Trial Outcomes & Findings for A Phase IV Study of the Safety and Efficacy of Aripiprazole in Combination With Lamotrigine in the Long-Term Maintenance Treatment of Patients With Bipolar I Disorder With A Recent Manic or Mixed Episode (NCT NCT00277212)
NCT ID: NCT00277212
Last Updated: 2013-12-02
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
1169 participants
Primary outcome timeframe
Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52
Results posted on
2013-12-02
Participant Flow
A total of 1169 patients were enrolled in the study; 382 participants were considered baseline failures and did not enter Phase 1.
Participant milestones
| Measure |
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
|
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|---|
|
Phase 1 - Single-Blind Treatment
STARTED
|
787
|
0
|
0
|
|
Phase 1 - Single-Blind Treatment
Phase 1 Safety Sample
|
787
|
0
|
0
|
|
Phase 1 - Single-Blind Treatment
Phase 1 Efficacy Sample
|
756
|
0
|
0
|
|
Phase 1 - Single-Blind Treatment
COMPLETED
|
352
|
0
|
0
|
|
Phase 1 - Single-Blind Treatment
NOT COMPLETED
|
435
|
0
|
0
|
|
Phase 2 - Double-Blind Treatment
STARTED
|
0
|
173
|
178
|
|
Phase 2 - Double-Blind Treatment
Phase 2 Safety Sample
|
0
|
165
|
176
|
|
Phase 2 - Double-Blind Treatment
Phase 2 Efficacy Sample
|
0
|
164
|
174
|
|
Phase 2 - Double-Blind Treatment
COMPLETED
|
0
|
53
|
65
|
|
Phase 2 - Double-Blind Treatment
NOT COMPLETED
|
0
|
120
|
113
|
Reasons for withdrawal
| Measure |
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
|
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|---|
|
Phase 1 - Single-Blind Treatment
Lack of Efficacy
|
61
|
0
|
0
|
|
Phase 1 - Single-Blind Treatment
Adverse Event
|
93
|
0
|
0
|
|
Phase 1 - Single-Blind Treatment
Withdrawal by Subject
|
96
|
0
|
0
|
|
Phase 1 - Single-Blind Treatment
Lost to Follow-up
|
87
|
0
|
0
|
|
Phase 1 - Single-Blind Treatment
Poor/Noncompliance
|
35
|
0
|
0
|
|
Phase 1 - Single-Blind Treatment
Pregnancy
|
6
|
0
|
0
|
|
Phase 1 - Single-Blind Treatment
Subject No Longer Met Study Criteria
|
44
|
0
|
0
|
|
Phase 1 - Single-Blind Treatment
Administrative Reason by Sponsor
|
1
|
0
|
0
|
|
Phase 1 - Single-Blind Treatment
Other Reasons
|
12
|
0
|
0
|
|
Phase 2 - Double-Blind Treatment
Lack of Efficacy
|
0
|
54
|
39
|
|
Phase 2 - Double-Blind Treatment
Adverse Event
|
0
|
10
|
16
|
|
Phase 2 - Double-Blind Treatment
Withdrawal by Subject
|
0
|
17
|
16
|
|
Phase 2 - Double-Blind Treatment
Lost to Follow-up
|
0
|
18
|
18
|
|
Phase 2 - Double-Blind Treatment
Poor/Noncompliance
|
0
|
7
|
8
|
|
Phase 2 - Double-Blind Treatment
Pregnancy
|
0
|
2
|
2
|
|
Phase 2 - Double-Blind Treatment
Subject No Longer Meets Study Criteria
|
0
|
4
|
6
|
|
Phase 2 - Double-Blind Treatment
Administrative Reasons By Sponsor
|
0
|
1
|
3
|
|
Phase 2 - Double-Blind Treatment
Other reasons
|
0
|
7
|
5
|
Baseline Characteristics
A Phase IV Study of the Safety and Efficacy of Aripiprazole in Combination With Lamotrigine in the Long-Term Maintenance Treatment of Patients With Bipolar I Disorder With A Recent Manic or Mixed Episode
Baseline characteristics by cohort
| Measure |
Phase 1: Single-Blind Treatment, Lamotrigine + Aripiprazole
n=796 Participants
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 1 (all subjects) - up to 24 weeks
|
|---|---|
|
Age Continuous
|
38.1 years
STANDARD_DEVIATION 12.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
505 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
291 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
693 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Black/African American
|
88 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian
|
10 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian/Alaska Native
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian/Other Pacific Islander
|
1 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Other
|
2 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic or Latino
|
93 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Not Hispanic or Latino
|
703 participants
n=5 Participants
|
|
Body Mass Index (BMI)
|
29.7 kg/m^2
STANDARD_DEVIATION 7.6 • n=5 Participants
|
|
Weight
|
84.7 kg
STANDARD_DEVIATION 22.7 • n=5 Participants
|
|
BMI Category
18.5 <= BMI <25
|
221 participants
n=5 Participants
|
|
BMI Category
25 <= BMI <30
|
215 participants
n=5 Participants
|
|
BMI Category
BMI <18.5
|
12 participants
n=5 Participants
|
|
BMI Category
BMI >=30
|
321 participants
n=5 Participants
|
|
BMI Category
Missing
|
27 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52Population: Randomized Participants (comprises all patients who are randomized in Phase 2). n= number of randomized participants evaluated at given time point.
