Bipolar Disorder
Conditions
Keywords
Bipolar I pediatric lamictal adolescent
Brief summary
The study will be a multi-center, parallel, group, placebo control, double-blind, randomized controlled trial of lamictal as add-on maintenance treatment in pediatric outpatients (aged 10 to 17 years) diagnosed with Bipolar I disorder. The study consists of 4 phases: Screen (approximately 2 weeks), Open label phase (up to 18 weeks), Randomized phase (up to 36 weeks) and Taper and follow-up phase (up to 4 weeks).
Interventions
DRUGlamictal
Flexible Dosing
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Subject is male or female between the ages of 10 and 17 years, inclusive. * Subject has a diagnosis of bipolar I disorder and is currently experiencing a manic/hypomanic, depressed, or mixed mood episode * Subject is currently receiving a stable treatment regimen. * Subject is living with his/her custodial parent(s) or legal guardian(s) and has contact with them on a daily basis.
Exclusion criteria
* Subject has been diagnosed with a primary Axis I disorder (with the exception of bipolar I disorder, ADHD, anxiety disorders, oppositional defiant disorder, or conduct disorder) or any Axis II disorder. * Subject currently has signs or symptoms of psychosis or a history of psychosis within the previous four weeks. * Subject has been diagnosed with epilepsy, autism, Asperger's syndrome, or Tourette's syndrome. * Subject has experienced a serious rash, such as Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis, or a rash otherwise requiring hospitalization. * Subject has experienced a rash related to prior LAMICTAL use, or for whom LAMICTAL treatment was discontinued for clinically significant safety reasons. * Subject has received any antidepressant medication, or atomoxetine, during the four weeks prior to the Screen Visit. * Subject has initiated psychotherapy within 2 months prior to the Screen Visit, or plans to initiate psychotherapy during the trial. * Subject in the 10-12 year old age group has a Body Mass Index (BMI) less than or equal 15 or greater than or equal to 30; a subject in the 13-17 year old age group has a BMI less than or equal to 17 or greater than or equal to 34. * Subject tests positive for illicit drug use at the Screen Visit, has a history of alcohol or substance abuse or dependence (other than nicotine dependence) within the past three months, or has a positive blood alcohol level at the Screen Visit. * Subject, in the investigator's judgment, poses a current homicidal or serious suicidal risk, has made a suicide attempt within the twelve months preceding the Screen Visit, has ever been homicidal.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time From Randomization to the Occurrence of a Bipolar Event (TOBE) | From randomization until Week 36 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time From Randomization to Intervention for a Mood Episode (TIME) | From randomization until intervention administered for a mood episode (up to Week 36) | 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). |
| Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix) | From randomization until intervention administered for depression, mania/hypomania or a mixed episode (up to Week 36) | 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). |
| Number of Participants Experiencing a Relapse/Recurrence to Depression, Mania/Hypomania, or Mixed Mood State | From randomization until a relapse/recurrence to depression, mania/hypomania, or mixed mood state (up to Week 36) | 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. |
| Number of Participants Experiencing a Relapse/Recurrence Within the First 30, 90, and 180 Days in the Randomized Phase | From randomization up to Week 36 | 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. |
| 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 | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18 | 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. |
| 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 | Randomization and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, and 36 | 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. |
| 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 | Baseline and Weeks 4, 8, 12, 16, and 18 | 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. |
| Change From Randomization in the Quick Inventory of Depressive Symptomatology - Self-report Adolescent Version (QIDS-A17-SR) at Each Visit in the Randomized Phase | Randomization and Weeks 8, 16, 24, 32, and 36 | 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. |
| Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18 | 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. |
| Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase | Randomization and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, and 36 | 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. |
| Time From Randomization to Withdrawal From the Study for Any Cause (TTW) | From randomization until withdrawal from the study for any cause (up to Week 36) | 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). |
| Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase | Randomization weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32 and 36 | 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. |
| 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 | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18 | 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). |
