Lamictal as Add-on Treatment for Bipolar I Disorder in Pediatric Patients
Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT00723450
Collaborator
(none)
301
46
2
61
6.5
0.1
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
301 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
The Evaluation of Lamictal as an Add-on Treatment for Bipolar I Disorder in Children and Adolescents, 10 to 17 Years of Age
Study Start Date
:
Jul 1, 2008
Actual Primary Completion Date
:
Aug 1, 2013
Actual Study Completion Date
:
Aug 1, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: placebo Placebo Controlled |
Drug: lamictal
Flexible Dosing
|
| Experimental: lamictal Flexible Dosing |
Drug: lamictal
Flexible Dosing
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome 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).
- 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.
- 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.
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
10 Years
to 17 Years
Sexes Eligible for Study:
All
Accepts 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | GSK Investigational Site | Dothan | Alabama | United States | 36305 |
| 2 | GSK Investigational Site | Scottsdale | Arizona | United States | 85252 |
| 3 | GSK Investigational Site | San Diego | California | United States | 92108 |
| 4 | GSK Investigational Site | Stanford | California | United States | 94304 |
| 5 | GSK Investigational Site | Washington | District of Columbia | United States | 20010 |
| 6 | GSK Investigational Site | Bradenton | Florida | United States | 34201 |
| 7 | GSK Investigational Site | Gainesville | Florida | United States | 32607 |
| 8 | GSK Investigational Site | Jacksonville | Florida | United States | 32216 |
| 9 | GSK Investigational Site | Orlando | Florida | United States | 32839 |
| 10 | GSK Investigational Site | Tampa | Florida | United States | 33613 |
| 11 | GSK Investigational Site | Winter Park | Florida | United States | 32789 |
| 12 | GSK Investigational Site | Smyrna | Georgia | United States | 30080 |
| 13 | GSK Investigational Site | Libertyville | Illinois | United States | 60048 |
| 14 | GSK Investigational Site | Naperville | Illinois | United States | 60563 |
| 15 | GSK Investigational Site | Indianapolis | Indiana | United States | 46202 |
| 16 | GSK Investigational Site | Overland Park | Kansas | United States | 66211 |
| 17 | GSK Investigational Site | Wichita | Kansas | United States | 67206 |
| 18 | GSK Investigational Site | Shreveport | Louisiana | United States | 71103 |
| 19 | GSK Investigational Site | Baltimore | Maryland | United States | 21208 |
| 20 | GSK Investigational Site | Boston | Massachusetts | United States | 02114 |
| 21 | GSK Investigational Site | Boston | Massachusetts | United States | 02115 |
| 22 | GSK Investigational Site | Springfield | Massachusetts | United States | 01199 |
| 23 | GSK Investigational Site | Worcester | Massachusetts | United States | 01655 |
| 24 | GSK Investigational Site | Rochester | Minnesota | United States | 55905 |
| 25 | GSK Investigational Site | St. Charles | Missouri | United States | 63304 |
| 26 | GSK Investigational Site | Lincoln | Nebraska | United States | 68526 |
| 27 | GSK Investigational Site | Piscataway | New Jersey | United States | 08854 |
| 28 | GSK Investigational Site | Albuquerque | New Mexico | United States | 87109 |
| 29 | GSK Investigational Site | Mount Kisco | New York | United States | 10549 |
| 30 | GSK Investigational Site | Stony Brook | New York | United States | 11794-8790 |
| 31 | GSK Investigational Site | Chapel Hill | North Carolina | United States | 27517 |
| 32 | GSK Investigational Site | Fargo | North Dakota | United States | 58104 |
| 33 | GSK Investigational Site | Cincinnati | Ohio | United States | 45219 |
| 34 | GSK Investigational Site | Cincinnati | Ohio | United States | 45229 |
| 35 | GSK Investigational Site | Cleveland | Ohio | United States | 44106 |
| 36 | GSK Investigational Site | Columbus | Ohio | United States | 43210 |
| 37 | GSK Investigational Site | Toledo | Ohio | United States | 43609 |
| 38 | GSK Investigational Site | Philadelphia | Pennsylvania | United States | 19104 |
| 39 | GSK Investigational Site | Dallas | Texas | United States | 75235 |
| 40 | GSK Investigational Site | Houston | Texas | United States | 77007 |