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).
Outcome measures
| Measure |
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
n=173 Participants
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
n=178 Participants
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|
|
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
|
0.89 Proportion of Participants
|
|
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
|
1.00 Proportion of Participants
|
|
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
|
0.98 Proportion of Participants
|
|
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
|
0.96 Proportion of Participants
|
|
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
|
0.93 Proportion of Participants
|
|
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
|
0.90 Proportion of Participants
|
|
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
|
0.90 Proportion of Participants
|
|
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
|
0.90 Proportion of Participants
|
|
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
|
0.90 Proportion of Participants
|
|
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
|
0.90 Proportion of Participants
|
|
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
|
0.90 Proportion of Participants
|
|
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
|
0.89 Proportion of Participants
|
|
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
|
0.89 Proportion of Participants
|
|
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
|
0.89 Proportion of Participants
|
|
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
|
0.89 Proportion of Participants
|
|
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
|
0.89 Proportion of Participants
|
SECONDARY outcome
Timeframe: Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52Population: Randomized Participants (comprises all patients who are randomized in Phase 2). n= number of randomized participants evaluated at given time point.
Proportion of Participants without Relapse Through Week 52 (Kaplan-Meier's estimated survival rate).
Outcome measures
| Measure |
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
n=173 Participants
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
n=178 Participants
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|
|
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
|
1.00 Proportion of Participants
|
|
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
|
0.95 Proportion of Participants
|
|
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
|
0.91 Proportion of Participants
|
|
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
|
0.88 Proportion of Participants
|
|
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
|
0.84 Proportion of Participants
|
|
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
|
0.82 Proportion of Participants
|
|
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
|
0.80 Proportion of Participants
|
|
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
|
0.80 Proportion of Participants
|
|
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
|
0.78 Proportion of Participants
|
|
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
|
0.77 Proportion of Participants
|
|
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
|
0.75 Proportion of Participants
|
|
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
|
0.74 Proportion of Participants
|
|
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
|
0.73 Proportion of Participants
|
|
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
|
0.73 Proportion of Participants
|
|
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
|
0.73 Proportion of Participants
|
|
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
|
0.73 Proportion of Participants
|
SECONDARY outcome
Timeframe: Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52Population: Randomized Participants (comprises all patients who are randomized in Phase 2). n= number of randomized participants evaluated at given time point.
Proportion of Participants without Relapse Through Week 52 (Kaplan-Meier's estimated survival rate).
Outcome measures
| Measure |
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
n=173 Participants
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
n=178 Participants
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|
|
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
|
1.00 Proportion of Participants
|
|
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
|
0.98 Proportion of Participants
|
|
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
|
0.95 Proportion of Participants
|
|
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
|
0.94 Proportion of Participants
|
|
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
|
0.93 Proportion of Participants
|
|
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
|
0.90 Proportion of Participants
|
|
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
|
0.89 Proportion of Participants
|
|
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
|
0.89 Proportion of Participants
|
|
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
|
0.87 Proportion of Participants
|
|
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
|
0.85 Proportion of Participants
|
|
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
|
0.84 Proportion of Participants
|
|
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
|
0.83 Proportion of Participants
|
|
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
|
0.82 Proportion of Participants
|
|
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
|
0.82 Proportion of Participants
|
|
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
|
0.82 Proportion of Participants
|
|
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
|
0.82 Proportion of Participants
|
SECONDARY outcome
Timeframe: Weeks 0, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52Population: Randomized Participants (comprises all patients who are randomized in Phase 2). n= number of randomized participants evaluated at given time point.
