Trial Outcomes & Findings for Lamictal as Add-on Treatment for Bipolar I Disorder in Pediatric Patients (NCT NCT00723450)
NCT ID: NCT00723450
Last Updated: 2017-01-09
Results Overview
TOBE was defined by the first prescription of any additional pharmacotherapy to treat bipolar symptoms, increasing the dose(s) of the participants conventional bipolar medication(s), treatment with electroconvulsive therapy, or moving the participant to a more restricted environment for observation, safety, or treatment; or participant withdrawal from the study due to a bipolar-related adverse event (AE) or serious adverse event (SAE); or participants withdrawal from the study due to lack of efficacy as defined by rating scale threshold scores. TOBE was calculated using a log rank test with stratification for index mood state (depression, mania/hypomania, mixed mood).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
301 participants
Primary outcome timeframe
From randomization until Week 36
Results posted on
2017-01-09
Participant Flow
A total of 301 participants were enrolled in the study, of which 298 subjects took at least one dose of lamotrigine (LTG). One hundred and seventy three participants met stabilization criteria and entered the Randomized Phase.
The study consisted of a 2-week Screening Phase, an 18-week Open-Label Phase, a 36-week Double-Blind Randomized Phase and a Taper and Follow-up Phase (up to 4 weeks depending on the dose the participant was taking at the last Open-Label or Randomized Phase visit), which was either open-label or double-blind depending on the phase of the study.
Participant milestones
| Measure |
LTG: Open-Label Phase
Participants (par.) received lamotrigine (LTG) up to a maximum dose depending on their age and concomitant bipolar medication group. Participants 10 -12 years of age received LTG up to a maximum dose of: 3 milligrams/kilograms (mg/kg)/day or 100 mg/day, whichever was less; or 6 mg/kg/day or 200 mg/day whichever was less; or 12 mg/kg/day or 300 mg/day whichever was less, depending on their bipolar medication group. Participants 13-17 years of age received LTG up to a maximum dose of 150 mg/day, 300 mg/day, or 400 mg/day depending on their bipolar medication group. Participants took LTG for a duration of up to 18 weeks.
|
Placebo
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|---|
|
Randomized Phase
NOT COMPLETED
|
0
|
65
|
67
|
|
Open-Label Phase
STARTED
|
298
|
0
|
0
|
|
Open-Label Phase
COMPLETED
|
173
|
0
|
0
|
|
Open-Label Phase
NOT COMPLETED
|
125
|
0
|
0
|
|
Randomized Phase
STARTED
|
0
|
86
|
87
|
|
Randomized Phase
COMPLETED
|
0
|
21
|
20
|
Reasons for withdrawal
| Measure |
LTG: Open-Label Phase
Participants (par.) received lamotrigine (LTG) up to a maximum dose depending on their age and concomitant bipolar medication group. Participants 10 -12 years of age received LTG up to a maximum dose of: 3 milligrams/kilograms (mg/kg)/day or 100 mg/day, whichever was less; or 6 mg/kg/day or 200 mg/day whichever was less; or 12 mg/kg/day or 300 mg/day whichever was less, depending on their bipolar medication group. Participants 13-17 years of age received LTG up to a maximum dose of 150 mg/day, 300 mg/day, or 400 mg/day depending on their bipolar medication group. Participants took LTG for a duration of up to 18 weeks.
|
Placebo
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|---|
|
Open-Label Phase
Adverse Event
|
26
|
0
|
0
|
|
Open-Label Phase
Lack of Efficacy
|
18
|
0
|
0
|
|
Open-Label Phase
Protocol Violation
|
35
|
0
|
0
|
|
Open-Label Phase
Lost to Follow-up
|
7
|
0
|
0
|
|
Open-Label Phase
Physician Decision
|
2
|
0
|
0
|
|
Open-Label Phase
Withdrawal by Subject
|
37
|
0
|
0
|
|
Randomized Phase
Adverse Event
|
0
|
26
|
17
|
|
Randomized Phase
Lack of Efficacy
|
0
|
11
|
11
|
|
Randomized Phase
Protocol Violation
|
0
|
9
|
13
|
|
Randomized Phase
Lost to Follow-up
|
0
|
2
|
3
|
|
Randomized Phase
Physician Decision
|
0
|
3
|
1
|
|
Randomized Phase
Withdrawal by Subject
|
0
|
14
|
22
|
Baseline Characteristics
Lamictal as Add-on Treatment for Bipolar I Disorder in Pediatric Patients
Baseline characteristics by cohort
| Measure |
Placebo
n=86 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
n=87 Participants
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Total
n=173 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
13.5 Years
STANDARD_DEVIATION 2.22 • n=5 Participants
|
13.4 Years
STANDARD_DEVIATION 2.33 • n=7 Participants
|
13.5 Years
STANDARD_DEVIATION 2.27 • n=5 Participants
|
|
Gender
Female
|
39 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
72 Participants
n=5 Participants
|
|
Gender
Male
|
47 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
101 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage
|
9 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Asian - East Asian Heritage
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White - Arabic/North African Heritage
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White - White/Caucasian/European Heritage
|
71 Participants
n=5 Participants
|
71 Participants
n=7 Participants
|
142 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Mixed Race
|
4 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: From randomization until Week 36Population: Randomized Intent-to-Treat (ITT) Population: all participants who were randomized to LTG or placebo and received at least one dose of investigational product.
TOBE was defined by the first prescription of any additional pharmacotherapy to treat bipolar symptoms, increasing the dose(s) of the participants conventional bipolar medication(s), treatment with electroconvulsive therapy, or moving the participant to a more restricted environment for observation, safety, or treatment; or participant withdrawal from the study due to a bipolar-related adverse event (AE) or serious adverse event (SAE); or participants withdrawal from the study due to lack of efficacy as defined by rating scale threshold scores. TOBE was calculated using a log rank test with stratification for index mood state (depression, mania/hypomania, mixed mood).
Outcome measures
| Measure |
Placebo
n=86 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
n=87 Participants
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Time From Randomization to the Occurrence of a Bipolar Event (TOBE)
Stratum: Depression, n=22,21
|
50 Days
Standard Error 3.8
|
155 Days
Standard Error 14.7
|
|
Time From Randomization to the Occurrence of a Bipolar Event (TOBE)
Stratum: Mania/Hypomania, n=36, 37
|
120 Days
Standard Error 12.2
|
163 Days
Standard Error 12.2
|
|
Time From Randomization to the Occurrence of a Bipolar Event (TOBE)
Stratum: Mixed Mood, n=28, 29
|
107 Days
Standard Error 13.8
|
136 Days
Standard Error 15.4
|
SECONDARY outcome
Timeframe: From randomization until withdrawal from the study for any cause (up to Week 36)Population: Randomized ITT Population
The time from randomization to the withdrawal from study was analyzed. TTW was calculated using the log rank test with stratification for index mood state (depression, mania/hypomania, mixed mood).