| 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 | Randomization and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, and 36 | 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). |
| Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase | Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18 | 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. |
| Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase | Randomization and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, and 36 | 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. |
| Change From Baseline in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Open-Label Phase | Baseline and Weeks 4, 8, 12, 16, and 18 | 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. |
| Change From Randomization in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Randomized Phase | Randomization and Weeks 8, 16, 24, 32, and 36 | 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. |
| Change From Baseline in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Open-Label Phase | Baseline and Weeks 4, 8, 12, 16, and 18 | 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. |
| Change From Randomization in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Randomized Phase. | Randomization and Weeks 8, 16, 24, 32, and 36 | 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. |
| Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase | Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18 | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 86 |
| 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. | 87 |
| Total | 173 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Open-Label Phase | Adverse Event | 26 | 0 | 0 |
| Open-Label Phase | Lack of Efficacy | 18 | 0 | 0 |
| Open-Label Phase | Lost to Follow-up | 7 | 0 | 0 |
| Open-Label Phase | Physician Decision | 2 | 0 | 0 |
| Open-Label Phase | Protocol Violation | 35 | 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 | Lost to Follow-up | 0 | 2 | 3 |
| Randomized Phase | Physician Decision | 0 | 3 | 1 |
| Randomized Phase | Protocol Violation | 0 | 9 | 13 |
| Randomized Phase | Withdrawal by Subject | 0 | 14 | 22 |
Baseline characteristics
| Characteristic | Lamotrigine | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 13.4 Years STANDARD_DEVIATION 2.33 | 13.5 Years STANDARD_DEVIATION 2.22 | 13.5 Years STANDARD_DEVIATION 2.27 |
| Gender Female | 33 Participants | 39 Participants | 72 Participants |
| Gender Male | 54 Participants | 47 Participants | 101 Participants |
| Race/Ethnicity, Customized African American/African Heritage | 9 Participants | 9 Participants | 18 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Mixed Race | 6 Participants | 4 Participants | 10 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 71 Participants | 71 Participants | 142 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 177 / 298 | 41 / 86 | 45 / 87 |
| serious Total, serious adverse events | 19 / 298 | 5 / 86 | 1 / 87 |
Outcome results
Primary
Time From Randomization to the Occurrence of a Bipolar Event (TOBE)
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).
Time frame: From randomization until Week 36
Population: Randomized Intent-to-Treat (ITT) Population: all participants who were randomized to LTG or placebo and received at least one dose of investigational product.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Time From Randomization to the Occurrence of a Bipolar Event (TOBE) | Stratum: Depression, n=22,21 | 50 Days | Standard Error 3.8 |
| Placebo | Time From Randomization to the Occurrence of a Bipolar Event (TOBE) | Stratum: Mania/Hypomania, n=36, 37 | 120 Days | Standard Error 12.2 |
| Placebo | Time From Randomization to the Occurrence of a Bipolar Event (TOBE) | Stratum: Mixed Mood, n=28, 29 | 107 Days | Standard Error 13.8 |
| Lamotrigine | Time From Randomization to the Occurrence of a Bipolar Event (TOBE) | Stratum: Depression, n=22,21 | 155 Days | Standard Error 14.7 |
| Lamotrigine | Time From Randomization to the Occurrence of a Bipolar Event (TOBE) | Stratum: Mania/Hypomania, n=36, 37 | 163 Days | Standard Error 12.2 |
| Lamotrigine | Time From Randomization to the Occurrence of a Bipolar Event (TOBE) | Stratum: Mixed Mood, n=28, 29 | 136 Days | Standard Error 15.4 |
p-value: 0.0717Log Rank
Secondary
Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase
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.
Time frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18
Population: Open-Label ITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 0.1 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
Secondary
Change From Baseline in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Open-Label Phase
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.
Time frame: Baseline and Weeks 4, 8, 12, 16, and 18
Population: Open-Label ITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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
Change From Baseline in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Open-Label Phase
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.
Time frame: Baseline and Weeks 4, 8, 12, 16, and 18
Population: Open-Label ITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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
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
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.