| 41 | GSK Investigational Site | Houston | Texas | United States | 77008 |
| 42 | GSK Investigational Site | Houston | Texas | United States | 77030 |
| 43 | GSK Investigational Site | Salt Lake City | Utah | United States | 84105 |
| 44 | GSK Investigational Site | Roanoke | Virginia | United States | 24013 |
| 45 | GSK Investigational Site | Kirkland | Washington | United States | 98033 |
| 46 | GSK Investigational Site | Seattle | Washington | United States | 98105 |
Sponsors and Collaborators
- GlaxoSmithKline
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00723450
Other Study ID Numbers:
- SCA102833
First Posted:
Jul 28, 2008
Last Update Posted:
Jan 9, 2017
Last Verified:
Nov 1, 2016
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by GlaxoSmithKline
Additional relevant MeSH terms:
Study Results
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 Detail | 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. |
| Arm/Group Title | LTG: Open-Label Phase | Placebo | Lamotrigine |
|---|---|---|---|
| Arm/Group Description | Participants (par.) received lamotrigine (LTG) up to a maximum dose depending on their age and concomitant bipolar medication group. Participants 10 -12 years of age received LTG up to a maximum dose of: 3 milligrams/kilograms (mg/kg)/day or 100 mg/day, whichever was less; or 6 mg/kg/day or 200 mg/day whichever was less; or 12 mg/kg/day or 300 mg/day whichever was less, depending on their bipolar medication group. Participants 13-17 years of age received LTG up to a maximum dose of 150 mg/day, 300 mg/day, or 400 mg/day depending on their bipolar medication group. Participants took LTG for a duration of up to 18 weeks. | Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. | Participants 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. |
| Period Title: Open-Label Phase | |||
| STARTED | 298 | 0 | 0 |
| COMPLETED | 173 | 0 | 0 |
| NOT COMPLETED | 125 | 0 | 0 |
| Period Title: Open-Label Phase | |||
| STARTED | 0 | 86 | 87 |
| COMPLETED | 0 | 21 | 20 |
| NOT COMPLETED | 0 | 65 | 67 |
Baseline Characteristics
| Arm/Group Title | Placebo | Lamotrigine | Total |
|---|---|---|---|
| Arm/Group Description | Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. | Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. | Total of all reporting groups |
| Overall Participants | 86 | 87 | 173 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
13.5
(2.22)
|
13.4
(2.33)
|
13.5
(2.27)
|
| Gender (Count of Participants) | |||
| Female |
39
45.3%
|
33
37.9%
|
72
41.6%
|
| Male |
47
54.7%
|
54
62.1%
|
101
58.4%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| African American/African Heritage |
9
10.5%
|
9
10.3%
|
18
10.4%
|
| American Indian or Alaska Native |
0
0%
|
1
1.1%
|
1
0.6%
|
| Asian - East Asian Heritage |
1
1.2%
|
0
0%
|
1
0.6%
|
| White - Arabic/North African Heritage |
1
1.2%
|
0
0%
|
1
0.6%
|
| White - White/Caucasian/European Heritage |
71
82.6%
|
71
81.6%
|
142
82.1%
|
| Mixed Race |
4
4.7%
|
6
6.9%
|
10
5.8%
|
Outcome Measures
| Title | Time From Randomization to the Occurrence of a Bipolar Event (TOBE) |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo | Lamotrigine |
|---|---|---|
| Arm/Group Description | Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. | Participants 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. |
| Measure Participants | 86 | 87 |
| Stratum: Depression, n=22,21 |
50
(3.8)
|
155
(14.7)
|
| Stratum: Mania/Hypomania, n=36, 37 |
120
(12.2)
|
163
(12.2)
|
| Stratum: Mixed Mood, n=28, 29 |
107
(13.8)
|
136
(15.4)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Placebo, Lamotrigine |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0717 |
| Comments | ||
| Method | Log Rank | |
| Comments | A stratified log rank test was performed where the stratification factor was the index mood state at Screen visit. | |
| Title | Time From Randomization to Withdrawal From the Study for Any Cause (TTW) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized ITT Population |
| Arm/Group Title | Placebo | Lamotrigine |
|---|---|---|
| Arm/Group Description | Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. | Participants 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. |
| Measure Participants | 86 | 87 |
| Stratum: Depression, n=22, 21 |
113
(21.4)
|
141
(20.0)
|
| Stratum: Mania/Hypomania, n=36, 37 |
