Bipolar Disorder
Conditions
Keywords
Bipolar I Disorder with a recent manic or mixed episode
Brief summary
Efficacy of Aripiprazole in Combination with Lamotrigine in the Long-Term Maintenance Treatment of Bipolar I Disorder in Outpatients with Recent Manic or Mixed Episode
Interventions
DRUGLamotrigine + Aripiprazole
Tablets, Oral, once daily, Phase 1 (all subjects) - up to 24 weeks; Phase 2 - up to 52 weeks Lamotrigine 100-200 mg/day Aripiprazole 10-30 mg/day
DRUGLamotrigine + Placebo
Tablets, Oral, once daily, Phase 2 - up to 52 weeks Lamotrigine 100-200 mg/day placebo 0 mg/day
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Otsuka America Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women ≥ 18 years of age meeting Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (Text Revision) (DSM-IV-TR) criteria for bipolar I disorder, recently experiencing a manic or mixed episode with a history of one or more manic or mixed episodes of sufficient severity to require treatment with a mood stabilizer or antipsychotic
Exclusion criteria
* First manic episode * Current manic or mixed episode with \> 2 years duration * Treated with aripiprazole within the past 3 months * Allergic, intolerant, hypersensitive or refractory to aripiprazole or lamotrigine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | Proportion of Participants without Relapse Through Week 52 (Kaplan-Meier's estimated survival rate). |
| Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | Proportion of Participants without Relapse Through Week 52 (Kaplan-Meier's estimated survival rate). |
| Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 | Proportion of Participants without Discontinuation Through Week 52(Kaplan-Meier's estimated survival rate). |
| 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 | Throughout Phase 2 (up to 52 weeks) | 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. |
| Adjusted Mean Change From Baseline in Body Weight, Phase 2 | Baseline, Week 52 | Adjusted for index mood episode and baseline assessment |
| Number of Participants Showing Clinically Relevant Weight Loss by Study Week | Weeks 12, 24, 36, 52 | Weight Loss of at least a 7% decrease from Baseline. |
| Number of Participants Showing Clinically Relevant Weight Gain by Study Week | Weeks 12, 24, 36, 52 | Weight gain of at least a 7% increase from Baseline. |
| Adjusted Mean Change From Baseline in BMI by Study Week | Baseline, Weeks 12, 24, 36, 52 | Adjusted for index mood episode and baseline assessment. |
| Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Throughout the study, up to Week 52 | 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. |
| Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Up to 52 Weeks | 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. |
| Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Throughout Phase 2 of the study, up to Week 52 | 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) |
| Summary of Concomitant Medications, Phase 1 | Phase 1 (9 to 24 Week Single-blind Stabilization Phase) | — |
| Summary of Concomitant Medications, Phase 2 | Phase 2 (52 Week Double-blind Relapse Assessment Phase) | — |
| Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Baseline, Weeks 8, 24, 36, 52 | 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. |
| Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Baseline, Weeks 8, 24, 36, 52 | 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. |
| Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment, | Baseline, Weeks 8, 24, 36, 52 | 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. |
Countries
Puerto Rico, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1: Single-Blind Treatment, Lamotrigine + Aripiprazole Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 1 (all subjects) - up to 24 weeks | 796 |
| Total | 796 |
Baseline characteristics
| Characteristic | Phase 1: Single-Blind Treatment, Lamotrigine + Aripiprazole |
|---|---|
| Age, Continuous | 38.1 years STANDARD_DEVIATION 12 |
| BMI Category 18.5 <= BMI <25 | 221 participants |
| BMI Category 25 <= BMI <30 | 215 participants |
| BMI Category BMI <18.5 | 12 participants |
| BMI Category BMI >=30 | 321 participants |
| BMI Category Missing | 27 participants |
| Body Mass Index (BMI) | 29.7 kg/m^2 STANDARD_DEVIATION 7.6 |
| Race/Ethnicity, Customized Hispanic or Latino | 93 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 703 participants |
| RaceEthnicityOther American Indian/Alaska Native | 2 participants |
| RaceEthnicityOther Asian | 10 participants |
| RaceEthnicityOther Black/African American | 88 participants |
| RaceEthnicityOther Native Hawaiian/Other Pacific Islander | 1 participants |
| RaceEthnicityOther Other | 2 participants |
| RaceEthnicityOther White | 693 participants |
| Sex/Gender, Customized Female | 505 Participants |
| Sex/Gender, Customized Male | 291 Participants |
| Weight | 84.7 kg STANDARD_DEVIATION 22.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| other Total, other adverse events | 545 / 787 | 61 / 165 | 74 / 176 |
| serious Total, serious adverse events | 32 / 787 | 9 / 165 | 5 / 176 |
Outcome results
Primary
Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2)
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