Time frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18
Population: Open-Label ITT population: all participants who entered the Open-Label Phase and received at least one dose of LTG.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 0.3 |
| Placebo | 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 0.3 |
| Placebo | 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 |
| Placebo | 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 0.3 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 0.4 |
| Placebo | 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 |
| Placebo | 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 0.3 |
| Placebo | 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 0.3 |
| Placebo | 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 |
| Placebo | 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 0.3 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 0.7 |
Secondary
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
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.
Time frame: Baseline and Weeks 4, 8, 12, 16, and 18
Population: Open-Label ITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
Secondary
Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase
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.
Time frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18
Population: Open-Label ITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 0.5 |
| Placebo | 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 0.5 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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
Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase
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.
Time frame: Randomization and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, and 36
Population: Randomized ITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Lamotrigine | Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase | Week 8 | 0.4 Scores on a scale | Standard Error 0.14 |
| Lamotrigine | Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase | Week 12 | 0.4 Scores on a scale | Standard Error 0.14 |
| Lamotrigine | Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase | Week 28 | 0.5 Scores on a scale | Standard Error 0.16 |
| Lamotrigine | Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase | Week 36 | 0.3 Scores on a scale | Standard Error 0.21 |
| Lamotrigine | Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase | Week 1 | 0.0 Scores on a scale | Standard Error 0.09 |
| Lamotrigine | Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase | Week 10 | 0.6 Scores on a scale | Standard Error 0.13 |
| Lamotrigine | Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase | Week 2 | 0.2 Scores on a scale | Standard Error 0.12 |
| Lamotrigine | Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase | Week 24 | 0.6 Scores on a scale | Standard Error 0.16 |
| Lamotrigine | Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase | Week 3 | 0.2 Scores on a scale | Standard Error 0.12 |
| Lamotrigine | 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 0.15 |
| Lamotrigine | Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase | Week 4 | 0.3 Scores on a scale | Standard Error 0.13 |
| Lamotrigine | Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase | Week 32 | 0.5 Scores on a scale | Standard Error 0.2 |
| Lamotrigine | Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase | Week 6 | 0.4 Scores on a scale | Standard Error 0.15 |
| Lamotrigine | Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase | Week 20 | 0.8 Scores on a scale | Standard Error 0.16 |
Secondary
Change From Randomization in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Randomized Phase.
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.
Time frame: Randomization and Weeks 8, 16, 24, 32, and 36
Population: Randomized ITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 1.1 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Lamotrigine | Change From Randomization in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Randomized Phase. | Week 36 | 0.5 Scores on a scale | Standard Error 1.03 |
| Lamotrigine | Change From Randomization in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Randomized Phase. | Week 24 | 3.1 Scores on a scale | Standard Error 1.05 |
| Lamotrigine | Change From Randomization in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Randomized Phase. | Week 32 | 2.6 Scores on a scale | Standard Error 1.08 |
| Lamotrigine | Change From Randomization in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Randomized Phase. | Week 8 | 2.1 Scores on a scale | Standard Error 0.77 |
| Lamotrigine | Change From Randomization in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Randomized Phase. | Week 16 | 1.2 Scores on a scale | Standard Error 0.9 |
Secondary
Change From Randomization in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Randomized Phase
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.
Time frame: Randomization and Weeks 8, 16, 24, 32, and 36
Population: Randomized ITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Lamotrigine | Change From Randomization in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Randomized Phase | Week 36 | 4.5 Scores on a scale | Standard Error 1.36 |
| Lamotrigine | Change From Randomization in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Randomized Phase | Week 16 | 2.6 Scores on a scale | Standard Error 1.09 |
| Lamotrigine | Change From Randomization in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Randomized Phase | Week 24 | 5.7 Scores on a scale | Standard Error 1.29 |
| Lamotrigine | Change From Randomization in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Randomized Phase | Week 32 | 6.0 Scores on a scale | Standard Error 1.32 |
| Lamotrigine | Change From Randomization in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Randomized Phase | Week 8 | 4.3 Scores on a scale | Standard Error 0.95 |
Secondary
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
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.