138
(17.3)
|
144
(15.6)
|
| Stratum: Mixed Mood, n=28, 29 |
101
(15.7)
|
106
(16.3)
|
| Title | Time From Randomization to Intervention for a Mood Episode (TIME) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized ITT Population |
| Arm/Group Title | Placebo | Lamotrigine |
|---|---|---|
| Arm/Group Description | Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. | Participants 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. |
| Measure Participants | 86 | 87 |
| Stratum: Depression, n=22, 21 |
62
(5.2)
|
164
(12.7)
|
| Stratum: Mania/Hypomania, n=36, 37 |
129
(11.7)
|
179
(10.8)
|
| Stratum: Mixed Mood, n=28, 29 |
120
(13.7)
|
127
(12.0)
|
| Title | Time From Randomization to Intervention for Depression (TIDep), Mania/Hypomania (TIMan), or a Mixed Episode (TIMix) |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized ITT Population |
| Arm/Group Title | Placebo | Lamotrigine |
|---|---|---|
| Arm/Group Description | Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. | Participants 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. |
| Measure Participants | 86 | 87 |
| TIDep: Depression, n=22, 21 |
61
(1.5)
|
46
(1.5)
|
| TIDep: Mania/Hypomania, n=36, 37 |
NA
(NA)
|
NA
(NA)
|
| TIDep: Mixed Mood, n=28, 29 |
59
(2.6)
|
159
(NA)
|
| TIMan: Depression, n=22, 21 |
74
(3.9)
|
182
(NA)
|
| TIMan: Mania/Hypomania, n=36, 37 |
139
(11.5)
|
61
(2.1)
|
| TIMan: Mixed Mood, n=28, 29 |
105
(7.3)
|
148
(8.5)
|
| TIMix: Depression, n=22, 21 |
37
(1.3)
|
158
(NA)
|
| TIMix: Mania/Hypomania, n=36, 37 |
135
(6.3)
|
194
(7.5)
|
| TIMix: Mixed Mood, n=28, 29 |
160
(10.7)
|
57
(2.5)
|
| Title | Number of Participants Experiencing a Relapse/Recurrence to Depression, Mania/Hypomania, or Mixed Mood State |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized ITT Population. Only those participants requiring intervention to treat either the emergence of, or a change, in bipolar symptoms were analyzed. |
| Arm/Group Title | Placebo | Lamotrigine |
|---|---|---|
| Arm/Group Description | Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. | Participants 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. |
| Measure Participants | 31 | 18 |
| Depression |
5
5.8%
|
3
3.4%
|
| Mania/hypomania |
16
18.6%
|
6
6.9%
|
| Mixed episode state |
10
11.6%
|
9
10.3%
|
| Title | Number of Participants Experiencing a Relapse/Recurrence Within the First 30, 90, and 180 Days in the Randomized Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized ITT Population. Only those participants requiring intervention to treat either the emergence of, or a change, in bipolar symptoms were analyzed. |
| Arm/Group Title | Placebo | Lamotrigine |
|---|---|---|
| Arm/Group Description | Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. | Participants 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. |
| Measure Participants | 31 | 18 |
| Mania/hypomania, 30 days, n=16, 6 |
9
10.5%
|
2
2.3%
|
| Mania/hypomania, 90 days, n=16, 6 |
12
14%
|
4
4.6%
|
| Mania/hypomania, 180 days, n=16, 6 |
16
18.6%
|
5
5.7%
|
| Depression, 30 days, n=5, 3 |
1
1.2%
|
1
1.1%
|
| Depression, 90 days, n=5, 3 |
5
5.8%
|
2
2.3%
|
| Depression, 180 days, n=5, 3 |
5
5.8%
|
3
3.4%
|
| Mixed mood state, 30 days, n= 10, 9 |
3
3.5%
|
2
2.3%
|
| Mixed mood state, 90 days, n= 10, 9 |
7
8.1%
|
6
6.9%
|
| Mixed mood state, 180 days, n= 10, 9 |
10
11.6%
|
8
9.2%
|
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Open-Label ITT population: all participants who entered the Open-Label Phase and received at least one dose of LTG. |
| Arm/Group Title | LTG: Open-Label Phase |
|---|---|
| Arm/Group Description | Participants (par.) received lamotrigine (LTG) up to a maximum dose depending on their age and concomitant bipolar medication group. Participants 10 -12 years of age received LTG up to a maximum dose of : 3 milligrams/kilograms (mg/kg)/day or 100 mg/day, whichever was less; or 6 mg/kg/day or 200 mg/day whichever was less; or 12 mg/kg/day or 300 mg/day whichever was less, depending on their bipolar medication group. Participants 13-17 years of age received LTG up to a maximum dose of 150 mg/day, 300 mg/day, or 400 mg/day depending on their bipolar medication group. Participants took LTG for a duration of up to 18 weeks. |
| Measure Participants | 298 |
| Week 1 |
-2.1
(0.22)
|
| Week 2 |
-2.9
(0.28)