Proportion of Participants without Discontinuation Through Week 52(Kaplan-Meier's estimated survival rate).
Outcome measures
| Measure |
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
n=173 Participants
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
n=178 Participants
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|
|
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
|
0.41 Proportion of Participants
|
|
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
|
0.99 Proportion of Participants
|
|
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
|
0.91 Proportion of Participants
|
|
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
|
0.84 Proportion of Participants
|
|
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
|
0.78 Proportion of Participants
|
|
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
|
0.70 Proportion of Participants
|
|
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
|
0.65 Proportion of Participants
|
|
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
|
0.62 Proportion of Participants
|
|
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
|
0.59 Proportion of Participants
|
|
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
|
0.51 Proportion of Participants
|
|
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
|
0.47 Proportion of Participants
|
|
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
|
0.44 Proportion of Participants
|
|
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
|
0.39 Proportion of Participants
|
|
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
|
0.38 Proportion of Participants
|
|
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
|
0.37 Proportion of Participants
|
|
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
|
0.37 Proportion of Participants
|
SECONDARY outcome
Timeframe: 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.
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.
Outcome measures
| Measure |
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
n=165 Participants
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
n=176 Participants
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|
|
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
|
0 participants
|
|
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
|
5 participants
|
|
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
|
0 participants
|
|
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
|
14 participants
|
|
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
|
124 participants
|
|
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
|
28 participants
|
SECONDARY outcome
Timeframe: Baseline, Week 52Population: Participants from the phase 2 Safety Sample who had body weight evaluation at baseline and week 52 LOCF.
Adjusted for index mood episode and baseline assessment
Outcome measures
| Measure |
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
n=143 Participants
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
n=151 Participants
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|
|
Adjusted Mean Change From Baseline in Body Weight, Phase 2
|
-1.81 kg
Standard Error 0.48
|
0.43 kg
Standard Error 0.47
|
SECONDARY outcome
Timeframe: Weeks 12, 24, 36, 52Population: 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.
Weight Loss of at least a 7% decrease from Baseline.
Outcome measures
| Measure |
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
n=165 Participants
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
n=176 Participants
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|
|
Number of Participants Showing Clinically Relevant Weight Loss by Study Week
Week 12 (n=105, 107)
|
7 Participants
|
9 Participants
|
|
Number of Participants Showing Clinically Relevant Weight Loss by Study Week
Week 24 (n=84, 87)
|
8 Participants
|
9 Participants
|
|
Number of Participants Showing Clinically Relevant Weight Loss by Study Week
Week 36 (n=54, 67)
|
10 Participants
|
6 Participants
|
|
Number of Participants Showing Clinically Relevant Weight Loss by Study Week
Week 52 (n=49, 56)
|
10 Participants
|
6 Participants
|
|
Number of Participants Showing Clinically Relevant Weight Loss by Study Week
Week 52 LOCF (n=143, 151)
|
22 Participants
|
13 Participants
|
|
Number of Participants Showing Clinically Relevant Weight Loss by Study Week
At Any Time (n=147, 154)
|
26 Participants
|
19 Participants
|
SECONDARY outcome
Timeframe: Weeks 12, 24, 36, 52Population: 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.
Weight gain of at least a 7% increase from Baseline.