Outcome measures
| Measure |
Placebo
n=86 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
n=87 Participants
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Time From Randomization to Withdrawal From the Study for Any Cause (TTW)
Stratum: Depression, n=22, 21
|
113 Days
Standard Error 21.4
|
141 Days
Standard Error 20.0
|
|
Time From Randomization to Withdrawal From the Study for Any Cause (TTW)
Stratum: Mania/Hypomania, n=36, 37
|
138 Days
Standard Error 17.3
|
144 Days
Standard Error 15.6
|
|
Time From Randomization to Withdrawal From the Study for Any Cause (TTW)
Stratum: Mixed Mood, n=28, 29
|
101 Days
Standard Error 15.7
|
106 Days
Standard Error 16.3
|
SECONDARY outcome
Timeframe: From randomization until intervention administered for a mood episode (up to Week 36)Population: Randomized ITT Population
The time from randomization to the intervention for a mood episode (depression, mania/hypomania or mixed mood) was analyzed. TIME was calculated using the log rank test with stratification for index mood state (depression, mania/hypomania, mixed mood).
Outcome measures
| Measure |
Placebo
n=86 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
n=87 Participants
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Time From Randomization to Intervention for a Mood Episode (TIME)
Stratum: Depression, n=22, 21
|
62 Days
Standard Error 5.2
|
164 Days
Standard Error 12.7
|
|
Time From Randomization to Intervention for a Mood Episode (TIME)
Stratum: Mania/Hypomania, n=36, 37
|
129 Days
Standard Error 11.7
|
179 Days
Standard Error 10.8
|
|
Time From Randomization to Intervention for a Mood Episode (TIME)
Stratum: Mixed Mood, n=28, 29
|
120 Days
Standard Error 13.7
|
127 Days
Standard Error 12.0
|
SECONDARY outcome
Timeframe: From randomization until intervention administered for depression, mania/hypomania or a mixed episode (up to Week 36)Population: Randomized ITT Population
The time from randomization to intervention for depression (TIDep), mania/hypomania (TIMan), or a mixed episode (TIMix) was analyzed. TIDep, TIMan, and TIMix were calculated using the log rank test with stratification for index mood state (depression, mania/hypomania, mixed mood).
Outcome measures
| Measure |
Placebo
n=86 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
n=87 Participants
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix)
TIDep: Depression, n=22, 21
|
61 Days
Standard Error 1.5
|
46 Days
Standard Error 1.5
|
|
Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix)
TIDep: Mania/Hypomania, n=36, 37
|
NA Days
Standard Error NA
There were zero events for this endpoint in this stratum, therefore, the mean and the standard error could not be estimated.
|
NA Days
Standard Error NA
There were zero events for this endpoint in this stratum, therefore, the mean and the standard error could not be estimated.
|
|
Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix)
TIDep: Mixed Mood, n=28, 29
|
59 Days
Standard Error 2.6
|
159 Days
Standard Error NA
There were 0-1 events for this endpoint in this stratum, therefore, the standard error could not be estimated.
|
|
Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix)
TIMan: Depression, n=22, 21
|
74 Days
Standard Error 3.9
|
182 Days
Standard Error NA
There were 0-1 events for this endpoint in this stratum, therefore, the standard error could not be estimated.
|
|
Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix)
TIMan: Mania/Hypomania, n=36, 37
|
139 Days
Standard Error 11.5
|
61 Days
Standard Error 2.1
|
|
Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix)
TIMan: Mixed Mood, n=28, 29
|
105 Days
Standard Error 7.3
|
148 Days
Standard Error 8.5
|
|
Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix)
TIMix: Depression, n=22, 21
|
37 Days
Standard Error 1.3
|
158 Days
Standard Error NA
There were 0-1 events for this endpoint in this stratum, therefore, the standard error could not be estimated.
|
|
Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix)
TIMix: Mania/Hypomania, n=36, 37
|
135 Days
Standard Error 6.3
|
194 Days
Standard Error 7.5
|
|
Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix)
TIMix: Mixed Mood, n=28, 29
|
160 Days
Standard Error 10.7
|
57 Days
Standard Error 2.5
|
SECONDARY outcome
Timeframe: From randomization until a relapse/recurrence to depression, mania/hypomania, or mixed mood state (up to Week 36)Population: Randomized ITT Population. Only those participants requiring intervention to treat either the emergence of, or a change, in bipolar symptoms were analyzed.
The number of participants requiring intervention to treat either the emergence of or a change in bipolar symptoms that is, experiencing a relapse/recurrence to depression, mania/hypomania, or mixed mood state were analyzed.
Outcome measures
| Measure |
Placebo
n=31 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
n=18 Participants
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Number of Participants Experiencing a Relapse/Recurrence to Depression, Mania/Hypomania, or Mixed Mood State
Depression
|
5 Participants
|
3 Participants
|
|
Number of Participants Experiencing a Relapse/Recurrence to Depression, Mania/Hypomania, or Mixed Mood State
Mania/hypomania
|
16 Participants
|
6 Participants
|
|
Number of Participants Experiencing a Relapse/Recurrence to Depression, Mania/Hypomania, or Mixed Mood State
Mixed episode state
|
10 Participants
|
9 Participants
|
SECONDARY outcome
Timeframe: From randomization up to Week 36Population: Randomized ITT Population. Only those participants requiring intervention to treat either the emergence of, or a change, in bipolar symptoms were analyzed.
The proportion of participants (par.) requiring intervention to treat either the emergence of or a change in bipolar symptoms, that is, experiencing a relapse/recurrence to depression, mania/hypomania, or mixed mood state at any time within the first 30, 90, and 180 days in the Randomized Phase were analyzed.
Outcome measures
| Measure |
Placebo
n=31 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
n=18 Participants
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Number of Participants Experiencing a Relapse/Recurrence Within the First 30, 90, and 180 Days in the Randomized Phase
Mania/hypomania, 30 days, n=16, 6
|
9 Participants
|
2 Participants
|
|
Number of Participants Experiencing a Relapse/Recurrence Within the First 30, 90, and 180 Days in the Randomized Phase
Mania/hypomania, 90 days, n=16, 6
|
12 Participants
|
4 Participants
|
|
Number of Participants Experiencing a Relapse/Recurrence Within the First 30, 90, and 180 Days in the Randomized Phase
Mania/hypomania, 180 days, n=16, 6
|
16 Participants
|
5 Participants
|
|
Number of Participants Experiencing a Relapse/Recurrence Within the First 30, 90, and 180 Days in the Randomized Phase
Depression, 30 days, n=5, 3
|
1 Participants
|
1 Participants
|
|
Number of Participants Experiencing a Relapse/Recurrence Within the First 30, 90, and 180 Days in the Randomized Phase
Depression, 90 days, n=5, 3
|
5 Participants
|
2 Participants
|
|
Number of Participants Experiencing a Relapse/Recurrence Within the First 30, 90, and 180 Days in the Randomized Phase
Depression, 180 days, n=5, 3
|
5 Participants
|
3 Participants
|
|
Number of Participants Experiencing a Relapse/Recurrence Within the First 30, 90, and 180 Days in the Randomized Phase
Mixed mood state, 30 days, n= 10, 9
|
3 Participants
|
2 Participants
|
|
Number of Participants Experiencing a Relapse/Recurrence Within the First 30, 90, and 180 Days in the Randomized Phase
Mixed mood state, 90 days, n= 10, 9
|
7 Participants
|
6 Participants
|
|
Number of Participants Experiencing a Relapse/Recurrence Within the First 30, 90, and 180 Days in the Randomized Phase
Mixed mood state, 180 days, n= 10, 9
|
10 Participants
|
8 Participants
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18Population: Open-Label ITT population: all participants who entered the Open-Label Phase and received at least one dose of LTG.