|
| Week 3 |
-3.7
(0.28)
|
| Week 4 |
-3.8
(0.30)
|
| Week 5 |
-4.3
(0.30)
|
| Week 6 |
-4.7
(0.30)
|
| Week 7 |
-5.1
(0.30)
|
| Week 8 |
-4.9
(0.31)
|
| Week 9 |
-5.6
(0.30)
|
| Week 10 |
-6.1
(0.29)
|
| Week 11 |
-6.4
(0.30)
|
| Week 12 |
-6.6
(0.32)
|
| Week 13 |
-6.7
(0.32)
|
| Week 14 |
-6.8
(0.34)
|
| Week 15 |
-6.8
(0.40)
|
| Week 16 |
-6.8
(0.41)
|
| Week 17 |
-6.5
(0.53)
|
| Week 18 |
-6.5
(0.70)
|
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized ITT Population |
| Arm/Group Title | Placebo | Lamotrigine |
|---|---|---|
| Arm/Group Description | Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. | Participants 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. |
| Measure Participants | 86 | 87 |
| Week 1 |
0.8
(0.30)
|
0.5
(0.31)
|
| Week 2 |
1.5
(0.37)
|
1.1
(0.37)
|
| Week 3 |
1.3
(0.36)
|
0.6
(0.36)
|
| Week 4 |
1.2
(0.39)
|
1.0
(0.39)
|
| Week 6 |
1.9
(0.49)
|
1.5
(0.47)
|
| Week 8 |
1.9
(0.47)
|
1.7
(0.45)
|
| Week 10 |
1.4
(0.44)
|
1.5
(0.41)
|
| Week 12 |
1.4
(0.40)
|
1.2
(0.39)
|
| Week 16 |
2.2
(0.48)
|
1.8
(0.47)
|
| Week 20 |
1.5
(0.50)
|
2.5
(0.46)
|
| Week 24 |
1.7
(0.53)
|
1.8
(0.51)
|
| Week 28 |
1.6
(0.61)
|
2.3
(0.57)
|
| Week 32 |
1.0
(0.72)
|
1.9
(0.72)
|
| Week 36 |
2.3
(0.63)
|
1.9
(0.63)
|
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Open-Label ITT Population |
| Arm/Group Title | LTG: Open-Label Phase |
|---|---|
| Arm/Group Description | Participants (par.) received lamotrigine (LTG) up to a maximum dose depending on their age and concomitant bipolar medication group. Participants 10 -12 years of age received LTG up to a maximum dose of: 3 milligrams/kilograms (mg/kg)/day or 100 mg/day, whichever was less; or 6 mg/kg/day or 200 mg/day whichever was less; or 12 mg/kg/day or 300 mg/day whichever was less, depending on their bipolar medication group. Participants 13-17 years of age received LTG up to a maximum dose of 150 mg/day, 300 mg/day, or 400 mg/day depending on their bipolar medication group. Participants took LTG for a duration of up to 18 weeks. |
| Measure Participants | 298 |
| Week 4 |
-2.7
(0.25)
|
| Week 8 |
-3.3
(0.27)
|
| Week 12 |
-4.3
(0.28)
|
| Week 16 |
-4.5
(0.33)
|
| Week 18 |
-5.0
(0.52)
|
| Title | Change From Randomization in the Quick Inventory of Depressive Symptomatology - Self-report Adolescent Version (QIDS-A17-SR) at Each Visit in the Randomized Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized ITT Population |
| Arm/Group Title | Placebo | Lamotrigine |
|---|---|---|
| Arm/Group Description | Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. | Participants 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. |
| Measure Participants | 86 | 87 |
| Week 8 |
1.6
(0.47)
|
1.2
(0.48)
|
| Week 16 |
1.6
(0.60)
|
1.4
(0.58)
|
| Week 24 |
1.0
(0.60)
|
1.5
(0.56)
|
| Week 32 |
0.6
(0.66)
|
0.2
(0.63)
|
| Week 36 |
0.9
(0.66)
|
0.8
(0.68)
|
| Title | Change From Baseline in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Open-Label Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Open-Label ITT Population |
| Arm/Group Title | LTG: Open-Label Phase |
|---|---|
| Arm/Group Description | Participants (par.) received lamotrigine (LTG) up to a maximum dose depending on their age and concomitant bipolar medication group. Participants 10 -12 years of age received LTG up to a maximum dose of: 3 milligrams/kilograms (mg/kg)/day or 100 mg/day, whichever was less; or 6 mg/kg/day or 200 mg/day whichever was less; or 12 mg/kg/day or 300 mg/day whichever was less, depending on their bipolar medication group. Participants 13-17 years of age received LTG up to a maximum dose of 150 mg/day, 300 mg/day, or 400 mg/day depending on their bipolar medication group. Participants took LTG for a duration of up to 18 weeks. |
| Measure Participants | 298 |
| Week 1 |
-0.4
(0.05)
|
| Week 2 |
-0.6
(0.05)
|
| Week 3 |
-0.9
(0.06)
|
| Week 4 |
-1.0
(0.06)
|
| Week 5 |
-1.2
(0.06)
|
| Week 6 |
-1.3
(0.06)
|
| Week 7 |
-1.4
(0.07)
|
| Week 8 |
-1.5
(0.07)
|
| Week 9 |
-1.6
(0.07)
|
| Week 10 |
-1.8
(0.07)
|
| Week 11 |
-1.9
(0.07)
|
| Week 12 |
-2.1
(0.07)
|
| Week 13 |
-2.1
(0.07)
|
| Week 14 |
-2.1
(0.07)
|
| Week 15 |
-2.1
(0.08)
|
| Week 16 |
-2.1
(0.10)
|
| Week 17 |
-2.0
(0.12)
|
| Week 18 |
-2.1
(0.15)
|