Outcome measures
| Measure |
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
n=165 Participants
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
n=176 Participants
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|
|
Number of Participants Showing Clinically Relevant Weight Gain by Study Week
Week 12 (n=105, 107)
|
2 Participants
|
4 Participants
|
|
Number of Participants Showing Clinically Relevant Weight Gain by Study Week
Week 24 (n=84, 87)
|
3 Participants
|
10 Participants
|
|
Number of Participants Showing Clinically Relevant Weight Gain by Study Week
Week 36 (n=54, 67)
|
5 Participants
|
14 Participants
|
|
Number of Participants Showing Clinically Relevant Weight Gain by Study Week
Week 52 (n=49, 56)
|
2 Participants
|
7 Participants
|
|
Number of Participants Showing Clinically Relevant Weight Gain by Study Week
Week 52 LOCF (n=143, 151)
|
5 Participants
|
18 Participants
|
|
Number of Participants Showing Clinically Relevant Weight Gain by Study Week
At Any Time (n=147, 154)
|
8 Participants
|
27 Participants
|
SECONDARY outcome
Timeframe: Baseline, Weeks 12, 24, 36, 52Population: 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.
Adjusted for index mood episode and baseline assessment.
Outcome measures
| Measure |
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
n=165 Participants
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
n=176 Participants
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|
|
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
|
0.19 kg/m2
Standard Error 0.34
|
|
Adjusted Mean Change From Baseline in BMI by Study Week
Baseline (n=143, 150)
|
30.77 kg/m2
Standard Error 0.63
|
30.13 kg/m2
Standard Error 0.61
|
|
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
|
-0.03 kg/m2
Standard Error 0.15
|
|
Adjusted Mean Change From Baseline in BMI by Study Week
Change from Baseline Week 24 (n=84, 87)
|
-0.60 kg/m2
Standard Error 0.20
|
0.14 kg/m2
Standard Error 0.20
|
|
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
|
0.34 kg/m2
Standard Error 0.30
|
|
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
|
0.17 kg/m2
Standard Error 0.17
|
|
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
|
0.61 kg/m2
Standard Error 0.14
|
SECONDARY outcome
Timeframe: Throughout the study, up to Week 52Population: 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.)
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.
Outcome measures
| Measure |
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
n=124 Participants
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
n=132 Participants
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
SPB: not present → present (see description)
|
0 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
Myocardial Ischemia: not present → present
|
0 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
Tachycardia: ≥ 120 bpm and ↑ ≥ 15 bpm
|
1 particiapnts
|
1 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
Bradycardia: ≤ 50 bpm and ↓ 15 bpm
|
2 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
Sinus Tachycardia: ≥ 120 bpm and ↑ ≥ 15 bpm
|
1 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
Sinus Bradycardia: ≤ 50 bpm and ↓ 15 bpm
|
2 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
VPB: not present → present (see description)
|
2 particiapnts
|
1 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
Supraventricular Tachycardia: not present→ present
|
0 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
Ventricular Tachycardia: not present → present
|
0 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
Atrial Fibrillation (AF): not present → present
|
0 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
AF With Rapid Ventricular Response
|
0 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
Atrial Flutter: not present → present
|
0 particiapnts
|
1 particiapnts
|
|
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
|
0 particiapnts
|
|
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
|
0 particiapnts
|
|
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
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
Left Bundle Branch Block: not present → present
|
0 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
Right Bundle Branch Block: not present → present
|
6 particiapnts
|
4 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
Pre-excitation Syndrome: not present → present
|
0 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
Other Intraventricular Conduction: see description
|
0 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
Acute Infarction: not present → present
|
0 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
Subacute (recent) Infarction: not present→ present
|
0 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
Old Infarction: not present → present
|
1 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
Symmetrical T-Wave Inversions: not present→present
|
0 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
QTc Bazett: > 450 msec
|
5 particiapnts
|
6 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
QTc (.37): > 450 msec
|
0 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities Occurring During Double-Blind Treatment
QTc (.33): > 450 msec
|
0 particiapnts
|
1 particiapnts
|
SECONDARY outcome
Timeframe: Up to 52 WeeksPopulation: 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).
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.