The QIDS-A17-C is a 17-item scale used to assess depression severity in adolescents according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) diagnostic criteria for a major depressive episode; it is a modified version of the Quick Inventory of Depressive Symptomatology (QIDS) used for adults. Each item is scored on a 0-3 scale, yielding 9 domain scores. The range of scores is 0 (best possible outcome) to 27 (worst possible outcome). Analysis was performed using mixed model repeated measures.
Outcome measures
| Measure |
Placebo
n=298 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Open-Label Phase
Week 1
|
-2.1 Scores on a Scale
Standard Error 0.22
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Open-Label Phase
Week 2
|
-2.9 Scores on a Scale
Standard Error 0.28
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Open-Label Phase
Week 3
|
-3.7 Scores on a Scale
Standard Error 0.28
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Open-Label Phase
Week 4
|
-3.8 Scores on a Scale
Standard Error 0.30
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Open-Label Phase
Week 5
|
-4.3 Scores on a Scale
Standard Error 0.30
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Open-Label Phase
Week 6
|
-4.7 Scores on a Scale
Standard Error 0.30
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Open-Label Phase
Week 7
|
-5.1 Scores on a Scale
Standard Error 0.30
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Open-Label Phase
Week 8
|
-4.9 Scores on a Scale
Standard Error 0.31
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Open-Label Phase
Week 9
|
-5.6 Scores on a Scale
Standard Error 0.30
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Open-Label Phase
Week 10
|
-6.1 Scores on a Scale
Standard Error 0.29
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Open-Label Phase
Week 11
|
-6.4 Scores on a Scale
Standard Error 0.30
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Open-Label Phase
Week 12
|
-6.6 Scores on a Scale
Standard Error 0.32
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Open-Label Phase
Week 13
|
-6.7 Scores on a Scale
Standard Error 0.32
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Open-Label Phase
Week 14
|
-6.8 Scores on a Scale
Standard Error 0.34
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Open-Label Phase
Week 15
|
-6.8 Scores on a Scale
Standard Error 0.40
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Open-Label Phase
Week 16
|
-6.8 Scores on a Scale
Standard Error 0.41
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Open-Label Phase
Week 17
|
-6.5 Scores on a Scale
Standard Error 0.53
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Open-Label Phase
Week 18
|
-6.5 Scores on a Scale
Standard Error 0.70
|
—
|
SECONDARY outcome
Timeframe: Randomization and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, and 36Population: Randomized ITT Population
The QIDS-A17-C is a 17-item scale used to assess depression severity in adolescents according to the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) diagnostic criteria for a major depressive episode; it is a modified version of the Quick Inventory of Depressive Symptomatology (QIDS) used for adults. Each item is scored on a 0-3 scale, yielding 9 domain scores. The range of scores is 0 (best possible outcome) to 27 (worst possible outcome). Analysis was performed using mixed model repeated measures.
Outcome measures
| Measure |
Placebo
n=86 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
n=87 Participants
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Randomized Phase
Week 1
|
0.8 Scores on a scale
Standard Error 0.30
|
0.5 Scores on a scale
Standard Error 0.31
|
|
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Randomized Phase
Week 2
|
1.5 Scores on a scale
Standard Error 0.37
|
1.1 Scores on a scale
Standard Error 0.37
|
|
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Randomized Phase
Week 3
|
1.3 Scores on a scale
Standard Error 0.36
|
0.6 Scores on a scale
Standard Error 0.36
|
|
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Randomized Phase
Week 4
|
1.2 Scores on a scale
Standard Error 0.39
|
1.0 Scores on a scale
Standard Error 0.39
|
|
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Randomized Phase
Week 6
|
1.9 Scores on a scale
Standard Error 0.49
|
1.5 Scores on a scale
Standard Error 0.47
|
|
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Randomized Phase
Week 8
|
1.9 Scores on a scale
Standard Error 0.47
|
1.7 Scores on a scale
Standard Error 0.45
|
|
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Randomized Phase
Week 10
|
1.4 Scores on a scale
Standard Error 0.44
|
1.5 Scores on a scale
Standard Error 0.41
|
|
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Randomized Phase
Week 12
|
1.4 Scores on a scale
Standard Error 0.40
|
1.2 Scores on a scale
Standard Error 0.39
|
|
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Randomized Phase
Week 16
|
2.2 Scores on a scale
Standard Error 0.48
|
1.8 Scores on a scale
Standard Error 0.47
|
|
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Randomized Phase
Week 20
|
1.5 Scores on a scale
Standard Error 0.50
|
2.5 Scores on a scale
Standard Error 0.46
|
|
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Randomized Phase
Week 24
|
1.7 Scores on a scale
Standard Error 0.53
|
1.8 Scores on a scale
Standard Error 0.51
|
|
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Randomized Phase
Week 28
|
1.6 Scores on a scale
Standard Error 0.61
|
2.3 Scores on a scale
Standard Error 0.57
|
|
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Randomized Phase
Week 32
|
1.0 Scores on a scale
Standard Error 0.72
|
1.9 Scores on a scale
Standard Error 0.72
|
|
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Clinician Interview, Semi-structured, Adolescent Version (QIDS- A17-C) at Each Visit in the Randomized Phase
Week 36
|
2.3 Scores on a scale
Standard Error 0.63
|
1.9 Scores on a scale
Standard Error 0.63
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, and 18Population: Open-Label ITT Population
The QIDS-A17-SR is a 17-item scale used to assess depression severity in adolescents according to the DSM-IV-TR diagnostic criteria for a major depressive episode; it is a modified version of the Quick Inventory of Depressive Symptomatology (QIDS) used for adults. Each item is scored on a 0-3 scale, yielding 9 domain scores. The range of scores is 0 (best possible outcome) to 27 (worst possible outcome). The scale is completed by the participant. Analysis was performed using mixed model repeated measures.
