Lamictal as Add-on Treatment for Bipolar I Disorder in Pediatric Patients

The Evaluation of Lamictal as an Add-on Treatment for Bipolar I Disorder in Children and Adolescents, 10 to 17 Years of Age

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).

Study Overview

• Status: Completed
• Conditions: Bipolar Disorder
• Intervention / Treatment: Drug: lamictal

• Study Type: Interventional
• Enrollment (Actual): 301
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Dothan, Alabama, United States, 36305
      • GSK Investigational Site
  • Arizona
    • Scottsdale, Arizona, United States, 85252
      • GSK Investigational Site
  • California
    • San Diego, California, United States, 92108
      • GSK Investigational Site
    • Stanford, California, United States, 94304
      • GSK Investigational Site
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • GSK Investigational Site
  • Florida
    • Bradenton, Florida, United States, 34201
      • GSK Investigational Site
    • Gainesville, Florida, United States, 32607
      • GSK Investigational Site
    • Jacksonville, Florida, United States, 32216
      • GSK Investigational Site
    • Orlando, Florida, United States, 32839
      • GSK Investigational Site
    • Tampa, Florida, United States, 33613
      • GSK Investigational Site
    • Winter Park, Florida, United States, 32789
      • GSK Investigational Site
  • Georgia
    • Smyrna, Georgia, United States, 30080
      • GSK Investigational Site
  • Illinois
    • Libertyville, Illinois, United States, 60048
      • GSK Investigational Site
    • Naperville, Illinois, United States, 60563
      • GSK Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • GSK Investigational Site
  • Kansas
    • Overland Park, Kansas, United States, 66211
      • GSK Investigational Site
    • Wichita, Kansas, United States, 67206
      • GSK Investigational Site
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • GSK Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21208
      • GSK Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • GSK Investigational Site
    • Boston, Massachusetts, United States, 02115
      • GSK Investigational Site
    • Springfield, Massachusetts, United States, 01199
      • GSK Investigational Site
    • Worcester, Massachusetts, United States, 01655
      • GSK Investigational Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • GSK Investigational Site
  • Missouri
    • St. Charles, Missouri, United States, 63304
      • GSK Investigational Site
  • Nebraska
    • Lincoln, Nebraska, United States, 68526
      • GSK Investigational Site
  • New Jersey
    • Piscataway, New Jersey, United States, 08854
      • GSK Investigational Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • GSK Investigational Site
  • New York
    • Mount Kisco, New York, United States, 10549
      • GSK Investigational Site
    • Stony Brook, New York, United States, 11794-8790
      • GSK Investigational Site
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27517
      • GSK Investigational Site
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • GSK Investigational Site
    • Cincinnati, Ohio, United States, 45219
      • GSK Investigational Site
    • Cleveland, Ohio, United States, 44106
      • GSK Investigational Site
    • Columbus, Ohio, United States, 43210
      • GSK Investigational Site
    • Toledo, Ohio, United States, 43609
      • GSK Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • GSK Investigational Site
  • Texas
    • Dallas, Texas, United States, 75235
      • GSK Investigational Site
    • Houston, Texas, United States, 77030
      • GSK Investigational Site
    • Houston, Texas, United States, 77008
      • GSK Investigational Site
    • Houston, Texas, United States, 77007
      • GSK Investigational Site
  • Utah
    • Salt Lake City, Utah, United States, 84105
      • GSK Investigational Site
  • Virginia
    • Roanoke, Virginia, United States, 24013
      • GSK Investigational Site
  • Washington
    • Kirkland, Washington, United States, 98033
      • GSK Investigational Site
    • Seattle, Washington, United States, 98105
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: placebo; Placebo Controlled	Drug: lamictal; Flexible Dosing
EXPERIMENTAL: lamictal; Flexible Dosing	Drug: lamictal; Flexible Dosing

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	From randomization until Week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	From randomization until withdrawal from the study for any cause (up to Week 36)
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).	From randomization until intervention administered for a mood episode (up to Week 36)
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).	From randomization until intervention administered for depression, mania/hypomania or a mixed episode (up to Week 36)
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.	From randomization until a relapse/recurrence to depression, mania/hypomania, or mixed mood state (up to Week 36)
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.	From randomization up to Week 36
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.	Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18
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.	Randomization and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, and 36
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.	Baseline and Weeks 4, 8, 12, 16, and 18
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.	Randomization and Weeks 8, 16, 24, 32, and 36
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.	Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18
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.	Randomization and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, and 36
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.	Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18
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.	Randomization weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32 and 36
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).	Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18
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).	Randomization and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, and 36
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.	Baseline and Weeks 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, and 18
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.	Randomization and Weeks 1, 2, 3, 4, 6, 8, 10, 12, 16, 20, 24, 28, 32, and 36
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.	Baseline and Weeks 4, 8, 12, 16, and 18
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.	Randomization and Weeks 8, 16, 24, 32, and 36
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.	Baseline and Weeks 4, 8, 12, 16, and 18
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.	Randomization and Weeks 8, 16, 24, 32, and 36

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Findling RL, Chang K, Robb A, Foster VJ, Horrigan J, Krishen A, Wamil A, Kraus JE, DelBello M. Adjunctive Maintenance Lamotrigine for Pediatric Bipolar I Disorder: A Placebo-Controlled, Randomized Withdrawal Study. J Am Acad Child Adolesc Psychiatry. 2015 Dec;54(12):1020-1031.e3. doi: 10.1016/j.jaac.2015.09.017. Epub 2015 Oct 14.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (ACTUAL): August 1, 2013
• Study Completion (ACTUAL): August 1, 2013

Study Registration Dates

• First Submitted: July 24, 2008
• First Submitted That Met QC Criteria: July 24, 2008
• First Posted (ESTIMATE): July 28, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): January 9, 2017
• Last Update Submitted That Met QC Criteria: November 18, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Bipolar I pediatric lamictal adolescent
• Additional Relevant MeSH Terms: Mental Disorders; Bipolar and Related Disorders; Bipolar Disorder; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anticonvulsants; Sodium Channel Blockers; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Lamotrigine
• Other Study ID Numbers: SCA102833

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Informed Consent Form
   Information identifier: SCA102833
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: SCA102833
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: SCA102833
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: SCA102833
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: SCA102833
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: SCA102833
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Annotated Case Report Form
   Information identifier: SCA102833
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register