| Title | Change From Randomization in the Clinical Global Impressions - Bipolar, Severity of Illness (CGI-BP[S]) at Each Visit in the Randomized Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized ITT Population |
| Arm/Group Title | Placebo | Lamotrigine |
|---|---|---|
| Arm/Group Description | Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. | Participants 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. |
| Measure Participants | 86 | 87 |
| Week 1 |
0.2
(0.09)
|
0.0
(0.09)
|
| Week 2 |
0.4
(0.12)
|
0.2
(0.12)
|
| Week 3 |
0.4
(0.12)
|
0.2
(0.12)
|
| Week 4 |
0.6
(0.13)
|
0.3
(0.13)
|
| Week 6 |
0.8
(0.15)
|
0.4
(0.15)
|
| Week 8 |
0.7
(0.15)
|
0.4
(0.14)
|
| Week 10 |
0.4
(0.13)
|
0.6
(0.13)
|
| Week 12 |
0.5
(0.14)
|
0.4
(0.14)
|
| Week 16 |
0.6
(0.17)
|
0.6
(0.15)
|
| Week 20 |
0.5
(0.17)
|
0.8
(0.16)
|
| Week 24 |
0.4
(0.17)
|
0.6
(0.16)
|
| Week 28 |
0.3
(0.17)
|
0.5
(0.16)
|
| Week 32 |
0.2
(0.19)
|
0.5
(0.20)
|
| Week 36 |
0.4
(0.19)
|
0.3
(0.21)
|
| Title | Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Open-label Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LTG: Open-Label Phase |
|---|---|
| Arm/Group Description | Participants (par.) received lamotrigine (LTG) up to a maximum dose depending on their age and concomitant bipolar medication group. Participants 10 -12 years of age received LTG up to a maximum dose of: 3 milligrams/kilograms (mg/kg)/day or 100 mg/day, whichever was less; or 6 mg/kg/day or 200 mg/day whichever was less; or 12 mg/kg/day or 300 mg/day whichever was less, depending on their bipolar medication group. Participants 13-17 years of age received LTG up to a maximum dose of 150 mg/day, 300 mg/day, or 400 mg/day depending on their bipolar medication group. Participants took LTG for a duration of up to 18 weeks. |
| Measure Participants | 298 |
| Week 1, n=290 |
3.6
(0.80)
|
| Week 2, n=278 |
3.3
(0.90)
|
| Week 3, n=270 |
3.1
(0.96)
|
| Week 4, n=265 |
3.0
(1.03)
|
| Week 5, n=258 |
2.8
(1.01)
|
| Week 6, n=243 |
2.7
(1.05)
|
| Week 7, n=246 |
2.5
(1.07)
|
| Week 8, n=236 |
2.5
(1.09)
|
| Week 9, n=227 |
2.3
(1.05)
|
| Week 10, n=205 |
2.2
(1.09)
|
| Week 11, n=181 |
2.2
(0.92)
|
| Week 12, n=168 |
2.0
(0.87)
|
| Week 13, n=141 |
1.9
(0.85)
|
| Week 14, n=118 |
1.9
(0.69)
|
| Week 15, n=93 |
1.8
(0.71)
|
| Week 16, n=72 |
2.0
(0.89)
|
| Week 17, n=42 |
2.0
(0.70)
|
| Week 18, n=28 |
2.0
(0.88)
|
| Title | Summary of Clinical Global Impressions - Bipolar - Improvement of Illness (CGI-BP [I]) Scores During Randomized Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | Placebo | Lamotrigine |
|---|---|---|
| Arm/Group Description | Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. | Participants 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. |
| Measure Participants | 86 | 87 |
| Week 1, n=84, 85 |
3.3
(1.40)
|
3.3
(1.37)
|
| Week 2, n=82, 81 |
3.7
(1.48)
|
3.6
(1.38)
|
| Week 3, n=74, 75 |
3.6
(1.39)
|
3.6
(1.34)
|
| Week 4, n=65, 70 |
3.6
(1.51)
|
3.6
(1.35)
|
| Week 6, n=58, 64 |
3.8
(1.64)
|
3.4
(1.49)
|
| Week 8, n=51, 60 |
3.5
(1.72)
|
3.6
(1.47)
|
| Week 10, n=45, 55 |
3.3
(1.64)
|
3.8
(1.19)
|
| Week 12, n=45, 49 |
3.3
(1.52)
|
3.4
(1.29)
|
| Week 16, n=43, 50 |
3.4
(1.73)
|
3.5
(1.37)
|
| Week 20, n=37, 43 |
3.0
(1.48)
|
3.8
(1.36)
|
| Week 24, n=34, 36 |
3.0
(1.59)
|
3.4
(1.44)
|
| Week 28, n=29, 32 |
2.7
(1.56)
|
3.5
(1.44)
|
| Week 32, n=28, 27 |
3.0
(1.63)
|
3.5
(1.28)
|
| Week 36, n=27, 24 |
3.0
(1.68)
|
3.6
(1.10)
|
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | LTG: Open-Label Phase |
|---|---|
| Arm/Group Description | Participants (par.) received lamotrigine (LTG) up to a maximum dose depending on their age and concomitant bipolar medication group. Participants 10 -12 years of age received LTG up to a maximum dose of: 3 milligrams/kilograms (mg/kg)/day or 100 mg/day, whichever was less; or 6 mg/kg/day or 200 mg/day whichever was less; or 12 mg/kg/day or 300 mg/day whichever was less, depending on their bipolar medication group. Participants 13-17 years of age received LTG up to a maximum dose of 150 mg/day, 300 mg/day, or 400 mg/day depending on their bipolar medication group. Participants took LTG for a duration of up to 18 weeks. |
| Measure Participants | 298 |
| Week 1, n=297 |
27
31.4%
|
| Week 2, n=297 |
46
53.5%
|
| Week 3, n=297 |
72
83.7%
|
| Week 4, n=297 |
86
100%
|
| Week 5, n=297 |
113
131.4%
|
| Week 6, n=297 |
124
144.2%
|
| Week 7, n=297 |
138
160.5%
|
| Week 8, n=297 |