Population: Randomized Participants (comprises all patients who are randomized in Phase 2). n= number of randomized participants evaluated at given time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 0 (n=173, n=178) | 1.00 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 2 (n=162, n=172) | 0.98 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 4 (n=154, n=159) | 0.97 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 6 (n=142, n=147) | 0.95 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 8 (n=135, n=135) | 0.93 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 12 (n=121, n=127) | 0.89 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 16 (n=101, n=127) | 0.88 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 20 (n=94, n=127) | 0.88 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 24 (n=86, n=127) | 0.84 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 28 (n=79, n=127) | 0.81 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 32 (n=69, n=83) | 0.78 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 36 (n=67, n=83) | 0.78 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 40 (n=62, n=83) | 0.77 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 44 (n=62, n=83) | 0.77 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 48 (n=62, n=83) | 0.77 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 52 (n=62, n=83) | 0.77 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 52 (n=62, n=83) | 0.89 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 0 (n=173, n=178) | 1.00 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 24 (n=86, n=127) | 0.90 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 2 (n=162, n=172) | 0.98 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 40 (n=62, n=83) | 0.89 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 4 (n=154, n=159) | 0.96 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 28 (n=79, n=127) | 0.90 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 6 (n=142, n=147) | 0.93 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 48 (n=62, n=83) | 0.89 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 8 (n=135, n=135) | 0.90 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 32 (n=69, n=83) | 0.89 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 12 (n=121, n=127) | 0.90 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 44 (n=62, n=83) | 0.89 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 16 (n=101, n=127) | 0.90 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 36 (n=67, n=83) | 0.89 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse Through Week 52 in the Double-Blind Relapse Assessment Phase (Phase 2) | Week 20 (n=94, n=127) | 0.90 Proportion of Participants |
p-value: 0.05895% CI: [0.296, 1.03]Log Rank
Secondary
Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Change from Baseline at Week 24 (n=85, 89) | -0.01 units on a scale | Standard Error 0.06 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Change from Baseline at Week 52 (n=50, 56) | -0.11 units on a scale | Standard Error 0.04 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Change from Baseline at Week 8 (n=124, 124) | -0.05 units on a scale | Standard Error 0.05 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Change from Baseline at Week 52 LOCF (n=153, 161) | 0.05 units on a scale | Standard Error 0.06 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Change from Baseline at Week 36 (n=54, 67) | -0.09 units on a scale | Standard Error 0.08 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Highest Change from Baseline (n=153, 161) | 0.10 units on a scale | Standard Error 0.07 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Baseline (n=125, 128) | 0.21 units on a scale | Standard Error 0.07 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Highest Change from Baseline (n=153, 161) | 0.14 units on a scale | Standard Error 0.07 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Baseline (n=125, 128) | 0.14 units on a scale | Standard Error 0.07 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Change from Baseline at Week 8 (n=124, 124) | 0.06 units on a scale | Standard Error 0.06 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Change from Baseline at Week 24 (n=85, 89) | 0.04 units on a scale | Standard Error 0.05 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Change from Baseline at Week 36 (n=54, 67) | 0.13 units on a scale | Standard Error 0.07 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Change from Baseline at Week 52 (n=50, 56) | -0.05 units on a scale | Standard Error 0.04 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Abnormal Involuntary Movement Scale (AIMS) Total Score | Change from Baseline at Week 52 LOCF (n=153, 161) | -0.01 units on a scale | Standard Error 0.06 |
Comparison: Baselinep-value: 0.45895% CI: [-0.25, 0.11]ANOVA
Comparison: Change from Baseline at Week 895% CI: [-0.05, 0.26]ANCOVA
Comparison: Change from baseline at Week 2495% CI: [-0.11, 0.2]ANCOVA
Comparison: Change from Baseline at Week 3695% CI: [0, 0.42]ANCOVA
Comparison: Change from Baseline at week 5295% CI: [-0.05, 0.16]ANCOVA
Comparison: Change from baseline at Week 52 (LOCF)p-value: 0.51595% CI: [-0.22, 0.11]ANCOVA
Comparison: Highest Change from Baselinep-value: 0.7395% CI: [-0.16, 0.23]ANCOVA
Secondary
Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment,
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment, | Change from Baseline at Week 8 (n=125, 124) | -0.12 units on a scale | Standard Error 0.05 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment, | Change from Baseline at Week 52 (n=50, 56) | -0.20 units on a scale | Standard Error 0.04 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment, | Baseline (n=125, 128) | 0.22 units on a scale | Standard Error 0.05 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment, | Change from Baseline at Week 52 LOCF (n=153, 161) | -0.11 units on a scale | Standard Error 0.04 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment, | Change from Baseline at Week 24 (n=85, 89) | -0.09 units on a scale | Standard Error 0.05 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment, | Highest Change from Baseline (n=153, 161) | -0.02 units on a scale | Standard Error 0.05 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment, | Change from Baseline