Outcome measures
| Measure |
Placebo
n=298 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Self-report Adolescent Version (QIDS-A17-SR) at Each Visit in the Open-Label Phase
Week 4
|
-2.7 Scores on a scale
Standard Error 0.25
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Self-report Adolescent Version (QIDS-A17-SR) at Each Visit in the Open-Label Phase
Week 8
|
-3.3 Scores on a scale
Standard Error 0.27
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Self-report Adolescent Version (QIDS-A17-SR) at Each Visit in the Open-Label Phase
Week 12
|
-4.3 Scores on a scale
Standard Error 0.28
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Self-report Adolescent Version (QIDS-A17-SR) at Each Visit in the Open-Label Phase
Week 16
|
-4.5 Scores on a scale
Standard Error 0.33
|
—
|
|
Change From Baseline in the Quick Inventory of Depressive Symptomatology - Self-report Adolescent Version (QIDS-A17-SR) at Each Visit in the Open-Label Phase
Week 18
|
-5.0 Scores on a scale
Standard Error 0.52
|
—
|
SECONDARY outcome
Timeframe: Randomization and Weeks 8, 16, 24, 32, and 36Population: Randomized ITT Population
The QIDS-A17-SR is a 17-item scale used to assess depression severity in adolescents according to the DSM-IV-TR diagnostic criteria for a major depressive episode; it is a modified version of the Quick Inventory of Depressive Symptomatology (QIDS) used for adults. Each item is scored on a 0-3 scale, yielding 9 domain scores. The range of scores is 0 (best possible outcome) to 27 (worst possible outcome). The scale is completed by the participant. Analysis was performed using mixed model repeated measures.
Outcome measures
| Measure |
Placebo
n=86 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
n=87 Participants
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Self-report Adolescent Version (QIDS-A17-SR) at Each Visit in the Randomized Phase
Week 8
|
1.6 Scores on a scale
Standard Error 0.47
|
1.2 Scores on a scale
Standard Error 0.48
|
|
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Self-report Adolescent Version (QIDS-A17-SR) at Each Visit in the Randomized Phase
Week 16
|
1.6 Scores on a scale
Standard Error 0.60
|
1.4 Scores on a scale
Standard Error 0.58
|
|
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Self-report Adolescent Version (QIDS-A17-SR) at Each Visit in the Randomized Phase
Week 24
|
1.0 Scores on a scale
Standard Error 0.60
|
1.5 Scores on a scale
Standard Error 0.56
|
|
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Self-report Adolescent Version (QIDS-A17-SR) at Each Visit in the Randomized Phase
Week 32
|
0.6 Scores on a scale
Standard Error 0.66
|
0.2 Scores on a scale
Standard Error 0.63
|
|
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Self-report Adolescent Version (QIDS-A17-SR) at Each Visit in the Randomized Phase
Week 36
|
0.9 Scores on a scale
Standard Error 0.66
|
0.8 Scores on a scale
Standard Error 0.68
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18Population: Open-Label ITT Population
Severity of the bipolar illness was based on the CGI-BP(S) score which had a range from 1 (normal, not ill) to 7 (very severely ill). Analysis was performed using mixed model repeated measures.
Outcome measures
| Measure |
Placebo
n=298 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase
Week 1
|
-0.4 Scores on a scale
Standard Error 0.05
|
—
|
|
Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase
Week 2
|
-0.6 Scores on a scale
Standard Error 0.05
|
—
|
|
Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase
Week 3
|
-0.9 Scores on a scale
Standard Error 0.06
|
—
|
|
Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase
Week 4
|
-1.0 Scores on a scale
Standard Error 0.06
|
—
|
|
Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase
Week 5
|
-1.2 Scores on a scale
Standard Error 0.06
|
—
|
|
Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase
Week 6
|
-1.3 Scores on a scale
Standard Error 0.06
|
—
|
|
Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase
Week 7
|
-1.4 Scores on a scale
Standard Error 0.07
|
—
|
|
Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase
Week 8
|
-1.5 Scores on a scale
Standard Error 0.07
|
—
|
|
Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase
Week 9
|
-1.6 Scores on a scale
Standard Error 0.07
|
—
|
|
Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase
Week 10
|
-1.8 Scores on a scale
Standard Error 0.07
|
—
|
|
Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase
Week 11
|
-1.9 Scores on a scale
Standard Error 0.07
|
—
|
|
Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase
Week 12
|
-2.1 Scores on a scale
Standard Error 0.07
|
—
|
|
Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase
Week 13
|
-2.1 Scores on a scale
Standard Error 0.07
|
—
|
|
Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase
Week 14
|
-2.1 Scores on a scale
Standard Error 0.07
|
—
|
|
Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase
Week 15
|
-2.1 Scores on a scale
Standard Error 0.08
|
—
|
|
Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase
Week 16
|
-2.1 Scores on a scale
Standard Error 0.10
|
—
|
|
Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase
Week 17
|
-2.0 Scores on a scale
Standard Error 0.12
|
—
|
|
Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase
Week 18
|
-2.1 Scores on a scale
Standard Error 0.15
|
—
|
SECONDARY outcome
Timeframe: Randomization and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, and 36Population: Randomized ITT Population
Severity of the bipolar illness was based on the CGI-BP(S) score which had a range from 1 (normal, not ill) to 7 (very severely ill). Analysis was performed using mixed model repeated measures.
Outcome measures
| Measure |
Placebo
n=86 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
n=87 Participants
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase
Week 1
|
0.2 Scores on a scale
Standard Error 0.09
|
0.0 Scores on a scale
Standard Error 0.09
|
|
Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase
Week 2
|
0.4 Scores on a scale
Standard Error 0.12
|
0.2 Scores on a scale
Standard Error 0.12
|
|
Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase
Week 3
|
0.4 Scores on a scale
Standard Error 0.12
|
0.2 Scores on a scale
Standard Error 0.12
|
|
Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase
Week 4
|
0.6 Scores on a scale
Standard Error 0.13
|
0.3 Scores on a scale
Standard Error 0.13
|
|
Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase
Week 6
|
0.8 Scores on a scale
Standard Error 0.15
|
0.4 Scores on a scale
Standard Error 0.15
|
|
Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase
Week 8
|
0.7 Scores on a scale
Standard Error 0.15
|
0.4 Scores on a scale
Standard Error 0.14
|
|
Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase
Week 10
|
0.4 Scores on a scale
Standard Error 0.13
|
0.6 Scores on a scale
Standard Error 0.13
|
|
Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase
Week 12
|
0.5 Scores on a scale
Standard Error 0.14
|
0.4 Scores on a scale
Standard Error 0.14
|
|
Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase
Week 16
|
0.6 Scores on a scale
Standard Error 0.17
|
0.6 Scores on a scale
Standard Error 0.15
|
|
Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase
Week 20
|
0.5 Scores on a scale
Standard Error 0.17
|
0.8 Scores on a scale
Standard Error 0.16
|
|
Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase
Week 24
|
0.4 Scores on a scale
Standard Error 0.17
|
0.6 Scores on a scale
Standard Error 0.16
|
|
Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase
Week 28
|
0.3 Scores on a scale
Standard Error 0.17
|
0.5 Scores on a scale
Standard Error 0.16
|
|
Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase
Week 32
|
0.2 Scores on a scale
Standard Error 0.19
|
0.5 Scores on a scale
Standard Error 0.20
|
|
Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase
Week 36
|
0.4 Scores on a scale
Standard Error 0.19
|
0.3 Scores on a scale
Standard Error 0.21
|
SECONDARY outcome
Timeframe: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18Population: Open-Label ITT Population. Only those par. available at the specified time points were analyzed (represented by n=X). Different par. may have been analyzed at different time points, so the overall number of par. analyzed reflects everyone in the Open-Label Population.