Time frame: Randomization and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, and 36
Population: Randomized ITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 0.3 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 0.4 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 0.5 |
| Placebo | 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 |
| Placebo | 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 |
| Lamotrigine | 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 | 2.3 Scores on a scale | Standard Error 0.57 |
| Lamotrigine | 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 | 1.1 Scores on a scale | Standard Error 0.37 |
| Lamotrigine | 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 | 1.0 Scores on a scale | Standard Error 0.39 |
| Lamotrigine | 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 | 1.7 Scores on a scale | Standard Error 0.45 |
| Lamotrigine | 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 | 2.5 Scores on a scale | Standard Error 0.46 |
| Lamotrigine | 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 | 1.8 Scores on a scale | Standard Error 0.51 |
| Lamotrigine | 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 | 0.5 Scores on a scale | Standard Error 0.31 |
| Lamotrigine | 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 | 1.9 Scores on a scale | Standard Error 0.63 |
| Lamotrigine | 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 | 0.6 Scores on a scale | Standard Error 0.36 |
| Lamotrigine | 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 | 1.5 Scores on a scale | Standard Error 0.47 |
| Lamotrigine | 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 | 1.5 Scores on a scale | Standard Error 0.41 |
| Lamotrigine | 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 | 1.2 Scores on a scale | Standard Error 0.39 |
| Lamotrigine | 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 | 1.8 Scores on a scale | Standard Error 0.47 |
| Lamotrigine | 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 | 1.9 Scores on a scale | Standard Error 0.72 |
Secondary
Change From Randomization in the Quick Inventory of Depressive Symptomatology - Self-report Adolescent Version (QIDS-A17-SR) at Each Visit in the Randomized Phase
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.
Time frame: Randomization and Weeks 8, 16, 24, 32, and 36
Population: Randomized ITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 0.6 |
| Placebo | 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 0.6 |
| Placebo | 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 |
| Lamotrigine | 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 | 0.2 Scores on a scale | Standard Error 0.63 |
| Lamotrigine | 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 | 1.5 Scores on a scale | Standard Error 0.56 |
| Lamotrigine | 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 | 1.2 Scores on a scale | Standard Error 0.48 |
| Lamotrigine | 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 | 0.8 Scores on a scale | Standard Error 0.68 |
| Lamotrigine | 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 | 1.4 Scores on a scale | Standard Error 0.58 |
Secondary
Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase
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.
Time frame: Randomization and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, and 36
Population: Randomized ITT Population
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 1.1 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Lamotrigine | Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase | Week 16 | 3.0 Scores on a scale | Standard Error 0.89 |
| Lamotrigine | Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase | Week 2 | 2.1 Scores on a scale | Standard Error 0.72 |
| Lamotrigine | Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase | Week 6 | 2.3 Scores on a scale | Standard Error 0.93 |
| Lamotrigine | Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase | Week 3 | 1.3 Scores on a scale | Standard Error 0.71 |
| Lamotrigine | Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase | Week 24 | 2.9 Scores on a scale | Standard Error 1.02 |
| Lamotrigine | Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase | Week 12 | 1.6 Scores on a scale | Standard Error 0.81 |
| Lamotrigine | Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase | Week 8 | 3.5 Scores on a scale | Standard Error 0.93 |
| Lamotrigine | Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase | Week 28 | 3.7 Scores on a scale | Standard Error 1.01 |
| Lamotrigine | Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase | Week 10 | 2.9 Scores on a scale | Standard Error 0.82 |
| Lamotrigine | Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase | Week 32 | 2.6 Scores on a scale | Standard Error 1.14 |
| Lamotrigine | Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase | Week 20 | 4.5 Scores on a scale | Standard Error 0.92 |
| Lamotrigine | Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase | Week 1 | 0.4 Scores on a scale | Standard Error 0.59 |
| Lamotrigine | Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase | Week 36 | 1.2 Scores on a scale | Standard Error 0.95 |
| Lamotrigine | Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase | Week 4 | 2.0 Scores on a scale | Standard Error 0.84 |
Secondary
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
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).
Time frame: Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18
Population: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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
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
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).