at Week 36 (n=54, 67) | -0.18 units on a scale | Standard Error 0.05 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment, | Highest Change from Baseline (n=153, 161) | 0.15 units on a scale | Standard Error 0.05 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment, | Baseline (n=125, 128) | 0.27 units on a scale | Standard Error 0.05 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment, | Change from Baseline at Week 8 (n=125, 124) | 0.04 units on a scale | Standard Error 0.05 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment, | Change from Baseline at Week 36 (n=54, 67) | -0.18 units on a scale | Standard Error 0.04 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment, | Change from Baseline at Week 52 (n=50, 56) | -0.17 units on a scale | Standard Error 0.04 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment, | Change from Baseline at Week 52 LOCF (n=153, 161) | -0.05 units on a scale | Standard Error 0.04 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Barnes Akathisia Global Clinical Assessment, | Change from Baseline at Week 24 (n=85, 89) | -0.06 units on a scale | Standard Error 0.05 |
Comparison: Baselinep-value: 0.43595% CI: [-0.08, 0.2]ANOVA
Comparison: Change from Baseline at Week 895% CI: [0.04, 0.3]ANCOVA
Comparison: Change from Baseline at Week 2495% CI: [-0.11, 0.17]ANCOVA
Comparison: Change from baseline at Week 3695% CI: [-0.13, 0.13]ANCOVA
Comparison: Change from baseline at Week 5295% CI: [-0.08, 0.14]ANCOVA
Comparison: Change from Baseline at Week 52 (LOCF)p-value: 0.35895% CI: [-0.06, 0.17]ANCOVA
Comparison: Highest Change from Baselinep-value: 0.02195% CI: [0.03, 0.31]ANCOVA
Secondary
Adjusted Mean Change From Baseline in BMI by Study Week
Adjusted for index mood episode and baseline assessment.
Time frame: Baseline, Weeks 12, 24, 36, 52
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in BMI by Study Week | Change from Baseline Week 52 LOCF (n=143, 150) | -0.62 kg/m2 | Standard Error 0.17 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in BMI by Study Week | Highest Change from Baseline (n=143, 150) | -0.02 kg/m2 | Standard Error 0.15 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in BMI by Study Week | Baseline (n=143, 150) | 30.77 kg/m2 | Standard Error 0.63 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in BMI by Study Week | Change from Baseline Week 12 (n=105, 107) | -0.39 kg/m2 | Standard Error 0.15 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in BMI by Study Week | Change from Baseline Week 24 (n=84, 87) | -0.60 kg/m2 | Standard Error 0.2 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in BMI by Study Week | Change from Baseline Week 36 (n=54, 67) | -0.63 kg/m2 | Standard Error 0.33 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in BMI by Study Week | Change from Baseline Week 52 (n=49, 56) | -0.73 kg/m2 | Standard Error 0.37 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in BMI by Study Week | Change from Baseline Week 52 LOCF (n=143, 150) | 0.17 kg/m2 | Standard Error 0.17 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in BMI by Study Week | Change from Baseline Week 24 (n=84, 87) | 0.14 kg/m2 | Standard Error 0.2 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in BMI by Study Week | Highest Change from Baseline (n=143, 150) | 0.61 kg/m2 | Standard Error 0.14 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in BMI by Study Week | Change from Baseline Week 52 (n=49, 56) | 0.19 kg/m2 | Standard Error 0.34 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in BMI by Study Week | Baseline (n=143, 150) | 30.13 kg/m2 | Standard Error 0.61 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in BMI by Study Week | Change from Baseline Week 36 (n=54, 67) | 0.34 kg/m2 | Standard Error 0.3 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in BMI by Study Week | Change from Baseline Week 12 (n=105, 107) | -0.03 kg/m2 | Standard Error 0.15 |
Comparison: Baselinep-value: 0.46795% CI: [-2.37, 1.09]ANCOVA
Comparison: Change from Baseline at Week 1295% CI: [-0.06, 0.78]ANCOVA
Comparison: Change from baseline at Week 2495% CI: [0.19, 1.3]ANCOVA
Comparison: Change from baseline at Week 3695% CI: [0.08, 1.86]ANCOVA
Comparison: Change from baseline at Week 5295% CI: [-0.08, 1.92]ANCOVA
Comparison: Change from baseline at Week 52 (LOCF)p-value: 0.00195% CI: [0.31, 1.26]ANCOVA
Comparison: Highest Change from baselinep-value: 0.00295% CI: [0.23, 1.04]ANCOVA
Secondary
Adjusted Mean Change From Baseline in Body Weight, Phase 2
Adjusted for index mood episode and baseline assessment
Time frame: Baseline, Week 52
Population: Participants from the phase 2 Safety Sample who had body weight evaluation at baseline and week 52 LOCF.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Body Weight, Phase 2 | -1.81 kg | Standard Error 0.48 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Body Weight, Phase 2 | 0.43 kg | Standard Error 0.47 |
Comparison: Week 52 LOCFp-value: 0.00195% CI: [0.91, 3.57]ANCOVA
Secondary
Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score
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