Outcome measures
| Measure |
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
n=165 Participants
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
n=176 Participants
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment
Diastolic BP, standing-Increase (n=153,157)
|
6 participants
|
1 participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment
Heart Rate, supine-Decrease (n=160,168)
|
3 participants
|
0 participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment
Systolic BP, supine-Increase (n=160,168)
|
3 participants
|
1 participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment
Systolic BP, supine-Decrease (n=160,168)
|
7 participants
|
5 participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment
Systolic BP, standing-Increase (n=153, 157)
|
3 participants
|
0 participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment
Systolic BP, standing-Decrease (n=153,157)
|
2 participants
|
4 participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment
Diastolic BP, supine-Increase (n=160,168)
|
2 participants
|
0 participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment
Diastolic BP, supine-Decrease (n=160,168)
|
0 participants
|
3 participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment
Diastolic BP, standing-Decrease (n=153,157)
|
0 participants
|
1 participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment
Heart Rate, supine-Increase (n=160,168)
|
0 participants
|
0 participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment
Heart Rate, standing-Increase (n=153, 157)
|
4 participants
|
2 participants
|
|
Number of Participants With Potentially Clinically Relevant Vital Sign Abnormalities Occurring During Double-Blind Treatment
Heart Rate, standing-Decrease (n=153, 157)
|
1 participants
|
0 participants
|
SECONDARY outcome
Timeframe: Throughout Phase 2 of the study, up to Week 52Population: Phase 2 safety sample
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)
Outcome measures
| Measure |
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
n=165 Participants
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
n=176 Participants
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|
|
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
|
1 particiapnts
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
Uric acid (n=151, 157)
|
0 particiapnts
|
2 particiapnts
|
|
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
|
0 particiapnts
|
|
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
|
0 particiapnts
|
|
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
|
0 particiapnts
|
|
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
|
2 particiapnts
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
Creatine kinase (n=3, 1)
|
0 particiapnts
|
0 particiapnts
|
|
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
|
0 particiapnts
|
|
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
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
Prolactin (n=152, 158)
|
32 particiapnts
|
18 particiapnts
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
Cholesterol Total (n=151, 157)
|
22 particiapnts
|
28 particiapnts
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
Cholesterol Total (fasting) (n=126, 124)
|
17 particiapnts
|
25 particiapnts
|
|
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
|
7 particiapnts
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
Glucose Fasting Serum (n=126, 125)
|
15 particiapnts
|
13 particiapnts
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
HDL-C (n=151, 158)
|
53 particiapnts
|
38 particiapnts
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
HDL-C (fasting) (n=126, 125)
|
44 particiapnts
|
25 particiapnts
|
|
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
|
19 particiapnts
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
LDL-C (n=151, 157)
|
17 particiapnts
|
26 particiapnts
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
LDL-C (fasting) (n=126, 124)
|
14 particiapnts
|
22 particiapnts
|
|
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
|
5 particiapnts
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
Triglycerides (n=151, 157)
|
0 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
Triglycerides (fasting) (n=126, 124)
|
26 particiapnts
|
29 particiapnts
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
Triglycerides (non-fasting) (n=68, 75)
|
19 particiapnts
|
20 particiapnts
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
Sodium serum (n=152, 158)
|
1 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
Potassium serum (n=152, 158)
|
0 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
Chloride serum (n=152, 158)
|
0 particiapnts
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
Calcium (n=151, 157)
|
0 particiapnts
|
0 particiapnts
|
|
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
|
0 particiapnts
|
|
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
|
3 particiapnts
|
|
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
|
2 particiapnts
|
|
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
|
2 particiapnts
|
|
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
|
0 particiapnts
|
|
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
|
0 particiapnts
|
|
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
|
0 particiapnts
|
|
Number of Participants With Potentially Clinically Relevant Laboratory Abnormalities Occurring During Double-Blind Treatment (Phase 2)
Glucose urine (n=149, 155)
|
0 particiapnts
|
0 particiapnts
|
SECONDARY outcome
Timeframe: 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).