Time frame: Randomization and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, and 36
Population: Randomized ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Lamotrigine | 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 | 13 Participants |
| Lamotrigine | 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 | 12 Participants |
| Lamotrigine | 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 | 15 Participants |
| Lamotrigine | 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 |
| Lamotrigine | 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 | 22 Participants |
| Lamotrigine | 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 | 21 Participants |
| Lamotrigine | 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 | 19 Participants |
| Lamotrigine | 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 | 19 Participants |
| Lamotrigine | 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 | 17 Participants |
| Lamotrigine | 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 | 16 Participants |
| Lamotrigine | 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 | 14 Participants |
| Lamotrigine | 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 | 15 Participants |
| Lamotrigine | 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 | 15 Participants |
| Lamotrigine | 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 | 23 Participants |
Secondary
Number of Participants Experiencing a Relapse/Recurrence to Depression, Mania/Hypomania, or Mixed Mood State
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.
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Number of Participants Experiencing a Relapse/Recurrence to Depression, Mania/Hypomania, or Mixed Mood State | Depression | 5 Participants |
| Placebo | Number of Participants Experiencing a Relapse/Recurrence to Depression, Mania/Hypomania, or Mixed Mood State | Mania/hypomania | 16 Participants |
| Placebo | Number of Participants Experiencing a Relapse/Recurrence to Depression, Mania/Hypomania, or Mixed Mood State | Mixed episode state | 10 Participants |
| Lamotrigine | Number of Participants Experiencing a Relapse/Recurrence to Depression, Mania/Hypomania, or Mixed Mood State | Depression | 3 Participants |
| Lamotrigine | Number of Participants Experiencing a Relapse/Recurrence to Depression, Mania/Hypomania, or Mixed Mood State | Mania/hypomania | 6 Participants |
| Lamotrigine | Number of Participants Experiencing a Relapse/Recurrence to Depression, Mania/Hypomania, or Mixed Mood State | Mixed episode state | 9 Participants |
Secondary
Number of Participants Experiencing a Relapse/Recurrence Within the First 30, 90, and 180 Days in the Randomized Phase
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.
Time frame: From randomization 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Lamotrigine | 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 | 3 Participants |
| Lamotrigine | 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 | 4 Participants |
| Lamotrigine | 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 | 5 Participants |
| Lamotrigine | 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 |
| Lamotrigine | 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 | 2 Participants |
| Lamotrigine | 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 | 6 Participants |
| Lamotrigine | 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 | 8 Participants |
| Lamotrigine | 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 | 2 Participants |
| Lamotrigine | 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 | 2 Participants |
Secondary
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase
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.
Time frame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 0.8 |
| Placebo | 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 0.9 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 0.7 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
Secondary
Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase
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.
Time frame: Randomization weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32 and 36
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 1.4 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Lamotrigine | Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase | Week 36, n=27, 24 | 3.6 Scores on a scale | Standard Deviation 1.1 |
| Lamotrigine | Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase | Week 6, n=58, 64 | 3.4 Scores on a scale | Standard Deviation 1.49 |
| Lamotrigine | Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase | Week 32, n=28, 27 | 3.5 Scores on a scale | Standard Deviation 1.28 |
| Lamotrigine | 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 1.37 |
| Lamotrigine | Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase | Week 2, n=82, 81 | 3.6 Scores on a scale | Standard Deviation 1.38 |
| Lamotrigine | 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 1.34 |
| Lamotrigine | Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase | Week 8, n=51, 60 | 3.6 Scores on a scale | Standard Deviation 1.47 |
| Lamotrigine | Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase | Week 10, n=45, 55 | 3.8 Scores on a scale | Standard Deviation 1.19 |
| Lamotrigine | Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase | Week 12, n=45, 49 | 3.4 Scores on a scale | Standard Deviation 1.29 |
| Lamotrigine | Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase | Week 16, n=43, 50 | 3.5 Scores on a scale | Standard Deviation 1.37 |
| Lamotrigine | Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase | Week 20, n=37, 43 | 3.8 Scores on a scale | Standard Deviation 1.36 |
| Lamotrigine | Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase | Week 24, n=34, 36 | 3.4 Scores on a scale | Standard Deviation 1.44 |
| Lamotrigine | Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase | Week 28, n=29, 32 | 3.5 Scores on a scale | Standard Deviation 1.44 |
| Lamotrigine | 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 1.35 |
Secondary
Time From Randomization to Intervention for a Mood Episode (TIME)
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).