Improvement of bipolar illness was based on the CGI-BP (I) score which ranged from 1 (very much improved) to 7 (very much worse). Analysis was performed using mixed model repeated measures.
Outcome measures
| Measure |
Placebo
n=298 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase
Week 1, n=290
|
3.6 Scores on a scale
Standard Deviation 0.80
|
—
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase
Week 2, n=278
|
3.3 Scores on a scale
Standard Deviation 0.90
|
—
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase
Week 3, n=270
|
3.1 Scores on a scale
Standard Deviation 0.96
|
—
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase
Week 4, n=265
|
3.0 Scores on a scale
Standard Deviation 1.03
|
—
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase
Week 5, n=258
|
2.8 Scores on a scale
Standard Deviation 1.01
|
—
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase
Week 6, n=243
|
2.7 Scores on a scale
Standard Deviation 1.05
|
—
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase
Week 7, n=246
|
2.5 Scores on a scale
Standard Deviation 1.07
|
—
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase
Week 8, n=236
|
2.5 Scores on a scale
Standard Deviation 1.09
|
—
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase
Week 9, n=227
|
2.3 Scores on a scale
Standard Deviation 1.05
|
—
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase
Week 10, n=205
|
2.2 Scores on a scale
Standard Deviation 1.09
|
—
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase
Week 11, n=181
|
2.2 Scores on a scale
Standard Deviation 0.92
|
—
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase
Week 12, n=168
|
2.0 Scores on a scale
Standard Deviation 0.87
|
—
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase
Week 13, n=141
|
1.9 Scores on a scale
Standard Deviation 0.85
|
—
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase
Week 14, n=118
|
1.9 Scores on a scale
Standard Deviation 0.69
|
—
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase
Week 15, n=93
|
1.8 Scores on a scale
Standard Deviation 0.71
|
—
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase
Week 16, n=72
|
2.0 Scores on a scale
Standard Deviation 0.89
|
—
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase
Week 17, n=42
|
2.0 Scores on a scale
Standard Deviation 0.70
|
—
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase
Week 18, n=28
|
2.0 Scores on a scale
Standard Deviation 0.88
|
—
|
SECONDARY outcome
Timeframe: Randomization weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32 and 36Population: Randomized ITT Population. Only those par. available at the specified time points were analyzed (represented by n=X). Different par. may have been analyzed at different time points, so the overall number of par. analyzed reflects everyone in the Randomized ITT Population.
Improvement of bipolar illness was based on the CGI-BP(I) score which ranged from 1 (very much improved) to 7 (very much worse). Analysis was performed using mixed model repeated measures.
Outcome measures
| Measure |
Placebo
n=86 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
n=87 Participants
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase
Week 12, n=45, 49
|
3.3 Scores on a scale
Standard Deviation 1.52
|
3.4 Scores on a scale
Standard Deviation 1.29
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase
Week 1, n=84, 85
|
3.3 Scores on a scale
Standard Deviation 1.40
|
3.3 Scores on a scale
Standard Deviation 1.37
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase
Week 2, n=82, 81
|
3.7 Scores on a scale
Standard Deviation 1.48
|
3.6 Scores on a scale
Standard Deviation 1.38
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase
Week 3, n=74, 75
|
3.6 Scores on a scale
Standard Deviation 1.39
|
3.6 Scores on a scale
Standard Deviation 1.34
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase
Week 4, n=65, 70
|
3.6 Scores on a scale
Standard Deviation 1.51
|
3.6 Scores on a scale
Standard Deviation 1.35
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase
Week 6, n=58, 64
|
3.8 Scores on a scale
Standard Deviation 1.64
|
3.4 Scores on a scale
Standard Deviation 1.49
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase
Week 8, n=51, 60
|
3.5 Scores on a scale
Standard Deviation 1.72
|
3.6 Scores on a scale
Standard Deviation 1.47
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase
Week 10, n=45, 55
|
3.3 Scores on a scale
Standard Deviation 1.64
|
3.8 Scores on a scale
Standard Deviation 1.19
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase
Week 16, n=43, 50
|
3.4 Scores on a scale
Standard Deviation 1.73
|
3.5 Scores on a scale
Standard Deviation 1.37
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase
Week 20, n=37, 43
|
3.0 Scores on a scale
Standard Deviation 1.48
|
3.8 Scores on a scale
Standard Deviation 1.36
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase
Week 24, n=34, 36
|
3.0 Scores on a scale
Standard Deviation 1.59
|
3.4 Scores on a scale
Standard Deviation 1.44
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase
Week 28, n=29, 32
|
2.7 Scores on a scale
Standard Deviation 1.56
|
3.5 Scores on a scale
Standard Deviation 1.44
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase
Week 32, n=28, 27
|
3.0 Scores on a scale
Standard Deviation 1.63
|
3.5 Scores on a scale
Standard Deviation 1.28
|
|
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase
Week 36, n=27, 24
|
3.0 Scores on a scale
Standard Deviation 1.68
|
3.6 Scores on a scale
Standard Deviation 1.10
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18Population: Open-Label ITT Population. Only those par. available at the specified time points were analyzed (represented by n=X). Different par. may have been analyzed at different time points, so the overall number of par. analyzed reflects everyone in the Open-Label Population.
The CGI-BP(I) asks the following question: "Compared to the Baseline assessment in this trial, how much has the participant changed?". Scores on the CGI-I range from 1 (very much improved) to 7 (very much worse). The investigator or their designee rated improvement regardless of whether the improvement to be due to drug treatment. Improvement defined as CGI-BP(I)=1 (improved) or 2 (very much improved). Missing data imputed using last-observation carried forward (LOCF).