Outcome measures
| Measure |
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
n=787 Participants
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|
|
Summary of Concomitant Medications, Phase 1
Any central nervous system Medication
|
550 participants
|
—
|
|
Summary of Concomitant Medications, Phase 1
Analgesic
|
2 participants
|
—
|
|
Summary of Concomitant Medications, Phase 1
Anesthetic, general
|
1 participants
|
—
|
|
Summary of Concomitant Medications, Phase 1
Anesthetic, local
|
3 participants
|
—
|
|
Summary of Concomitant Medications, Phase 1
Anticholinergic
|
98 participants
|
—
|
|
Summary of Concomitant Medications, Phase 1
Antidepressant
|
12 participants
|
—
|
|
Summary of Concomitant Medications, Phase 1
Antiepileptic
|
48 participants
|
—
|
|
Summary of Concomitant Medications, Phase 1
Antimigraine prep
|
12 participants
|
—
|
|
Summary of Concomitant Medications, Phase 1
Antipsychotic
|
20 participants
|
—
|
|
Summary of Concomitant Medications, Phase 1
Anxiolytic
|
267 participants
|
—
|
|
Summary of Concomitant Medications, Phase 1
Hypnotic & Sedative
|
206 participants
|
—
|
|
Summary of Concomitant Medications, Phase 1
Opiod
|
78 participants
|
—
|
|
Summary of Concomitant Medications, Phase 1
Other Analgesic & Antipyretic
|
253 participants
|
—
|
|
Summary of Concomitant Medications, Phase 1
Other Nervous System Drug
|
1 participants
|
—
|
|
Summary of Concomitant Medications, Phase 1
Psychostimulant
|
2 participants
|
—
|
|
Summary of Concomitant Medications, Phase 1
Any extrapyramidal syndrome Medication
|
98 participants
|
—
|
|
Summary of Concomitant Medications, Phase 1
Benztropine
|
98 participants
|
—
|
SECONDARY outcome
Timeframe: 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).
Outcome measures
| Measure |
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
n=165 Participants
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
n=176 Participants
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|
|
Summary of Concomitant Medications, Phase 2
Any central nervous system Medication
|
120 participants
|
132 participants
|
|
Summary of Concomitant Medications, Phase 2
Anesthetic, local
|
1 participants
|
0 participants
|
|
Summary of Concomitant Medications, Phase 2
Anticholinergic
|
21 participants
|
25 participants
|
|
Summary of Concomitant Medications, Phase 2
Antidepressant
|
3 participants
|
1 participants
|
|
Summary of Concomitant Medications, Phase 2
Antiepileptic
|
8 participants
|
11 participants
|
|
Summary of Concomitant Medications, Phase 2
Antimigraine prep
|
1 participants
|
3 participants
|
|
Summary of Concomitant Medications, Phase 2
Antipsychotic
|
5 participants
|
3 participants
|
|
Summary of Concomitant Medications, Phase 2
Anxiolytic
|
63 participants
|
62 participants
|
|
Summary of Concomitant Medications, Phase 2
Hypnotic & Sedative
|
50 participants
|
41 participants
|
|
Summary of Concomitant Medications, Phase 2
Opiod
|
20 participants
|
14 participants
|
|
Summary of Concomitant Medications, Phase 2
Other Analgesic & Antipyretic
|
53 participants
|
66 participants
|
|
Summary of Concomitant Medications, Phase 2
Psychostimulant
|
0 participants
|
1 participants
|
|
Summary of Concomitant Medications, Phase 2
Any extrapyramidal syndrome Medication
|
25 participants
|
35 participants
|
|
Summary of Concomitant Medications, Phase 2
Benztropine
|
25 participants
|
35 participants
|
|
Summary of Concomitant Medications, Phase 2
Trihexyphenidyl
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Baseline, Weeks 8, 24, 36, 52Population: 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.
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.
Outcome measures
| Measure |
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
n=165 Participants
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
n=176 Participants
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|
|
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
|
-0.05 units on a scale
Standard Error 0.12
|
|
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 0.10
|
0.02 units on a scale
Standard Error 0.10
|
|
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
|
0.34 units on a scale
Standard Error 0.11
|
|
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
|
10.58 units on a scale
Standard Error 0.12
|
|
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 0.10
|
0.05 units on a scale
Standard Error 0.10
|
|
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
|
0.03 units on a scale
Standard Error 0.13
|
|
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
|
-0.14 units on a scale
Standard Error 0.10
|
SECONDARY outcome
Timeframe: Baseline, Weeks 8, 24, 36, 52Population: 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.
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.
Outcome measures
| Measure |
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
n=165 Participants
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
n=176 Participants
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|
|
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
|
0.06 units on a scale
Standard Error 0.06
|
|
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
|
0.14 units on a scale
Standard Error 0.07
|
|
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
|
0.04 units on a scale
Standard Error 0.05
|
|
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
|
0.13 units on a scale
Standard Error 0.07
|
|
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
|
-0.05 units on a scale
Standard Error 0.04
|
|
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
|
-0.01 units on a scale
Standard Error 0.06
|
|
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
|
0.14 units on a scale
Standard Error 0.07
|
SECONDARY outcome
Timeframe: Baseline, Weeks 8, 24, 36, 52Population: 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.