Time frame: From randomization until intervention administered for a mood episode (up to Week 36)
Population: Randomized ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Time From Randomization to Intervention for a Mood Episode (TIME) | Stratum: Depression, n=22, 21 | 62 Days | Standard Error 5.2 |
| Placebo | Time From Randomization to Intervention for a Mood Episode (TIME) | Stratum: Mania/Hypomania, n=36, 37 | 129 Days | Standard Error 11.7 |
| Placebo | Time From Randomization to Intervention for a Mood Episode (TIME) | Stratum: Mixed Mood, n=28, 29 | 120 Days | Standard Error 13.7 |
| Lamotrigine | Time From Randomization to Intervention for a Mood Episode (TIME) | Stratum: Depression, n=22, 21 | 164 Days | Standard Error 12.7 |
| Lamotrigine | Time From Randomization to Intervention for a Mood Episode (TIME) | Stratum: Mania/Hypomania, n=36, 37 | 179 Days | Standard Error 10.8 |
| Lamotrigine | Time From Randomization to Intervention for a Mood Episode (TIME) | Stratum: Mixed Mood, n=28, 29 | 127 Days | Standard Error 12 |
Secondary
Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix)
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).
Time frame: From randomization until intervention administered for depression, mania/hypomania or a mixed episode (up to Week 36)
Population: Randomized ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix) | TIDep: Mania/Hypomania, n=36, 37 | NA Days | — |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Placebo | 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 |
| Lamotrigine | Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix) | TIMix: Mania/Hypomania, n=36, 37 | 194 Days | Standard Error 7.5 |
| Lamotrigine | Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix) | TIDep: Mania/Hypomania, n=36, 37 | NA Days | — |
| Lamotrigine | Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix) | TIMan: Depression, n=22, 21 | 182 Days | — |
| Lamotrigine | Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix) | TIMix: Depression, n=22, 21 | 158 Days | — |
| Lamotrigine | Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix) | TIMan: Mania/Hypomania, n=36, 37 | 61 Days | Standard Error 2.1 |
| Lamotrigine | Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix) | TIMan: Mixed Mood, n=28, 29 | 148 Days | Standard Error 8.5 |
| Lamotrigine | Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix) | TIMix: Mixed Mood, n=28, 29 | 57 Days | Standard Error 2.5 |
| Lamotrigine | Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix) | TIDep: Mixed Mood, n=28, 29 | 159 Days | — |
| Lamotrigine | Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix) | TIDep: Depression, n=22, 21 | 46 Days | Standard Error 1.5 |
Secondary
Time From Randomization to Withdrawal From the Study for Any Cause (TTW)
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).
Time frame: From randomization until withdrawal from the study for any cause (up to Week 36)
Population: Randomized ITT Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Time From Randomization to Withdrawal From the Study for Any Cause (TTW) | Stratum: Mania/Hypomania, n=36, 37 | 138 Days | Standard Error 17.3 |
| Placebo | Time From Randomization to Withdrawal From the Study for Any Cause (TTW) | Stratum: Mixed Mood, n=28, 29 | 101 Days | Standard Error 15.7 |
| Placebo | Time From Randomization to Withdrawal From the Study for Any Cause (TTW) | Stratum: Depression, n=22, 21 | 113 Days | Standard Error 21.4 |
| Lamotrigine | Time From Randomization to Withdrawal From the Study for Any Cause (TTW) | Stratum: Mania/Hypomania, n=36, 37 | 144 Days | Standard Error 15.6 |
| Lamotrigine | Time From Randomization to Withdrawal From the Study for Any Cause (TTW) | Stratum: Mixed Mood, n=28, 29 | 106 Days | Standard Error 16.3 |
| Lamotrigine | Time From Randomization to Withdrawal From the Study for Any Cause (TTW) | Stratum: Depression, n=22, 21 | 141 Days | Standard Error 20 |