Outcome measures
| Measure |
Placebo
n=298 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Baseline in the Open-Label Phase
Week 1, n=297
|
27 Participants
|
—
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Baseline in the Open-Label Phase
Week 2, n=297
|
46 Participants
|
—
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Baseline in the Open-Label Phase
Week 3, n=297
|
72 Participants
|
—
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Baseline in the Open-Label Phase
Week 4, n=297
|
86 Participants
|
—
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Baseline in the Open-Label Phase
Week 5, n=297
|
113 Participants
|
—
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Baseline in the Open-Label Phase
Week 6, n=297
|
124 Participants
|
—
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Baseline in the Open-Label Phase
Week 7, n=297
|
138 Participants
|
—
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Baseline in the Open-Label Phase
Week 8, n=297
|
140 Participants
|
—
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Baseline in the Open-Label Phase
Week 9, n=297
|
159 Participants
|
—
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Baseline in the Open-Label Phase
Week 10, n=297
|
176 Participants
|
—
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Baseline in the Open-Label Phase
Week 11, n=297
|
182 Participants
|
—
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Baseline in the Open-Label Phase
Week 12, n=297
|
195 Participants
|
—
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Baseline in the Open-Label Phase
Week 13, n=297
|
205 Participants
|
—
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Baseline in the Open-Label Phase
Week 14, n=297
|
211 Participants
|
—
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Baseline in the Open-Label Phase
Week 15, n=297
|
210 Participants
|
—
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Baseline in the Open-Label Phase
Week 16, n=297
|
209 Participants
|
—
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Baseline in the Open-Label Phase
Week 17, n=297
|
208 Participants
|
—
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Baseline in the Open-Label Phase
Week 18, n=297
|
206 Participants
|
—
|
SECONDARY outcome
Timeframe: Randomization and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, and 36Population: Randomized ITT Population
The CGI-BP(I) asks the following question: "Compared to the Randomization assessment in this trial, how much has the participant changed?". Scores on the CGI-I range from 1 (very much improved) to 7 (very much worse). The investigator or their designee rated improvement regardless of whether the improvement to be due to drug treatment. Improvement defined as CGI-BP(I)=1 (improved) or 2 (very much improved). Missing data imputed using last-observation carried forward (LOCF).
Outcome measures
| Measure |
Placebo
n=86 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
n=87 Participants
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Randomization in the Randomized Phase
Week 1
|
31 Participants
|
31 Participants
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Randomization in the Randomized Phase
Week 2
|
25 Participants
|
22 Participants
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Randomization in the Randomized Phase
Week 3
|
24 Participants
|
21 Participants
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Randomization in the Randomized Phase
Week 4
|
22 Participants
|
19 Participants
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Randomization in the Randomized Phase
Week 6
|
20 Participants
|
23 Participants
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Randomization in the Randomized Phase
Week 8
|
22 Participants
|
19 Participants
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Randomization in the Randomized Phase
Week 10
|
22 Participants
|
12 Participants
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Randomization in the Randomized Phase
Week 12
|
21 Participants
|
17 Participants
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Randomization in the Randomized Phase
Week 16
|
21 Participants
|
16 Participants
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Randomization in the Randomized Phase
Week 20
|
21 Participants
|
14 Participants
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Randomization in the Randomized Phase
Week 24
|
21 Participants
|
15 Participants
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Randomization in the Randomized Phase
Week 28
|
22 Participants
|
15 Participants
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Randomization in the Randomized Phase
Week 32
|
19 Participants
|
15 Participants
|
|
Number of Participants Considered Much Improved or Very Much Improved [Defined as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGI-BP[I]), Score of 1 or 2] at Each Visit Compared to Randomization in the Randomized Phase
Week 36
|
20 Participants
|
13 Participants
|
SECONDARY outcome
Timeframe: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18Population: Open-Label ITT Population
The YMRS consists of 11 items and is based on the participant's report of their mania symptoms. It is clinician rated. Four items (irritability, speech, thought content, and disruptive/aggressive behavior) are rated on a scale of 0 to 8, while the other seven items (elevated mood, increased motor activity-energy, sexual interest, sleep, language, appearance, and insight) are rated on a scale of 0 to 4. The range of scores for the YMRS is 0 (best possible outcome) to 60 (worst possible outcome). The YMRS was completed by the investigator or their qualified designee. Analysis was performed using mixed model repeated measures.
Outcome measures
| Measure |
Placebo
n=298 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase
Week 1
|
-3.2 Scores on a scale
Standard Error 0.39
|
—
|
|
Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase
Week 2
|
-4.8 Scores on a scale
Standard Error 0.42
|
—
|
|
Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase
Week 3
|
-6.4 Scores on a scale
Standard Error 0.45
|
—
|
|
Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase
Week 4
|
-6.5 Scores on a scale
Standard Error 0.46
|
—
|
|
Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase
Week 5
|
-7.5 Scores on a scale
Standard Error 0.50
|
—
|
|
Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase
Week 6
|
-8.4 Scores on a scale
Standard Error 0.50
|
—
|
|
Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase
Week 7
|
-9.1 Scores on a scale
Standard Error 0.51
|
—
|
|
Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase
Week 8
|
-8.8 Scores on a scale
Standard Error 0.48
|
—
|
|
Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase
Week 9
|
-9.6 Scores on a scale
Standard Error 0.48
|
—
|
|
Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase
Week 10
|
-10.3 Scores on a scale
Standard Error 0.49
|
—
|
|
Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase
Week 11
|
-11.1 Scores on a scale
Standard Error 0.48
|
—
|
|
Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase
Week 12
|
-11.6 Scores on a scale
Standard Error 0.53
|
—
|
|
Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase
Week 13
|
-12.0 Scores on a scale
Standard Error 0.58
|
—
|
|
Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase
Week 14
|
-12.0 Scores on a scale
Standard Error 0.59
|
—
|
|
Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase
Week 15
|
-12.4 Scores on a scale
Standard Error 0.63
|
—
|
|
Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase
Week 16
|
-12.3 Scores on a scale
Standard Error 0.78
|
—
|
|
Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase
Week 17
|
-12.2 Scores on a scale
Standard Error 0.88
|
—
|
|
Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase
Week 18
|
-12.1 Scores on a scale
Standard Error 1.43
|
—
|
SECONDARY outcome
Timeframe: Randomization and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, and 36Population: Randomized ITT Population
The YMRS consists of 11 items and is based on the participant's report of their mania symptoms. It is clinician rated. Four items (irritability, speech, thought content, and disruptive/aggressive behavior) are rated on a scale of 0 to 8, while the other seven items (elevated mood, increased motor activity-energy, sexual interest, sleep, language, appearance, and insight) are rated on a scale of 0 to 4. The range of scores for the YMRS is 0 (best possible outcome) to 60 (worst possible outcome). The YMRS was completed by the investigator or their qualified designee. Analysis was performed using mixed model repeated measures.