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Change from Baseline at Week 24 (n=85, 89) | -0.21 units on a scale | Standard Error 0.13 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Change from Baseline at Week 52 (n=50, 56) | -0.35 units on a scale | Standard Error 0.13 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Change from Baseline at Week 8 (n=125, 124) | -0.20 units on a scale | Standard Error 0.1 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Change from Baseline at Week 52 LOCF (n=152, 161) | -0.22 units on a scale | Standard Error 0.1 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Change from Baseline at Week 36 (n=54, 67) | -0.38 units on a scale | Standard Error 0.11 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Highest Change from Baseline (n=152, 161) | 0.03 units on a scale | Standard Error 0.12 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Baseline (n=125, 128) | 10.59 units on a scale | Standard Error 0.12 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Highest Change from Baseline (n=152, 161) | 0.34 units on a scale | Standard Error 0.11 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Baseline (n=125, 128) | 10.58 units on a scale | Standard Error 0.12 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Change from Baseline at Week 8 (n=125, 124) | 0.05 units on a scale | Standard Error 0.1 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Change from Baseline at Week 24 (n=85, 89) | 0.03 units on a scale | Standard Error 0.13 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Change from Baseline at Week 36 (n=54, 67) | -0.14 units on a scale | Standard Error 0.1 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Change from Baseline at Week 52 (n=50, 56) | -0.05 units on a scale | Standard Error 0.12 |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Adjusted Mean Change From Baseline in Simpson-Angus Scale (SAS) Total Score | Change from Baseline at Week 52 LOCF (n=152, 161) | 0.02 units on a scale | Standard Error 0.1 |
Comparison: Baselinep-value: 0.97195% CI: [-0.35, 0.34]ANOVA
Comparison: Change from baseline at Week 895% CI: [-0.03, 0.51]ANCOVA
Comparison: Change from baseline at Week 2495% CI: [-0.13, 0.6]ANCOVA
Comparison: Change from Baseline at Week 3695% CI: [-0.06, 0.55]ANCOVA
Comparison: Change from baseline at Week 5295% CI: [-0.06, 0.65]ANCOVA
Comparison: Change from Baseline at Week 52 (LOCF)p-value: 0.09595% CI: [-0.04, 0.52]ANCOVA
Comparison: Highest change from Baselinep-value: 0.06195% CI: [-0.01, 0.63]ANCOVA
Secondary
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
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)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | 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 | Deaths | 0 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | 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 | Treatment-Emergent SAEs | 9 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | 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 | Suicide-Related SAEs | 0 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | 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 | AEs Leading to Discontinuation of Study Medication | 12 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | 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 | Treatment-Emergent AEs | 111 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | 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 | Treatment-Emergent EPS-Related AEs | 15 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | 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 | Treatment-Emergent AEs | 124 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | 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 | Deaths | 0 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | 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 | AEs Leading to Discontinuation of Study Medication | 14 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | 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 | Treatment-Emergent SAEs | 5 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | 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 | Treatment-Emergent EPS-Related AEs | 28 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | 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 | Suicide-Related SAEs | 0 participants |
Secondary
Number of Participants Showing Clinically Relevant Weight Gain by Study Week
Weight gain of at least a 7% increase from Baseline.
Time frame: Weeks 12, 24, 36, 52
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants Showing Clinically Relevant Weight Gain by Study Week | Week 12 (n=105, 107) | 2 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants Showing Clinically Relevant Weight Gain by Study Week | Week 24 (n=84, 87) | 3 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants Showing Clinically Relevant Weight Gain by Study Week | Week 36 (n=54, 67) | 5 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants Showing Clinically Relevant Weight Gain by Study Week | Week 52 (n=49, 56) | 2 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants Showing Clinically Relevant Weight Gain by Study Week | Week 52 LOCF (n=143, 151) | 5 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants Showing Clinically Relevant Weight Gain by Study Week | At Any Time (n=147, 154) | 8 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants Showing Clinically Relevant Weight Gain by Study Week | Week 52 LOCF (n=143, 151) | 18 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants Showing Clinically Relevant Weight Gain by Study Week | Week 12 (n=105, 107) | 4 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants Showing Clinically Relevant Weight Gain by Study Week | Week 52 (n=49, 56) | 7 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants Showing Clinically Relevant Weight Gain by Study Week | Week 24 (n=84, 87) | 10 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants Showing Clinically Relevant Weight Gain by Study Week | At Any Time (n=147, 154) | 27 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants Showing Clinically Relevant Weight Gain by Study Week | Week 36 (n=54, 67) | 14 Participants |
Comparison: Week 52 LOCFp-value: 0.00795% CI: [1.3, 8.94]Cochran-Mantel-Haenszel
p-value: 0.001Cochran-Mantel-Haenszel
Secondary
Number of Participants Showing Clinically Relevant Weight Loss by Study Week
Weight Loss of at least a 7% decrease from Baseline.