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.
Outcome measures
| Measure |
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
n=165 Participants
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
n=176 Participants
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|
|
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
|
0.27 units on a scale
Standard Error 0.05
|
|
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
|
0.04 units on a scale
Standard Error 0.05
|
|
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
|
-0.06 units on a scale
Standard Error 0.05
|
|
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
|
-0.18 units on a scale
Standard Error 0.04
|
|
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
|
-0.17 units on a scale
Standard Error 0.04
|
|
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
|
-0.05 units on a scale
Standard Error 0.04
|
|
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
|
0.15 units on a scale
Standard Error 0.05
|
Adverse Events
Phase 1: Single-Blind Treatment, Lamotrigine + Aripiprazole
Serious events: 32 serious events
Other events: 545 other events
Deaths: 0 deaths
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
Serious events: 9 serious events
Other events: 61 other events
Deaths: 0 deaths
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
Serious events: 5 serious events
Other events: 74 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase 1: Single-Blind Treatment, Lamotrigine + Aripiprazole
n=787 participants at risk
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 1 (all subjects) - up to 24 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
n=165 participants at risk
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
n=176 participants at risk
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|---|
|
Cardiac disorders
CARDIAC DISORDER
|
0.00%
0/787
|
0.00%
0/165
|
0.57%
1/176
|
|
Cardiac disorders
VENTRICULAR FIBRILLATION
|
0.00%
0/787
|
0.61%
1/165
|
0.00%
0/176
|
|
Cardiac disorders
WOLFF-PARKINSON-WHITE SYNDROME
|
0.00%
0/787
|
0.61%
1/165
|
0.00%
0/176
|
|
Vascular disorders
HYPERTENSION
|
0.00%
0/787
|
0.61%
1/165
|
0.00%
0/176
|
|
Social circumstances
PHYSICAL ASSAULT
|
0.13%
1/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Psychiatric disorders
MANIA
|
0.38%
3/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Psychiatric disorders
ANXIETY
|
0.13%
1/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Psychiatric disorders
AGITATION
|
0.13%
1/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Psychiatric disorders
DEPRESSION
|
0.38%
3/787
|
0.00%
0/165
|
0.57%
1/176
|
|
Psychiatric disorders
PANIC ATTACK
|
0.13%
1/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Psychiatric disorders
BIPOLAR DISORDER
|
0.25%
2/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Psychiatric disorders
COMPLETED SUICIDE
|
0.13%
1/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Psychiatric disorders
SUICIDAL IDEATION
|
1.0%
8/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Psychiatric disorders
BIPOLAR I DISORDER
|
0.25%
2/787
|
1.2%
2/165
|
0.57%
1/176
|
|
Psychiatric disorders
DEPRESSIVE SYMPTOM
|
0.25%
2/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Psychiatric disorders
HOMICIDAL IDEATION
|
0.25%
2/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Psychiatric disorders
MENTAL STATUS CHANGES
|
0.00%
0/787
|
0.00%
0/165
|
0.57%
1/176
|
|
Nervous system disorders
AKATHISIA
|
0.13%
1/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Nervous system disorders
DIZZINESS
|
0.00%
0/787
|
0.61%
1/165
|
0.00%
0/176
|
|
Nervous system disorders
ALTERED STATE OF CONSCIOUSNESS
|
0.13%