Outcome measures
| Measure |
Placebo
n=86 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
n=87 Participants
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase
Week 1
|
1.3 Scores on a scale
Standard Error 0.57
|
0.4 Scores on a scale
Standard Error 0.59
|
|
Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase
Week 2
|
2.6 Scores on a scale
Standard Error 0.72
|
2.1 Scores on a scale
Standard Error 0.72
|
|
Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase
Week 3
|
2.6 Scores on a scale
Standard Error 0.69
|
1.3 Scores on a scale
Standard Error 0.71
|
|
Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase
Week 4
|
3.7 Scores on a scale
Standard Error 0.85
|
2.0 Scores on a scale
Standard Error 0.84
|
|
Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase
Week 6
|
4.9 Scores on a scale
Standard Error 0.96
|
2.3 Scores on a scale
Standard Error 0.93
|
|
Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase
Week 8
|
4.3 Scores on a scale
Standard Error 0.98
|
3.5 Scores on a scale
Standard Error 0.93
|
|
Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase
Week 10
|
3.5 Scores on a scale
Standard Error 0.87
|
2.9 Scores on a scale
Standard Error 0.82
|
|
Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase
Week 12
|
3.2 Scores on a scale
Standard Error 0.84
|
1.6 Scores on a scale
Standard Error 0.81
|
|
Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase
Week 16
|
4.7 Scores on a scale
Standard Error 0.93
|
3.0 Scores on a scale
Standard Error 0.89
|
|
Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase
Week 20
|
4.8 Scores on a scale
Standard Error 0.99
|
4.5 Scores on a scale
Standard Error 0.92
|
|
Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase
Week 24
|
4.2 Scores on a scale
Standard Error 1.06
|
2.9 Scores on a scale
Standard Error 1.02
|
|
Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase
Week 28
|
4.4 Scores on a scale
Standard Error 1.04
|
3.7 Scores on a scale
Standard Error 1.01
|
|
Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase
Week 32
|
4.5 Scores on a scale
Standard Error 1.10
|
2.6 Scores on a scale
Standard Error 1.14
|
|
Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase
Week 36
|
3.5 Scores on a scale
Standard Error 0.92
|
1.2 Scores on a scale
Standard Error 0.95
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, and 18Population: Open-Label ITT Population
The P-YMRS was adapted from the YMRS for completion by parents of the pediatric participants with bipolar disorder in order to assess the severity of the manic symptoms. The P-YMRS consisted of 11 items and had a total score range of 0 (best possible outcome) to 60 (worst possible outcome). The P-YMRS was completed by the participant's custodial parent or legal guardian. Analysis was performed using mixed model repeated measures.
Outcome measures
| Measure |
Placebo
n=298 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Change From Baseline in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Open-Label Phase
Week 4
|
-4.7 Scores on a scale
Standard Error 0.57
|
—
|
|
Change From Baseline in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Open-Label Phase
Week 8
|
-6.0 Scores on a scale
Standard Error 0.62
|
—
|
|
Change From Baseline in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Open-Label Phase
Week 12
|
-7.4 Scores on a scale
Standard Error 0.62
|
—
|
|
Change From Baseline in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Open-Label Phase
Week 16
|
-8.2 Scores on a scale
Standard Error 0.72
|
—
|
|
Change From Baseline in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Open-Label Phase
Week 18
|
-9.3 Scores on a scale
Standard Error 1.29
|
—
|
SECONDARY outcome
Timeframe: Randomization and Weeks 8, 16, 24, 32, and 36Population: Randomized ITT Population
The P-YMRS was adapted from the YMRS for completion by parents of the pediatric participants with bipolar disorder in order to assess the severity of the manic symptoms. The P-YMRS consisted of 11 items and had a total score range of 0 (best possible outcome) to 60 (worst possible outcome). The P-YMRS was completed by the participant's custodial parent or legal guardian. Analysis was performed using mixed model repeated measures.
Outcome measures
| Measure |
Placebo
n=86 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
n=87 Participants
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Change From Randomization in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Randomized Phase
Week 24
|
5.3 Scores on a scale
Standard Error 1.35
|
5.7 Scores on a scale
Standard Error 1.29
|
|
Change From Randomization in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Randomized Phase
Week 8
|
4.9 Scores on a scale
Standard Error 0.93
|
4.3 Scores on a scale
Standard Error 0.95
|
|
Change From Randomization in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Randomized Phase
Week 16
|
2.7 Scores on a scale
Standard Error 1.13
|
2.6 Scores on a scale
Standard Error 1.09
|
|
Change From Randomization in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Randomized Phase
Week 32
|
5.1 Scores on a scale
Standard Error 1.33
|
6.0 Scores on a scale
Standard Error 1.32
|
|
Change From Randomization in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Randomized Phase
Week 36
|
5.3 Scores on a scale
Standard Error 1.33
|
4.5 Scores on a scale
Standard Error 1.36
|
SECONDARY outcome
Timeframe: Baseline and Weeks 4, 8, 12, 16, and 18Population: Open-Label ITT Population
The CGI-P is a 10-item scale used to assess attention deficit hyperactivity disorder (ADHD) symptoms in children and adolescents aged 3-17 years of age. The scale is composed of two factors: restless-impulsive behavior and emotional lability. Each item was scored on a 0-3 scale. The range of scores for the CGI-P is 0 (best possible outcome) to 30 (worst possible outcome). The CGI-P was completed by the participant's custodial parent or legal guardian. Analysis was performed using mixed model repeated measures.
Outcome measures
| Measure |
Placebo
n=298 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Change From Baseline in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Open-Label Phase
Week 4
|
-4.0 Scores on a scale
Standard Error 0.36
|
—
|
|
Change From Baseline in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Open-Label Phase
Week 8
|
-5.7 Scores on a scale
Standard Error 0.43
|
—
|
|
Change From Baseline in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Open-Label Phase
Week 12
|
-6.7 Scores on a scale
Standard Error 0.47
|
—
|
|
Change From Baseline in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Open-Label Phase
Week 16
|
-7.1 Scores on a scale
Standard Error 0.56
|
—
|
|
Change From Baseline in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Open-Label Phase
Week 18
|
-8.2 Scores on a scale
Standard Error 1.07
|
—
|
SECONDARY outcome
Timeframe: Randomization and Weeks 8, 16, 24, 32, and 36Population: Randomized ITT Population
The CGI-P is a 10-item scale used to assess attention deficit hyperactivity disorder (ADHD) symptoms in children and adolescents aged 3-17 years of age. The scale is composed of two factors: restless-impulsive behavior and emotional lability. Each item was scored on a 0-3 scale. The range of scores for the CGI-P is 0 (best possible outcome) to 30 (worst possible outcome). The CGI-P was completed by the participant's custodial parent or legal guardian. Analysis was performed using mixed model repeated measures.
Outcome measures
| Measure |
Placebo
n=86 Participants
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
Lamotrigine
n=87 Participants
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks.
|
|---|---|---|
|
Change From Randomization in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Randomized Phase.
Week 24
|
2.4 Scores on a scale
Standard Error 1.12
|
3.1 Scores on a scale
Standard Error 1.05
|
|
Change From Randomization in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Randomized Phase.