Time frame: Weeks 12, 24, 36, 52
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants Showing Clinically Relevant Weight Loss by Study Week | Week 12 (n=105, 107) | 7 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants Showing Clinically Relevant Weight Loss by Study Week | Week 24 (n=84, 87) | 8 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants Showing Clinically Relevant Weight Loss by Study Week | Week 36 (n=54, 67) | 10 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants Showing Clinically Relevant Weight Loss by Study Week | Week 52 (n=49, 56) | 10 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants Showing Clinically Relevant Weight Loss by Study Week | Week 52 LOCF (n=143, 151) | 22 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants Showing Clinically Relevant Weight Loss by Study Week | At Any Time (n=147, 154) | 26 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants Showing Clinically Relevant Weight Loss by Study Week | Week 52 LOCF (n=143, 151) | 13 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants Showing Clinically Relevant Weight Loss by Study Week | Week 12 (n=105, 107) | 9 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants Showing Clinically Relevant Weight Loss by Study Week | Week 52 (n=49, 56) | 6 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants Showing Clinically Relevant Weight Loss by Study Week | Week 24 (n=84, 87) | 9 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants Showing Clinically Relevant Weight Loss by Study Week | At Any Time (n=147, 154) | 19 Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants Showing Clinically Relevant Weight Loss by Study Week | Week 36 (n=54, 67) | 6 Participants |
Comparison: Week 52 LOCFp-value: 0.07395% CI: [0.29, 1.07]Cochran-Mantel-Haenszel
Comparison: At Any Timep-value: 0.194Cochran-Mantel-Haenszel
Secondary
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
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
Population: Phase 2 safety sample
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Prolactin (n=152, 158) | 32 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | LDL-C (fasting) (n=126, 124) | 14 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Creatine kinase (n=3, 1) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | LDL-C (non-fasting) (n=68, 75) | 7 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Cholesterol Total (n=151, 157) | 22 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Triglycerides (n=151, 157) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | LDH ≥3 x ULN (n=151, 158) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Triglycerides (fasting) (n=126, 124) | 26 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Cholesterol Total (fasting) (n=126, 124) | 17 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Triglycerides (non-fasting) (n=68, 75) | 19 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Creatinine ≥2.0 mg/dL (n=151, 157) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Sodium serum (n=152, 158) | 1 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Cholesterol Total (non-fasting) (n=68, 75) | 9 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Potassium serum (n=152, 158) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | ALP ≥3 x ULN (n=151, 157) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Chloride serum (n=152, 158) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Glucose Fasting Serum (n=126, 125) | 15 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Calcium (n=151, 157) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Uric acid (n=151, 157) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Hemoglobin ≤11.5 g/dL(m)/≤9.5 g/dL(f) (n=152, 156) | 1 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | HDL-C (n=151, 158) | 53 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Hematocrit ≤37(m)/≤32(f) & 3 ↓from BL (n=152,156) | 1 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | BUN ≥30 mg/dL (n=151, 158) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Leukocytes ≤2800 mm^3 or ≥16000 mm^3 (n=152, 156) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | HDL-C (fasting) (n=126, 125) | 44 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Eosinophils relative (calculated)≥10% (n=152, 156) | 2 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Bilirubin (total) ≥ 2.0 mg/dL (n=152, 157) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Neutrophils relative (calculated)≤15% (n=152, 156) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | HDL-C (non-fasting) (n=68, 75) | 23 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Platelets ≤75,000 mm3 or ≥700,000 mm3 (n=152,155) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | AST ≥3 x ULN (n=151, 157) | 2 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Protein urine increase of ≥2 units (n=145, 152) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | LDL-C (n=151, 157) | 17 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Glucose urine (n=149, 155) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | ALT ≥3 x ULN (n=151,157) | 3 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Glucose urine (n=149, 155) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | ALT ≥3 x ULN (n=151,157) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | AST ≥3 x ULN (n=151, 157) | 1 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | ALP ≥3 x ULN (n=151, 157) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | LDH ≥3 x ULN (n=151, 158) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | BUN ≥30 mg/dL (n=151, 158) | 2 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Creatine kinase (n=3, 1) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Creatinine ≥2.0 mg/dL (n=151, 157) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Uric acid (n=151, 157) | 2 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Bilirubin (total) ≥ 2.0 mg/dL (n=152, 157) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Prolactin (n=152, 158) | 18 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Cholesterol Total (n=151, 157) | 28 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Cholesterol Total (fasting) (n=126, 124) | 25 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Cholesterol Total (non-fasting) (n=68, 75) | 7 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Glucose Fasting Serum (n=126, 125) | 13 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | HDL-C (n=151, 158) | 38 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | HDL-C (fasting) (n=126, 125) | 25 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | HDL-C (non-fasting) (n=68, 75) | 19 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | LDL-C (n=151, 157) | 26 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | LDL-C (fasting) (n=126, 124) | 22 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | LDL-C (non-fasting) (n=68, 75) | 5 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Triglycerides (n=151, 157) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Triglycerides (fasting) (n=126, 124) | 29 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Triglycerides (non-fasting) (n=68, 75) | 20 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Sodium serum (n=152, 158) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Potassium serum (n=152, 158) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Chloride serum (n=152, 158) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Calcium (n=151, 157) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Hemoglobin ≤11.5 g/dL(m)/≤9.5 g/dL(f) (n=152, 156) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Hematocrit ≤37(m)/≤32(f) & 3 ↓from BL (n=152,156) | 3 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Leukocytes ≤2800 mm^3 or ≥16000 mm^3 (n=152, 156) | 2 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Eosinophils relative (calculated)≥10% (n=152, 156) | 2 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Neutrophils relative (calculated)≤15% (n=152, 156) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Platelets ≤75,000 mm3 or ≥700,000 mm3 (n=152,155) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2) | Protein urine increase of ≥2 units (n=145, 152) | 0 particiapnts |