1/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Gastrointestinal disorders
INGUINAL HERNIA
|
0.00%
0/787
|
0.61%
1/165
|
0.00%
0/176
|
|
Gastrointestinal disorders
GASTRITIS EROSIVE
|
0.13%
1/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Gastrointestinal disorders
MALLORY-WEISS SYNDROME
|
0.13%
1/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Renal and urinary disorders
NEPHROLITHIASIS
|
0.00%
0/787
|
0.61%
1/165
|
0.00%
0/176
|
|
Metabolism and nutrition disorders
OBESITY
|
0.00%
0/787
|
0.00%
0/165
|
0.57%
1/176
|
|
Blood and lymphatic system disorders
ANAEMIA
|
0.00%
0/787
|
0.61%
1/165
|
0.00%
0/176
|
|
Reproductive system and breast disorders
MENSTRUAL DISORDER
|
0.13%
1/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Reproductive system and breast disorders
OVARIAN CYST RUPTURED
|
0.13%
1/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Injury, poisoning and procedural complications
HEAD INJURY
|
0.13%
1/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Injury, poisoning and procedural complications
INTENTIONAL OVERDOSE
|
0.00%
0/787
|
0.61%
1/165
|
0.00%
0/176
|
|
Injury, poisoning and procedural complications
ROAD TRAFFIC ACCIDENT
|
0.13%
1/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Pregnancy, puerperium and perinatal conditions
PREGNANCY
|
0.00%
0/787
|
0.61%
1/165
|
0.00%
0/176
|
|
General disorders
CHEST PAIN
|
0.38%
3/787
|
1.2%
2/165
|
0.00%
0/176
|
|
General disorders
NON-CARDIAC CHEST PAIN
|
0.13%
1/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
VULVAL CANCER
|
0.13%
1/787
|
0.00%
0/165
|
0.00%
0/176
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
UTERINE LEIOMYOMA
|
0.13%
1/787
|
0.00%
0/165
|
0.00%
0/176
|
Other adverse events
| Measure |
Phase 1: Single-Blind Treatment, Lamotrigine + Aripiprazole
n=787 participants at risk
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 1 (all subjects) - up to 24 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Placebo
n=165 participants at risk
Lamotrigine 100-200 mg/day, Placebo 0 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks
|
Phase 2 Double-Blind Treatment: Lamotrigine + Aripiprazole
n=176 participants at risk
Lamotrigine 100-200 mg/day, Aripiprazole 10-30 mg/day: tablets, oral, once daily, Phase 2 - up to 52 weeks.
|
|---|---|---|---|
|
Psychiatric disorders
ANXIETY
|
9.3%
73/787
|
3.6%
6/165
|
7.4%
13/176
|
|
Psychiatric disorders
INSOMNIA
|
17.5%
138/787
|
11.5%
19/165
|
7.4%
13/176
|
|
Psychiatric disorders
AGITATION
|
8.3%
65/787
|
4.8%
8/165
|
6.2%
11/176
|
|
Psychiatric disorders
RESTLESSNESS
|
7.0%
55/787
|
1.2%
2/165
|
1.7%
3/176
|
|
Nervous system disorders
HEADACHE
|
11.7%
92/787
|
7.9%
13/165
|
4.5%
8/176
|
|
Nervous system disorders
SEDATION
|
7.9%
62/787
|
1.8%
3/165
|
0.57%
1/176
|
|
Nervous system disorders
AKATHISIA
|
24.9%
196/787
|
6.1%
10/165
|
10.8%
19/176
|
|
Nervous system disorders
DIZZINESS
|
5.1%
40/787
|
1.8%
3/165
|
1.1%
2/176
|
|
Nervous system disorders
SOMNOLENCE
|
5.3%
42/787
|
0.00%
0/165
|
0.57%
1/176
|
|
Gastrointestinal disorders
NAUSEA
|
13.1%
103/787
|
3.6%
6/165
|
4.0%
7/176
|
|
Gastrointestinal disorders
VOMITING
|
5.1%
40/787
|
0.61%
1/165
|
0.57%
1/176
|
|
Gastrointestinal disorders
DRY MOUTH
|
5.6%
44/787
|
1.8%
3/165
|
2.3%
4/176
|
|
Infections and infestations
URINARY TRACT INFECTION
|
4.4%
35/787
|
5.5%
9/165
|
2.8%
5/176
|
|
Infections and infestations
UPPER RESPIRATORY TRACT INFECTION
|
4.3%
34/787
|
7.9%
13/165
|
6.8%
12/176
|
|
Musculoskeletal and connective tissue disorders
BACK PAIN
|
3.3%
26/787
|
3.0%
5/165
|
5.1%
9/176
|
|
General disorders
FATIGUE
|
9.4%
74/787
|
0.61%
1/165
|
2.8%
5/176
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
- Publication restrictions are in place
Restriction type: OTHER