Week 32
|
2.7 Scores on a scale
Standard Error 1.10
|
2.6 Scores on a scale
Standard Error 1.08
|
|
Change From Randomization in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Randomized Phase.
Week 36
|
1.5 Scores on a scale
Standard Error 1.00
|
0.5 Scores on a scale
Standard Error 1.03
|
|
Change From Randomization in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Randomized Phase.
Week 8
|
3.1 Scores on a scale
Standard Error 0.75
|
2.1 Scores on a scale
Standard Error 0.77
|
|
Change From Randomization in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Randomized Phase.
Week 16
|
3.4 Scores on a scale
Standard Error 0.92
|
1.2 Scores on a scale
Standard Error 0.90
|
Adverse Events
Open-Label and Open-Label Taper Phases: LTG
Serious events: 19 serious events
Other events: 177 other events
Deaths: 0 deaths
Randomized and Double-blind Taper Phases: Placebo
Serious events: 5 serious events
Other events: 41 other events
Deaths: 0 deaths
Randomized and Double-blind Taper Phases: LTG
Serious events: 1 serious events
Other events: 45 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Open-Label and Open-Label Taper Phases: LTG
n=298 participants at risk
Participants (par.) received lamotrigine (LTG) up to a maximum dose depending on their age and concomitant bipolar medication group. Participants 10 -12 years of age received LTG up to a maximum dose of : 3 milligrams/kilograms (mg/kg)/day or 100 mg/day, whichever was less; or 6 mg/kg/day or 200 mg/day whichever was less; or 12 mg/kg/day or 300 mg/day whichever was less, depending on their bipolar medication group. Participants 13-17 years of age received LTG up to a maximum dose of 150 mg/day, 300 mg/day, or 400 mg/day depending on their bipolar medication group. Participants took LTG for a duration of up to 18 weeks. Participants discontinuing from the study during the Open-Label Phase entered an open Taper and Follow-up Phase.The Taper and Follow-up Phase may last up to 4 weeks, dependent on the dose of LTG the participant received during the Open-Label Phase.
|
Randomized and Double-blind Taper Phases: Placebo
n=86 participants at risk
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. Participants completing the Randomized Phase entered Double-Blind Taper and Follow-up Phase. The Taper and Follow-up Phase may last up to 4 weeks. The participant received Placebo during this Phase.
|
Randomized and Double-blind Taper Phases: LTG
n=87 participants at risk
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. Participants completing the Randomized Phase entered Double-Blind Taper and Follow-up Phase. The Taper and Follow-up Phase may last up to 4 weeks, dependent on the dose of LTG the participant received during the Randomized Phase.
|
|---|---|---|---|
|
Psychiatric disorders
Suicidal ideation
|
1.7%
5/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
1.2%
1/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Psychiatric disorders
Agitation
|
1.0%
3/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Psychiatric disorders
Mania
|
1.0%
3/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
1.2%
1/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Psychiatric disorders
Aggression
|
0.34%
1/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Psychiatric disorders
Anxiety
|
0.34%
1/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Psychiatric disorders
Bipolar I disorder
|
0.34%
1/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
1.2%
1/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Psychiatric disorders
Bipolar disorder
|
0.34%
1/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Psychiatric disorders
Impulsive behaviour
|
0.34%
1/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Psychiatric disorders
Intentional self-injury
|
0.34%
1/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Psychiatric disorders
Pressure of speech
|
0.34%
1/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Psychiatric disorders
Emotional disorder
|
0.00%
0/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
1.1%
1/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
General disorders
Irritability
|
0.67%
2/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasm
|
0.34%
1/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.34%
1/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.34%
1/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Infections and infestations
Infectious mononucleosis
|
0.00%
0/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
1.2%
1/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
1.2%
1/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Injury, poisoning and procedural complications
Intentional overdose
|
0.00%
0/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
1.2%
1/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
Other adverse events
| Measure |
Open-Label and Open-Label Taper Phases: LTG
n=298 participants at risk
Participants (par.) received lamotrigine (LTG) up to a maximum dose depending on their age and concomitant bipolar medication group. Participants 10 -12 years of age received LTG up to a maximum dose of : 3 milligrams/kilograms (mg/kg)/day or 100 mg/day, whichever was less; or 6 mg/kg/day or 200 mg/day whichever was less; or 12 mg/kg/day or 300 mg/day whichever was less, depending on their bipolar medication group. Participants 13-17 years of age received LTG up to a maximum dose of 150 mg/day, 300 mg/day, or 400 mg/day depending on their bipolar medication group. Participants took LTG for a duration of up to 18 weeks. Participants discontinuing from the study during the Open-Label Phase entered an open Taper and Follow-up Phase.The Taper and Follow-up Phase may last up to 4 weeks, dependent on the dose of LTG the participant received during the Open-Label Phase.
|
Randomized and Double-blind Taper Phases: Placebo
n=86 participants at risk
Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. Participants completing the Randomized Phase entered Double-Blind Taper and Follow-up Phase. The Taper and Follow-up Phase may last up to 4 weeks. The participant received Placebo during this Phase.
|
Randomized and Double-blind Taper Phases: LTG
n=87 participants at risk
Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. Participants completing the Randomized Phase entered Double-Blind Taper and Follow-up Phase. The Taper and Follow-up Phase may last up to 4 weeks, dependent on the dose of LTG the participant received during the Randomized Phase.
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
35.6%
106/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
20.9%
18/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
20.7%
18/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Nervous system disorders
Dizziness
|
8.1%
24/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
15.8%
47/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
3.5%
3/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
5.7%
5/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Gastrointestinal disorders
Nausea
|
13.1%
39/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Gastrointestinal disorders
Diarrhoea
|
7.7%
23/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Gastrointestinal disorders
Vomiting
|
8.4%
25/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
3.5%
3/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
5.7%
5/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Infections and infestations
Nasopharyngitis
|
8.4%
25/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
5.8%
5/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
8.0%
7/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Infections and infestations
Influenza
|
0.00%
0/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
2.3%
2/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
8.0%
7/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
7.0%
21/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
4.7%
4/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
8.0%
7/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
10.1%
30/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
2.3%
2/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
8.0%
7/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
0.00%
0/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
7.0%
6/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
6.9%
6/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Psychiatric disorders
Insomnia
|
7.7%
23/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
5.8%
5/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
6.9%
6/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Psychiatric disorders
Suicidal ideation
|
5.4%
16/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
Psychiatric disorders
Agitation
|
0.00%
0/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
1.2%
1/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
5.7%
5/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
General disorders
Irritability
|
5.4%
16/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
16.3%
14/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
8.0%
7/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
General disorders
Fatigue
|
5.7%
17/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
0.00%
0/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
|
General disorders
Pyrexia
|
0.00%
0/298 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
5.8%
5/86 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
2.3%
2/87 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4).
On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product.
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER