/176 (0.00%) 
General disorders       
CHEST PAIN  1  3/787 (0.38%)  2/165 (1.21%)  0/176 (0.00%) 
NON-CARDIAC CHEST PAIN  1  1/787 (0.13%)  0/165 (0.00%)  0/176 (0.00%) 
Injury, poisoning and procedural complications       
HEAD INJURY  1  1/787 (0.13%)  0/165 (0.00%)  0/176 (0.00%) 
INTENTIONAL OVERDOSE  1  0/787 (0.00%)  1/165 (0.61%)  0/176 (0.00%) 
ROAD TRAFFIC ACCIDENT  1  1/787 (0.13%)  0/165 (0.00%)  0/176 (0.00%) 
Metabolism and nutrition disorders       
OBESITY  1  0/787 (0.00%)  0/165 (0.00%)  1/176 (0.57%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
VULVAL CANCER  1  1/787 (0.13%)  0/165 (0.00%)  0/176 (0.00%) 
UTERINE LEIOMYOMA  1  1/787 (0.13%)  0/165 (0.00%)  0/176 (0.00%) 
Nervous system disorders       
AKATHISIA  1  1/787 (0.13%)  0/165 (0.00%)  0/176 (0.00%) 
DIZZINESS  1  0/787 (0.00%)  1/165 (0.61%)  0/176 (0.00%) 
ALTERED STATE OF CONSCIOUSNESS  1  1/787 (0.13%)  0/165 (0.00%)  0/176 (0.00%) 
Pregnancy, puerperium and perinatal conditions       
PREGNANCY  1  0/787 (0.00%)  1/165 (0.61%)  0/176 (0.00%) 
Psychiatric disorders       
MANIA  1  3/787 (0.38%)  0/165 (0.00%)  0/176 (0.00%) 
ANXIETY  1  1/787 (0.13%)  0/165 (0.00%)  0/176 (0.00%) 
AGITATION  1  1/787 (0.13%)  0/165 (0.00%)  0/176 (0.00%) 
DEPRESSION  1  3/787 (0.38%)  0/165 (0.00%)  1/176 (0.57%) 
PANIC ATTACK  1  1/787 (0.13%)  0/165 (0.00%)  0/176 (0.00%) 
BIPOLAR DISORDER  1  2/787 (0.25%)  0/165 (0.00%)  0/176 (0.00%) 
COMPLETED SUICIDE  1  1/787 (0.13%)  0/165 (0.00%)  0/176 (0.00%) 
SUICIDAL IDEATION  1  8/787 (1.02%)  0/165 (0.00%)  0/176 (0.00%) 
BIPOLAR I DISORDER  1  2/787 (0.25%)  2/165 (1.21%)  1/176 (0.57%) 
DEPRESSIVE SYMPTOM  1  2/787 (0.25%)  0/165 (0.00%)  0/176 (0.00%) 
HOMICIDAL IDEATION  1  2/787 (0.25%)  0/165 (0.00%)  0/176 (0.00%) 
MENTAL STATUS CHANGES  1  0/787 (0.00%)  0/165 (0.00%)  1/176 (0.57%) 
Renal and urinary disorders       
NEPHROLITHIASIS  1  0/787 (0.00%)  1/165 (0.61%)  0/176 (0.00%) 
Reproductive system and breast disorders       
MENSTRUAL DISORDER  1  1/787 (0.13%)  0/165 (0.00%)  0/176 (0.00%) 
OVARIAN CYST RUPTURED  1  1/787 (0.13%)  0/165 (0.00%)  0/176 (0.00%) 
Social circumstances       
PHYSICAL ASSAULT  1  1/787 (0.13%)  0/165 (0.00%)  0/176 (0.00%) 
Vascular disorders       
HYPERTENSION  1  0/787 (0.00%)  1/165 (0.61%)  0/176 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase 1: Single-Blind Treatment, Lamotrigine + Aripiprazole Phase 2 Double-Blind Treatment: Lamotrigine + Placebo Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   545/787 (69.25%)   61/165 (36.97%)   74/176 (42.05%) 
Gastrointestinal disorders       
NAUSEA  1  103/787 (13.09%)  6/165 (3.64%)  7/176 (3.98%) 
VOMITING  1  40/787 (5.08%)  1/165 (0.61%)  1/176 (0.57%) 
DRY MOUTH  1  44/787 (5.59%)  3/165 (1.82%)  4/176 (2.27%) 
General disorders       
FATIGUE  1  74/787 (9.40%)  1/165 (0.61%)  5/176 (2.84%) 
Infections and infestations       
URINARY TRACT INFECTION  1  35/787 (4.45%)  9/165 (5.45%)  5/176 (2.84%) 
UPPER RESPIRATORY TRACT INFECTION  1  34/787 (4.32%)  13/165 (7.88%)  12/176 (6.82%) 
Musculoskeletal and connective tissue disorders       
BACK PAIN  1  26/787 (3.30%)  5/165 (3.03%)  9/176 (5.11%) 
Nervous system disorders       
HEADACHE  1  92/787 (11.69%)  13/165 (7.88%)  8/176 (4.55%) 
SEDATION  1  62/787 (7.88%)  3/165 (1.82%)  1/176 (0.57%) 
AKATHISIA  1  196/787 (24.90%)  10/165 (6.06%)  19/176 (10.80%) 
DIZZINESS  1  40/787 (5.08%)  3/165 (1.82%)  2/176 (1.14%) 
SOMNOLENCE  1  42/787 (5.34%)  0/165 (0.00%)  1/176 (0.57%) 
Psychiatric disorders       
ANXIETY  1  73/787 (9.28%)  6/165 (3.64%)  13/176 (7.39%) 
INSOMNIA  1  138/787 (17.53%)  19/165 (11.52%)  13/176 (7.39%) 
AGITATION  1  65/787 (8.26%)  8/165 (4.85%)  11/176 (6.25%) 
RESTLESSNESS  1  55/787 (6.99%)  2/165 (1.21%)  3/176 (1.70%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12
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.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
EMail: Clinical.Trials@bms.com
Layout table for additonal information
Responsible Party: Study Director, Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT00277212     History of Changes
Other Study ID Numbers: CN138-392 ST
First Submitted: January 13, 2006
First Posted: January 16, 2006
Results First Submitted: September 20, 2010
Results First Posted: October 20, 2010
Last Update Posted: December 2, 2013