Secondary
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Systolic BP, supine-Decrease (n=160,168) | 7 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Diastolic BP, standing-Increase (n=153,157) | 6 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Systolic BP, standing-Decrease (n=153,157) | 2 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Diastolic BP, standing-Decrease (n=153,157) | 0 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Systolic BP, supine-Increase (n=160,168) | 3 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Heart Rate, supine-Increase (n=160,168) | 0 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Heart Rate, supine-Decrease (n=160,168) | 3 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Diastolic BP, supine-Increase (n=160,168) | 2 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Heart Rate, standing-Increase (n=153, 157) | 4 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Systolic BP, standing-Increase (n=153, 157) | 3 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Heart Rate, standing-Decrease (n=153, 157) | 1 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Diastolic BP, supine-Decrease (n=160,168) | 0 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Heart Rate, standing-Decrease (n=153, 157) | 0 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Systolic BP, supine-Increase (n=160,168) | 1 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Systolic BP, supine-Decrease (n=160,168) | 5 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Systolic BP, standing-Increase (n=153, 157) | 0 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Systolic BP, standing-Decrease (n=153,157) | 4 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Diastolic BP, supine-Increase (n=160,168) | 0 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Diastolic BP, supine-Decrease (n=160,168) | 3 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Diastolic BP, standing-Increase (n=153,157) | 1 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Diastolic BP, standing-Decrease (n=153,157) | 1 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Heart Rate, supine-Decrease (n=160,168) | 0 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Heart Rate, standing-Increase (n=153, 157) | 2 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment | Heart Rate, supine-Increase (n=160,168) | 0 participants |
Secondary
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Supraventricular Tachycardia: not present→ present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Bradycardia: ≤ 50 bpm and ↓ 15 bpm | 2 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Sinus Tachycardia: ≥ 120 bpm and ↑ ≥ 15 bpm | 1 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Sinus Bradycardia: ≤ 50 bpm and ↓ 15 bpm | 2 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | SPB: not present → present (see description) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | VPB: not present → present (see description) | 2 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Tachycardia: ≥ 120 bpm and ↑ ≥ 15 bpm | 1 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Ventricular Tachycardia: not present → present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Atrial Fibrillation (AF): not present → present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | AF With Rapid Ventricular Response | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Atrial Flutter: not present → present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | 1st Degree A-V Block: PR ≥0.20 sec and ↑ ≥0.05 sec | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | 2nd Degree A-V Block: not present → present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | 3rd Degree A-V Block: not present → present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Left Bundle Branch Block: not present → present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Right Bundle Branch Block: not present → present | 6 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Pre-excitation Syndrome: not present → present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Other Intraventricular Conduction: see description | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Acute Infarction: not present → present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Subacute (recent) Infarction: not present→ present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Old Infarction: not present → present | 1 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Myocardial Ischemia: not present → present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Symmetrical T-Wave Inversions: not present→present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | QTc Bazett: > 450 msec | 5 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | QTc (.37): > 450 msec | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | QTc (.33): > 450 msec | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Subacute (recent) Infarction: not present→ present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Tachycardia: ≥ 120 bpm and ↑ ≥ 15 bpm | 1 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | 3rd Degree A-V Block: not present → present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Bradycardia: ≤ 50 bpm and ↓ 15 bpm | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | QTc (.37): > 450 msec | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Sinus Tachycardia: ≥ 120 bpm and ↑ ≥ 15 bpm | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Left Bundle Branch Block: not present → present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Sinus Bradycardia: ≤ 50 bpm and ↓ 15 bpm | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Old Infarction: not present → present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | SPB: not present → present (see description) | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Right Bundle Branch Block: not present → present | 4 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | VPB: not present → present (see description) | 1 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | QTc Bazett: > 450 msec | 6 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Supraventricular Tachycardia: not present→ present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Pre-excitation Syndrome: not present → present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Ventricular Tachycardia: not present → present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Myocardial Ischemia: not present → present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Atrial Fibrillation (AF): not present → present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Other Intraventricular Conduction: see description | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | AF With Rapid Ventricular Response | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | QTc (.33): > 450 msec | 1 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Atrial Flutter: not present → present | 1 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Acute Infarction: not present → present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | 1st Degree A-V Block: PR ≥0.20 sec and ↑ ≥0.05 sec | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | Symmetrical T-Wave Inversions: not present→present | 0 particiapnts |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment | 2nd Degree A-V Block: not present → present | 0 particiapnts |