140
162.8%
|
| Week 9, n=297 |
159
184.9%
|
| Week 10, n=297 |
176
204.7%
|
| Week 11, n=297 |
182
211.6%
|
| Week 12, n=297 |
195
226.7%
|
| Week 13, n=297 |
205
238.4%
|
| Week 14, n=297 |
211
245.3%
|
| Week 15, n=297 |
210
244.2%
|
| Week 16, n=297 |
209
243%
|
| Week 17, n=297 |
208
241.9%
|
| Week 18, n=297 |
206
239.5%
|
| Title | 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 |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized ITT Population |
| Arm/Group Title | Placebo | Lamotrigine |
|---|---|---|
| Arm/Group Description | Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. | Participants 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. |
| Measure Participants | 86 | 87 |
| Week 1 |
31
36%
|
31
35.6%
|
| Week 2 |
25
29.1%
|
22
25.3%
|
| Week 3 |
24
27.9%
|
21
24.1%
|
| Week 4 |
22
25.6%
|
19
21.8%
|
| Week 6 |
20
23.3%
|
23
26.4%
|
| Week 8 |
22
25.6%
|
19
21.8%
|
| Week 10 |
22
25.6%
|
12
13.8%
|
| Week 12 |
21
24.4%
|
17
19.5%
|
| Week 16 |
21
24.4%
|
16
18.4%
|
| Week 20 |
21
24.4%
|
14
16.1%
|
| Week 24 |
21
24.4%
|
15
17.2%
|
| Week 28 |
22
25.6%
|
15
17.2%
|
| Week 32 |
19
22.1%
|
15
17.2%
|
| Week 36 |
20
23.3%
|
13
14.9%
|
| Title | Change From Baseline in the Young Mania Rating Scale (YMRS) at Each Visit in the Open-Label Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Open-Label ITT Population |
| Arm/Group Title | LTG: Open-Label Phase |
|---|---|
| Arm/Group Description | Participants (par.) received lamotrigine (LTG) up to a maximum dose depending on their age and concomitant bipolar medication group. Participants 10 -12 years of age received LTG up to a maximum dose of: 3 milligrams/kilograms (mg/kg)/day or 100 mg/day, whichever was less; or 6 mg/kg/day or 200 mg/day whichever was less; or 12 mg/kg/day or 300 mg/day whichever was less, depending on their bipolar medication group. Participants 13-17 years of age received LTG up to a maximum dose of 150 mg/day, 300 mg/day, or 400 mg/day depending on their bipolar medication group. Participants took LTG for a duration of up to 18 weeks. |
| Measure Participants | 298 |
| Week 1 |
-3.2
(0.39)
|
| Week 2 |
-4.8
(0.42)
|
| Week 3 |
-6.4
(0.45)
|
| Week 4 |
-6.5
(0.46)
|
| Week 5 |
-7.5
(0.50)
|
| Week 6 |
-8.4
(0.50)
|
| Week 7 |
-9.1
(0.51)
|
| Week 8 |
-8.8
(0.48)
|
| Week 9 |
-9.6
(0.48)
|
| Week 10 |
-10.3
(0.49)
|
| Week 11 |
-11.1
(0.48)
|
| Week 12 |
-11.6
(0.53)
|
| Week 13 |
-12.0
(0.58)
|
| Week 14 |
-12.0
(0.59)
|
| Week 15 |
-12.4
(0.63)
|
| Week 16 |
-12.3
(0.78)
|
| Week 17 |
-12.2
(0.88)
|
| Week 18 |
-12.1
(1.43)
|
| Title | Change From Randomization in the Young Mania Rating Scale (YMRS) at Each Visit in the Randomized Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized ITT Population |
| Arm/Group Title | Placebo | Lamotrigine |
|---|---|---|
| Arm/Group Description | Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. | Participants 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. |
| Measure Participants | 86 | 87 |
| Week 1 |
1.3
(0.57)
|
0.4
(0.59)
|
| Week 2 |
2.6
(0.72)
|
2.1
(0.72)
|
| Week 3 |
2.6
(0.69)
|
1.3
(0.71)
|
| Week 4 |
3.7
(0.85)
|
2.0
(0.84)
|
| Week 6 |
4.9
(0.96)
|
2.3
(0.93)
|
| Week 8 |
4.3
(0.98)
|
3.5
(0.93)
|
| Week 10 |
3.5
(0.87)
|
2.9
(0.82)
|
| Week 12 |
3.2
(0.84)
|
1.6
(0.81)
|
| Week 16 |
4.7
(0.93)
|
3.0
(0.89)
|
| Week 20 |
4.8
(0.99)
|
4.5
(0.92)
|
| Week 24 |
4.2
(1.06)
|
2.9
(1.02)
|
| Week 28 |
4.4
(1.04)
|
3.7
(1.01)
|
| Week 32 |
4.5
(1.10)
|
2.6
(1.14)
|
| Week 36 |
3.5
(0.92)
|
1.2
(0.95)
|
| Title | Change From Baseline in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Open-Label Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Open-Label ITT Population |
| Arm/Group Title | LTG: Open-Label Phase |
|---|---|
| Arm/Group Description | Participants (par.) received lamotrigine (LTG) up to a maximum dose depending on their age and concomitant bipolar medication group. Participants 10 -12 years of age received LTG up to a maximum dose of: 3 milligrams/kilograms (mg/kg)/day or 100 mg/day, whichever was less; or 6 mg/kg/day or 200 mg/day whichever was less; or 12 mg/kg/day or 300 mg/day whichever was less, depending on their bipolar medication group. Participants 13-17 years of age received LTG up to a maximum dose of 150 mg/day, 300 mg/day, or 400 mg/day depending on their bipolar medication group. Participants took LTG for a duration of up to 18 weeks. |
