Efficacy, Safety, and Tolerability of Eslicarbazepine Acetate in the Recurrence Prevention of Bipolar I Disorder

Study Overview
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Brief Summary
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This was an extension study consisting of 2 parts. In Part I, all participants received open-label treatment with BIA 2-093 900 mg once daily for 2 weeks. Part II followed a double-blind, parallel-group design in which participants were randomly assigned to treatment with BIA 2-093 300 mg, 900 mg, or 1800 mg once daily. Patients stable in remission continued double-blind therapy until approximately 6 months after the last patient entered Part II.

Detailed Description
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The occurrence of a new manic/depressive episode was considered a treatment failure, and the patient was discontinued from the study. At the end of Part II, 6 months after last patient enrolled and after no longer than approximately 15 months, if patients were still in remission and the investigational product was well-tolerated, patients had the option to enter long-term open-label treatment at the same dosage as used in Part II until a new episode occurred, until marketing was authorized, or until clinical development of BIA 2-093 in the recurrence prevention indication was discontinued. If patients did not enter long-term treatment, an established recurrence prevention medication was prescribed, and BIA 2-093 was tapered off (patients assigned to 1800 mg had the daily dose decreased to 900 mg for 6 days; those assigned to 900 mg or 300 mg received placebo for 6 days).

Official Title
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Extension Study to Investigate the Efficacy, Safety, and Tolerability of Eslicarbazepine Acetate (BIA 2-093) in the Recurrence Prevention of Bipolar I Disorder

Conditions
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Bipolar I Disorder

Intervention / Treatment
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* Drug: BIA 2-093 1800 mg once daily [Group 1 (Part II)]
* Drug: BIA 2-093 900 mg once daily [Group 2 (Part II)]
* Drug: BIA 2-093 300 mg once daily [Group 3 (Part II)]
* Drug: BIA 2-093 900 mg (Part I)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: signed the Informed consent form (ICF) completed the 3-week treatment period in Protocol with identification number SCO/BIA-2093-203 or Protocol with identification number PRA/BIA-2093-204 and shown response to treatment, defined as ≥ 50% improvement in the Young Mania Rating Scale (YMRS) total score or a YMRS total score < 12 presented a serum pregnancy test (in cases of women of childbearing potential) consistent with a non-gravid state and used double-barrier contraception throughout the study Exclusion Criteria: relevant electrocardiogram (ECG) or laboratory abnormalities any uncontrolled clinically relevant disorder uninsured capability to comply with the study protocol
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BIA 2-093 1800 mg (Group 1)<br>BIA 2-093 1800 mg once daily (Part II followed a double-blind, parallel-group design in which participants were randomly assigned to treatment with BIA 2-093 300 mg, 900 mg, or 1800 mg once daily). Study medication was administered orally, once daily in the evening. | Drug: BIA 2-093 1800 mg once daily [Group 1 (Part II)]<br>* BIA 2-093 1800 mg taken orally in the evening, for 2 weeks<br>* Other names: Eslicarbazepine acetate;|
| Experimental: BIA 2-093 900 mg (Group 2)<br>BIA 2-093 900 mg once daily (Part II followed a double-blind, parallel-group design in which participants were randomly assigned to treatment with BIA 2-093 300 mg, 900 mg, or 1800 mg once daily). Study medication was administered orally, once daily in the evening. | Drug: BIA 2-093 900 mg once daily [Group 2 (Part II)]<br>* BIA 2-093 900 mg taken orally in the evening, for 2 weeks<br>* Other names: Eslicarbazepine acetate;|
| Experimental: BIA 2-093 300 mg (Group 3)<br>BIA 2-093 300 mg once daily (Part II followed a double-blind, parallel-group design in which participants were randomly assigned to treatment with BIA 2-093 300 mg, 900 mg, or 1800 mg once daily). Study medication was administered orally, once daily in the evening. | Drug: BIA 2-093 300 mg once daily [Group 3 (Part II)]<br>* BIA 2-093 300 mg taken orally in the evening, for 2 weeks.<br>* Other names: Eslicarbazepine acetate;|
| Experimental: ESL (Part I)<br>In Part I, all participants received open-label treatment with BIA 2-093 900 mg once daily for 2 weeks. | Drug: BIA 2-093 900 mg (Part I)<br>* In Part I, patients received one 900 mg BIA 2-093 tablet once daily, taken orally in the evening, for 2 weeks.<br>* Other names: Eslicarbazepine acetate;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Patients Who Showed no Worsening According to the Clinical Global Impression - Bipolar Version (CGI-BP) Scale (Intent-to-Treat Population) | The CGI-BP scale is a modification of the CGI scale, which provides a means of assessing severity and treatment-related improvement in manic and depressive domains reflecting clinically relevant degrees of change. The concept of improvement refers to the clinical distance between the individual's current condition and that prior to the start of treatment. The scale for 'severity of illness' measures mania, depression and overall illness on a 7 point scale from 1 ('normal, not ill') to 7 ('very severely ill'). The scale for 'change from preceding phase' and 'change from worst phase' measures mania, depression, and overall illness on an 8-point scale from 1 (very much improved) to 8 ('not applicable'). If the patient, in 'change from preceding phase', at any visit during the double-blind, has a score of 5, 6, or 7 in any of 3 categories (mania, depression, or overall bipolar illness), then the illness will be considered to have worsened. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bipolar I disorder, Eslicarbazepine acetate, BIA 2-093