Secondary
Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2)
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
Population: Randomized Participants (comprises all patients who are randomized in Phase 2). n= number of randomized participants evaluated at given time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 0 (n=173, n=178) | 1.00 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 2 (n=163, n=175) | 0.98 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 4 (n=151, n=160) | 0.94 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 6 (n=145, n=149) | 0.91 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 8 (n=132, n=136) | 0.89 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 12 (n=119, n=123) | 0.85 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 16 (n=102, n=113) | 0.84 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 20 (n=102, n=111) | 0.84 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 24 (n=91, n=95) | 0.82 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 28 (n=79, n=85) | 0.79 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 32 (n=74, n=82) | 0.79 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 36 (n=74, n=76) | 0.79 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 40 (n=74, n=70) | 0.79 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 44 (n=74, n=70) | 0.79 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 48 (n=74, n=70) | 0.79 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 52 (n=19, n=70) | 0.76 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 52 (n=19, n=70) | 0.82 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 0 (n=173, n=178) | 1.00 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 24 (n=91, n=95) | 0.87 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 2 (n=163, n=175) | 0.98 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 40 (n=74, n=70) | 0.82 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 4 (n=151, n=160) | 0.95 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 28 (n=79, n=85) | 0.85 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 6 (n=145, n=149) | 0.94 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 48 (n=74, n=70) | 0.82 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 8 (n=132, n=136) | 0.93 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 32 (n=74, n=82) | 0.84 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 12 (n=119, n=123) | 0.90 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 44 (n=74, n=70) | 0.82 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 16 (n=102, n=113) | 0.89 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 36 (n=74, n=76) | 0.83 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing a Depressive Relapse in the Double-blind Relapse Assessment Phase (Phase 2) | Week 20 (n=102, n=111) | 0.89 Proportion of Participants |
p-value: 0.38195% CI: [0.454, 1.354]Log Rank
Secondary
Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2
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
Population: Randomized Participants (comprises all patients who are randomized in Phase 2). n= number of randomized participants evaluated at given time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 0 (n=173, n=178) | 1.00 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 2 (n=163, n=175) | 0.96 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 4 (n=154, n=160) | 0.91 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 6 (n=145, n=149) | 0.87 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 8 (n=135, n=136) | 0.83 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 12 (n=121, n=123) | 0.76 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 16 (n=102, n=113) | 0.75 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 20 (n=94, n=111) | 0.74 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 24 (n=91, n=95) | 0.69 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 28 (n=78, n=85) | 0.65 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 32 (n=69, n=83) | 0.62 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 36 (n=67, n=76) | 0.62 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 40 (n=62, n=70) | 0.61 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 44 (n=62, n=70) | 0.61 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 48 (n=62, n=70) | 0.61 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 52 (n=19, n=70) | 0.58 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 52 (n=19, n=70) | 0.73 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 0 (n=173, n=178) | 1.00 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 24 (n=91, n=95) | 0.78 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 2 (n=163, n=175) | 0.95 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 40 (n=62, n=70) | 0.73 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 4 (n=154, n=160) | 0.91 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 28 (n=78, n=85) | 0.77 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 6 (n=145, n=149) | 0.88 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 48 (n=62, n=70) | 0.73 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 8 (n=135, n=136) | 0.84 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 32 (n=69, n=83) | 0.75 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 12 (n=121, n=123) | 0.82 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 44 (n=62, n=70) | 0.73 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 16 (n=102, n=113) | 0.80 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 36 (n=67, n=76) | 0.74 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Not Experiencing Relapse (Manic, Mixed, Depressive) in the Double-blind Relapse Assessment Phase Phase 2 | Week 20 (n=94, n=111) | 0.80 Proportion of Participants |
p-value: 0.05595% CI: [0.446, 1.011]Log Rank
Secondary
Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2)
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