| Measure Participants | 298 |
| Week 4 |
-4.7
(0.57)
|
| Week 8 |
-6.0
(0.62)
|
| Week 12 |
-7.4
(0.62)
|
| Week 16 |
-8.2
(0.72)
|
| Week 18 |
-9.3
(1.29)
|
| Title | Change From Randomization in the Parent Version of the Young Mania Rating Scale (P-YMRS) at Each Visit in the Randomized Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized ITT Population |
| Arm/Group Title | Placebo | Lamotrigine |
|---|---|---|
| Arm/Group Description | Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. | Participants 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. |
| Measure Participants | 86 | 87 |
| Week 8 |
4.9
(0.93)
|
4.3
(0.95)
|
| Week 16 |
2.7
(1.13)
|
2.6
(1.09)
|
| Week 24 |
5.3
(1.35)
|
5.7
(1.29)
|
| Week 32 |
5.1
(1.33)
|
6.0
(1.32)
|
| Week 36 |
5.3
(1.33)
|
4.5
(1.36)
|
| Title | Change From Baseline in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Open-Label Phase |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Open-Label ITT Population |
| Arm/Group Title | LTG: Open-Label Phase |
|---|---|
| Arm/Group Description | Participants (par.) received lamotrigine (LTG) up to a maximum dose depending on their age and concomitant bipolar medication group. Participants 10 -12 years of age received LTG up to a maximum dose of: 3 milligrams/kilograms (mg/kg)/day or 100 mg/day, whichever was less; or 6 mg/kg/day or 200 mg/day whichever was less; or 12 mg/kg/day or 300 mg/day whichever was less, depending on their bipolar medication group. Participants 13-17 years of age received LTG up to a maximum dose of 150 mg/day, 300 mg/day, or 400 mg/day depending on their bipolar medication group. Participants took LTG for a duration of up to 18 weeks. |
| Measure Participants | 298 |
| Week 4 |
-4.0
(0.36)
|
| Week 8 |
-5.7
(0.43)
|
| Week 12 |
-6.7
(0.47)
|
| Week 16 |
-7.1
(0.56)
|
| Week 18 |
-8.2
(1.07)
|
| Title | Change From Randomization in the Conners' Global Index - Parent Version (CGI-P) at Each Visit in the Randomized Phase. |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Randomized ITT Population |
| Arm/Group Title | Placebo | Lamotrigine |
|---|---|---|
| Arm/Group Description | Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. | Participants 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. |
| Measure Participants | 86 | 87 |
| Week 8 |
3.1
(0.75)
|
2.1
(0.77)
|
| Week 16 |
3.4
(0.92)
|
1.2
(0.90)
|
| Week 24 |
2.4
(1.12)
|
3.1
(1.05)
|
| Week 32 |
2.7
(1.10)
|
2.6
(1.08)
|
| Week 36 |
1.5
(1.00)
|
0.5
(1.03)
|
Adverse Events
| Time Frame | On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Open-Label or Double-Blind Taper and Follow-up Phase (up to Taper Week 4). | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | On-treatment SAEs and non-serious AEs, were reported for ITT population (Open-Label and Randomized Phase), comprised of all participants who were randomized to LTG or placebo (only for Randomized Phase) and received at least one dose of the investigational product. | |||||
| Arm/Group Title | Open-Label and Open-Label Taper Phases: LTG | Randomized and Double-blind Taper Phases: Placebo | Randomized and Double-blind Taper Phases: LTG | |||
| Arm/Group Description | Participants (par.) received lamotrigine (LTG) up to a maximum dose depending on their age and concomitant bipolar medication group. Participants 10 -12 years of age received LTG up to a maximum dose of : 3 milligrams/kilograms (mg/kg)/day or 100 mg/day, whichever was less; or 6 mg/kg/day or 200 mg/day whichever was less; or 12 mg/kg/day or 300 mg/day whichever was less, depending on their bipolar medication group. Participants 13-17 years of age received LTG up to a maximum dose of 150 mg/day, 300 mg/day, or 400 mg/day depending on their bipolar medication group. Participants took LTG for a duration of up to 18 weeks. Participants discontinuing from the study during the Open-Label Phase entered an open Taper and Follow-up Phase.The Taper and Follow-up Phase may last up to 4 weeks, dependent on the dose of LTG the participant received during the Open-Label Phase. | Participants received matching placebo in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. Participants completing the Randomized Phase entered Double-Blind Taper and Follow-up Phase. The Taper and Follow-up Phase may last up to 4 weeks. The participant received Placebo during this Phase. | Participants received LTG equivalent to the dose established in the Open-Label Phase. Participants received LTG tablets in the evening for participants taking one dose and for participants taking two divided doses, one dose in the morning and one dose in the evening, for a duration of up to 36 weeks. Participants completing the Randomized Phase entered Double-Blind Taper and Follow-up Phase. The Taper and Follow-up Phase may last up to 4 weeks, dependent on the dose of LTG the participant received during the Randomized Phase. | |||
