E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Mental Disorders [F03] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10004938 |
E.1.2 | Term | Bipolar disorders |
E.1.2 | System Organ Class | 100000004873 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is to compare the efficacy of LAMICTAL versus placebo in delaying the time to the occurrence of a bipolar event in subjects who have been responsive to open-label LAMICTAL treatment added to their conventional mono- or dual-bipolar therapy. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the safety and long-term tolerability of LAMICTAL compared to placebo.
• To evaluate quality of life and satisfaction, as well as psychological, social, and school functioning in patients receiving LAMICTAL compared to placebo.
• To evaluate the efficacy of LAMICTAL compared to placebo in the treatment of different bipolar I subtypes (i.e., manic/hypomanic, depressed, mixed).
• To determine the proportion of child and adolescent subjects with bipolar I disorder who meet stabilization criteria during the Open-label Phase with LAMICTAL as add-on therapy. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
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E.4 | Principal 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the time from randomization to the occurrence of a bipolar event (TOBE). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
- Time from randomization to withdrawal from the study for any cause (TTW).
- Time from randomization to intervention for a mood episode (TIME).
- Time from randomization to intervention for depression (TIDep), mania/hypomania (TIMan), or a mixed episode (TIMix).
- Proportion of subjects experiencing a relapse/recurrence to depression, mania/hypomania, or mixed mood state.
- Proportion of subjects experiencing a relapse/recurrence within the first 30, 90, and 180 days of the Randomized Phase.
• Change from Baseline/Randomization in the Quick Inventory of Depressive Symptomatology – Clinician interview, semi-structured, adolescent version (QIDSA17-C) at each visit.
• Change from Baseline/Randomization in the Quick Inventory of Depressive
Symptomatology – self-report adolescent version (QIDS-A17-SR) at each visit.
• Change from Baseline/Randomization in the Clinical Global Impressions – Bipolar, Severity of Illness (CGI-BP[S]) at each visit.
• Change in the Clinical Global Impressions – Bipolar, Improvement of Illness (CGIBP[
I]) score at each visit.
• Proportion of subjects considered much improved or very much improved [defined
as a Clinical Global Impression-Bipolar Version, Improvement of Illness (CGIBP[
I]), score of 1 or 2] at each visit compared to Baseline/Randomization.
• Change from Baseline/Randomization in the Young Mania Rating Scale (YMRS) at
each visit.
• Change from Baseline/Randomization in the Parent Version of the Young Mania
Rating Scale (P-YMRS) at each visit.
• Change from Baseline/Randomization in the Conners’ Global Index – Parent
Version (CGI-P) at each visit.
Note: For endpoints noted as being the change from “Baseline/Randomization,” this means “change from Baseline” in the Open |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 11 |