Population: Randomized Participants (comprises all patients who are randomized in Phase 2). n= number of randomized participants evaluated at given time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 0 (n=173, n=178) | 0.95 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 2 (n=164, n=175) | 0.90 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 4 (n=155, n=161) | 0.84 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 6 (n=145, n=149) | 0.79 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 8 (n=135, n=138) | 0.71 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 12 (n=122, n=124) | 0.61 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 16 (n=103, n=115) | 0.55 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 20 (n=95, n=110) | 0.53 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 24 (n=90, n=104) | 0.46 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 28 (n=78, n=89) | 0.41 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 32 (n=70, n=83) | 0.38 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 36 (n=64, n=77) | 0.36 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 40 (n=61, n=72) | 0.34 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 44 (n=57, n=69) | 0.33 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 48 (n=56, n=66) | 0.32 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 52 (n=19, n=65) | 0.25 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 52 (n=19, n=65) | 0.37 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 0 (n=173, n=178) | 0.99 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 24 (n=90, n=104) | 0.51 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 2 (n=164, n=175) | 0.91 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 40 (n=61, n=72) | 0.39 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 4 (n=155, n=161) | 0.84 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 28 (n=78, n=89) | 0.47 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 6 (n=145, n=149) | 0.78 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 48 (n=56, n=66) | 0.37 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 8 (n=135, n=138) | 0.70 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 32 (n=70, n=83) | 0.44 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 12 (n=122, n=124) | 0.65 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 44 (n=57, n=69) | 0.38 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 16 (n=103, n=115) | 0.62 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 36 (n=64, n=77) | 0.41 Proportion of Participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Proportion of Participants Without Discontinuation for Any Reason in the Double-blind Relapse Assessment Phase (Phase 2) | Week 20 (n=95, n=110) | 0.59 Proportion of Participants |
p-value: 0.29595% CI: [0.672, 1.128]Log Rank
Secondary
Summary of Concomitant Medications, Phase 1
Time frame: Phase 1 (9 to 24 Week Single-blind Stabilization Phase)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 1 | Any central nervous system Medication | 550 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 1 | Analgesic | 2 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 1 | Anesthetic, general | 1 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 1 | Anesthetic, local | 3 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 1 | Anticholinergic | 98 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 1 | Antidepressant | 12 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 1 | Antiepileptic | 48 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 1 | Antimigraine prep | 12 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 1 | Antipsychotic | 20 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 1 | Anxiolytic | 267 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 1 | Hypnotic & Sedative | 206 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 1 | Opiod | 78 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 1 | Other Analgesic & Antipyretic | 253 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 1 | Other Nervous System Drug | 1 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 1 | Psychostimulant | 2 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 1 | Any extrapyramidal syndrome Medication | 98 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 1 | Benztropine | 98 participants |
Secondary
Summary of Concomitant Medications, Phase 2
Time frame: Phase 2 (52 Week Double-blind Relapse Assessment Phase)
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 2 | Antiepileptic | 8 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 2 | Hypnotic & Sedative | 50 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 2 | Anesthetic, local | 1 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 2 | Opiod | 20 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 2 | Antimigraine prep | 1 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 2 | Other Analgesic & Antipyretic | 53 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 2 | Antidepressant | 3 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 2 | Psychostimulant | 0 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 2 | Antipsychotic | 5 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 2 | Any extrapyramidal syndrome Medication | 25 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 2 | Any central nervous system Medication | 120 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 2 | Benztropine | 25 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 2 | Anxiolytic | 63 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 2 | Trihexyphenidyl | 1 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Placebo | Summary of Concomitant Medications, Phase 2 | Anticholinergic | 21 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Summary of Concomitant Medications, Phase 2 | Trihexyphenidyl | 1 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Summary of Concomitant Medications, Phase 2 | Any central nervous system Medication | 132 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Summary of Concomitant Medications, Phase 2 | Anesthetic, local | 0 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Summary of Concomitant Medications, Phase 2 | Anticholinergic | 25 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Summary of Concomitant Medications, Phase 2 | Antidepressant | 1 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Summary of Concomitant Medications, Phase 2 | Antiepileptic | 11 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Summary of Concomitant Medications, Phase 2 | Antimigraine prep | 3 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Summary of Concomitant Medications, Phase 2 | Antipsychotic | 3 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Summary of Concomitant Medications, Phase 2 | Anxiolytic | 62 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Summary of Concomitant Medications, Phase 2 | Hypnotic & Sedative | 41 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Summary of Concomitant Medications, Phase 2 | Opiod | 14 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Summary of Concomitant Medications, Phase 2 | Other Analgesic & Antipyretic | 66 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Summary of Concomitant Medications, Phase 2 | Psychostimulant | 1 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Summary of Concomitant Medications, Phase 2 | Any extrapyramidal syndrome Medication | 35 participants |
| Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole | Summary of Concomitant Medications, Phase 2 | Benztropine | 35 participants |