All Cause Mortality |
||||||
| Open-Label and Open-Label Taper Phases: LTG | Randomized and Double-blind Taper Phases: Placebo | Randomized and Double-blind Taper Phases: LTG | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Open-Label and Open-Label Taper Phases: LTG | Randomized and Double-blind Taper Phases: Placebo | Randomized and Double-blind Taper Phases: LTG | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 19/298 (6.4%) | 5/86 (5.8%) | 1/87 (1.1%) | |||
| General disorders | ||||||
| Irritability | 2/298 (0.7%) | 0/86 (0%) | 0/87 (0%) | |||
| Infections and infestations | ||||||
| Infectious mononucleosis | 0/298 (0%) | 1/86 (1.2%) | 0/87 (0%) | |||
| Urinary tract infection | 0/298 (0%) | 1/86 (1.2%) | 0/87 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Intentional overdose | 0/298 (0%) | 1/86 (1.2%) | 0/87 (0%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Neoplasm | 1/298 (0.3%) | 0/86 (0%) | 0/87 (0%) | |||
| Psychiatric disorders | ||||||
| Suicidal ideation | 5/298 (1.7%) | 1/86 (1.2%) | 0/87 (0%) | |||
| Agitation | 3/298 (1%) | 0/86 (0%) | 0/87 (0%) | |||
| Mania | 3/298 (1%) | 1/86 (1.2%) | 0/87 (0%) | |||
| Aggression | 1/298 (0.3%) | 0/86 (0%) | 0/87 (0%) | |||
| Anxiety | 1/298 (0.3%) | 0/86 (0%) | 0/87 (0%) | |||
| Bipolar I disorder | 1/298 (0.3%) | 1/86 (1.2%) | 0/87 (0%) | |||
| Bipolar disorder | 1/298 (0.3%) | 0/86 (0%) | 0/87 (0%) | |||
| Impulsive behaviour | 1/298 (0.3%) | 0/86 (0%) | 0/87 (0%) | |||
| Intentional self-injury | 1/298 (0.3%) | 0/86 (0%) | 0/87 (0%) | |||
| Pressure of speech | 1/298 (0.3%) | 0/86 (0%) | 0/87 (0%) | |||
| Emotional disorder | 0/298 (0%) | 0/86 (0%) | 1/87 (1.1%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Asthma | 1/298 (0.3%) | 0/86 (0%) | 0/87 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Rash | 1/298 (0.3%) | 0/86 (0%) | 0/87 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Open-Label and Open-Label Taper Phases: LTG | Randomized and Double-blind Taper Phases: Placebo | Randomized and Double-blind Taper Phases: LTG | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 177/298 (59.4%) | 41/86 (47.7%) | 45/87 (51.7%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal pain upper | 47/298 (15.8%) | 3/86 (3.5%) | 5/87 (5.7%) | |||
| Nausea | 39/298 (13.1%) | 0/86 (0%) | 0/87 (0%) | |||
| Diarrhoea | 23/298 (7.7%) | 0/86 (0%) | 0/87 (0%) | |||
| Vomiting | 25/298 (8.4%) | 3/86 (3.5%) | 5/87 (5.7%) | |||
| General disorders | ||||||
| Irritability | 16/298 (5.4%) | 14/86 (16.3%) | 7/87 (8%) | |||
| Fatigue | 17/298 (5.7%) | 0/86 (0%) | 0/87 (0%) | |||
| Pyrexia | 0/298 (0%) | 5/86 (5.8%) | 2/87 (2.3%) | |||
| Infections and infestations | ||||||
| Nasopharyngitis | 25/298 (8.4%) | 5/86 (5.8%) | 7/87 (8%) | |||
| Influenza | 0/298 (0%) | 2/86 (2.3%) | 7/87 (8%) | |||
| Nervous system disorders | ||||||
| Headache | 106/298 (35.6%) | 18/86 (20.9%) | 18/87 (20.7%) | |||
| Dizziness | 24/298 (8.1%) | 0/86 (0%) | 0/87 (0%) | |||
| Psychiatric disorders | ||||||
| Insomnia | 23/298 (7.7%) | 5/86 (5.8%) | 6/87 (6.9%) | |||
| Suicidal ideation | 16/298 (5.4%) | 0/86 (0%) | 0/87 (0%) | |||
| Agitation | 0/298 (0%) | 1/86 (1.2%) | 5/87 (5.7%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 21/298 (7%) | 4/86 (4.7%) | 7/87 (8%) | |||
| Oropharyngeal pain | 30/298 (10.1%) | 2/86 (2.3%) | 7/87 (8%) | |||
| Nasal congestion | 0/298 (0%) | 6/86 (7%) | 6/87 (6.9%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
| Name/Title | GSK Response Center |
|---|---|
| Organization | GlaxoSmithKline |
| Phone | 866-435-7343 |
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00723450
Other Study ID Numbers:
- SCA102833
First Posted:
Jul 28, 2008
Last Update Posted:
Jan 9, 2017
Last Verified:
Nov 1, 2016