Phase 3
N=420
Lamotrigine Phase III Study in Bipolar I Disorder
Bipolar Disorder
Bottom Line
View on ClinicalTrials.gov: NCT01602510 ↗Enrolled (actual)
420
Serious AEs
1.9%
Results posted
Jan 2017
Primary outcome: Primary: Time to Intervention for Any Mood Episode (TIME) — NA; NA Days — p==0.438
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Lamotrigine (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Dec 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to Intervention for Any Mood Episode (TIME) |
NA; NA | =0.438 |
| SECONDARY Time to Intervention for Manic, Hypomanic or Mixed Episode (TIMan) |
NA; NA | =0.869 |
| SECONDARY Time to Intervention for Depressive Episode (TIDep) |
NA; NA | =0.369 |
| SECONDARY Overall Survival in Study (TIME-SIS). |
183; 188 | =0.927 |
| SECONDARY Change From Baseline in Clinical Global Impression of Improvements (CGI-I) |
2.6; 2.7 | =0.833 |
| SECONDARY Change From Baseline in Clinical Global Impression of Severity (CGI-S) |
0.7; 0.5 | =0.245 |
| SECONDARY Change From Baseline in Hamilton Depression Rating Scale (HAMD) |
3.0; 1.8 | =0.155 |
| SECONDARY Change From Baseline in Young Mania Rating Scale (YMRS) Total Score |
2.4; 2.8 | = 0.661 |
| SECONDARY Change From Baseline of Global Assessment Scale (GAS) Total Score |
-4.7; -4.9 | = 0.945 |
| SECONDARY Change From Baseline in Body Weight |
-0.72; -1.56 | =0.047 sig |
Summary
This registration study in China is a multi-centre, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of lamotrigine in the prevention of recurrence/relapse of mood episodes in subjects with bipolar I disorder. Subjects are bipolar I disorder patients with recent/current manic, hypomanic, mixed or depressive episode. The study will include an open-label phase and a randomized phase. During the open-label phase, subjects will have lamotrigine monotherapy or combination therapy escalation. The target dose of lamotrigine is 200 milligram (mg)/day monotherapy. The duration of treatment in the open-label phase will last 6-16 weeks, until subjects reach a stable dose of lamotrigine. Beginning at week 7 of the open-label phase, subjects who have reached a stable dose of lamotrigine and met response criteria, defined as maintaining a Clinical Global Impression of Severity (CGI-S) score <= 3 for at least 4 continuous weeks and maintaining lamotrigine 200 mg/day monotherapy for at least 1 week, will be eligible to enroll in the double-blind phase of the study. Subjects who have not met response criteria after 16 weeks of participation in the open-label phase will be withdrawn from the study. Subjects will have lamotrigine 200 mg/day monotherapy for at least 1 week prior to randomization. Subjects who have met randomization requirements will be randomized 1:1 to lamotrigine 200 mg/day or placebo for 36 weeks double-blind treatment. After randomization, subjects will be assessed at weekly intervals for the first month, biweekly intervals for the second month, and then at monthly intervals for up to 36 weeks of double-blind treatment. The primary endpoint will be TIME, defined as the time to intervention (addition of pharmacotherapy or electroconvulsive therapy [ECT]) for any mood episode (relapse or recurrence of a depressive, manic, hypomanic or mixed episode) after randomization. The secondary endpoints will include time to intervention for manic, hypomanic or mixed episode (TIMan) and time to intervention for depressive episode (TIDep).The scores on the Hamilton Depression (HAMD), Young Mania Rating Scale (YMRS), CGI-I, CGI-S and Global Assessment Scale (GAS) will be used as indicators for both intensity and duration of mood symptoms during this phase. Subjects who withdraw early from the study prior to week 36 or reach TIME will have a follow-up visit 14 days after the last dose of investigational drug.
Eligibility Criteria
Inclusion Criteria
For open label phase
- Subjects must be able to effectively communicate with study personnel, have the ability to comprehend the key components of the Inform Consent Form and must provide written informed consent to participate in the study prior to any study-specific assessments or procedures.
- An in-patient or out-patient (male or female) and aged >=18 years old.
- Disease to be studied: Has a diagnosis of the following disease as defined by DSM-IV criteria currently or within 60 days:
a)Bipolar I Disorder, most recent episode depressed (296.5x); b)Bipolar I Disorder, most recent episode hypomanic (296.40); c)Bipolar I Disorder, most recent episode manic (296.4x); d)Bipolar I Disorder, most recent episode mixed (296.6x)
- The subject who has a diagnose of "bipolar I disorder, most recent episode depressed (296.5x)" must meet the following criteria:
Has at least one well documented manic, hypomanic or mixed episode, as defined by DSM-IV criteria, within 3 years of enrolment ; The duration of recent/current depressive episode is at least 2 weeks but not longer than 12 months prior to enrolment; For subject with currently experiencing a depressive episode, he/she must have a minimum total score of 18 on the HAMD-17 at s screening.
- The subject who has a diagnosis of "bipolar I disorder, most recent episode hypomanic (296.40)" or "bipolar I disorder, most recent episode manic (296.4x)" or "bipolar I disorder, most recent episode mixed (296.6x)" must meet the following criteria: Has had at least one well documented additional manic, hypomanic or mixed episode and one depressed episode, as defined by DSM-IV criteria, within 3 years of enrolment; Has a duration of the index manic episode of at least 1 week (unless hospitalised) or hypomanic episode of at least 4 days or mixed episode of at least 1 week. In neither case should the index episode be more than 12 months in duration; If the subject's index episode is the subject's initial/current manic mood event, subject must have a minimum score of 10 on the first 11 items of the YMRS at screening; If the subject's index episode is the subject's initial/current mixed mood event, subject must have a minimum score of 10 on the first 11 items of the YMRS, and have a minimum score of 18 on the HAMD-17 at screening.
For randomized double-blind phase
- Has been on Lamotrigine 200 mg/day monotherapy for at least 1 week.
- CGI-S score 35 {BMI = Body weight (in kg) divided by (Height in meters squared).
- Single or average QT interval corrected by Bazette's formulaQTcB or QTc > 450 millisecond (msec); for patients with bundle branch block QTc > 480 msec.
- Has a history of hepatic dysfunction; Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) >= 2 x upper limit of normal (ULN); Alkaline phosphatase (ALP) or total bilirubin > 1.5 x ULN (excluding total bilirubin > 1.5 x ULN but direct bilirubin =3 on item 3 of the HAMD.
- Has tested positive for an illicit drug on lab analysis administered before randomization or alcohol abuse/addiction.
- Has had a change in lamotrigine dosage during the last week of the open-label phase.
Data sourced from ClinicalTrials.gov (NCT01602510). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.