Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) in Acute Manic Episodes Associated With Bipolar I Disorder

NCT ID: NCT01822678

Last Updated: 2014-03-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 161 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-31
• Study Completion Date: 2006-11-30

Brief Summary

Multicentre, double-blind, randomised, parallel-group, placebo-controlled dose-titration study; depending on clinical efficacy, up-titration of dosage 3 and 6 days after start of treatment; maintenance of individual maximum dose for the rest of the total 3-week treatment period; subsequently, down-titration (according to the dose steps and the time intervals of up-titration) and administration of an established anti-manic therapy during the tapering-off period (in patients who discontinued treatment) or entry into a recurrence prevention study (Protocol PRA+SCO/BIA-2093-205; reported under separate cover) as an option for patients who responded to the study treatment

Detailed Description

Objectives:

The primary objective was to evaluate the dose-dependent efficacy of 2 dose-titration regimens of Eslicarbazepine Acetate (ESL) compared with placebo as therapy in patients with acute mania.

The secondary objective was to evaluate the safety and tolerability of 2 dose-titration regimens of Eslicarbazepine Acetate in comparison to placebo.

Conditions

Bipolar I Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group 1

Group 1: Eslicarbazepine Acetate, starting with 800 mg per day and up-titrated in 800 mg steps until 2400 mg (maximum dose) according to clinical response.

Group Type: EXPERIMENTAL

Eslicarbazepine Acetate

Intervention Type: DRUG

Eslicarbazepine Acetate, starting with 800 mg per day and up-titrated in 800 mg steps until 2400 mg (maximum dose) according to clinical response.

Group 2

Group 2: Eslicarbazepine Acetate, starting with 600 mg per day and up-titrated in 600 mg steps until 1800 mg (maximum dose) according to clinical response.

Group Type: EXPERIMENTAL

Eslicarbazepine Acetate

Intervention Type: DRUG

Eslicarbazepine Acetate, starting with 600 mg per day and up-titrated in 600 mg steps until 1800 mg (maximum dose) according to clinical response.

Group 3

Group 3: Placebo (change in daily number of tablets administered, according to clinical response).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Eslicarbazepine Acetate

Eslicarbazepine Acetate, starting with 800 mg per day and up-titrated in 800 mg steps until 2400 mg (maximum dose) according to clinical response.

Intervention Type: DRUG

Eslicarbazepine Acetate

Eslicarbazepine Acetate, starting with 600 mg per day and up-titrated in 600 mg steps until 1800 mg (maximum dose) according to clinical response.

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

Eslicarbazepine Acetate tablets; Eslicarbazepine Acetate tablets; sugar pill

Eligibility Criteria

Inclusion Criteria

• aged ≥18 years;
• a documented diagnosis of bipolar I disorder according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) criteria (i.e., 296.0, 296.4 or 296.6) [8];
• currently displaying an acute manic (including mixed) episode according to the DSM-IV criteria;
• a Young Mania Rating Scale (YMRS) total score of ≥20;
• symptoms of the current manic episode starting within 2 weeks prior to randomisation (V2, Day 1);
• able to undergo a standard evaluation, including clinical interview, ratings and laboratory studies;
• signed informed consent form;
• post-menopausal or otherwise incapable of becoming pregnant by reason of surgery or tubal ligation; women of childbearing potential had to present a serum pregnancy test consistent with a non-gravid state and had to use double-barrier contraception until the post-study visit (PSV).

Exclusion Criteria

• a history of schizophrenia or schizoaffective disorder, psychotic features or rapid cycling;
• currently treated with carbamazepine or oxcarbazepine;
• a history of unresponsiveness, intolerance or hypersensitivity to related compounds (carbamazepine, oxcarbazepine or licarbazepine);
• use of any depot-neuroleptics for the current manic episode;
• abuse of stimulating drugs or use of any systemic sympathicomimetic drug within the previous 2 weeks;
• electroconvulsive therapy within the previous 3 months;
• a history of dependence or chronic abuse from alcohol, drugs or medications within the last year;
• judged clinically to be at risk of harm to self or others;
• second or third-degree atrioventricular blockade not corrected with a pacemaker;
• relevant electrocardiogram (ECG) or laboratory abnormalities;
• calculated creatinine clearance <30 mL/min [men: (140-age) x weight / serum creatinine x 72; women: (0.85) (140-age) x weight / serum creatinine x 72. Age in years, weight in kg, and serum creatinine in mg/dL];
• pregnant or nursing;
• participating in another drug clinical trial within the last 2 months before the randomisation visit;
• not ensured capability to perform the trial or to comply with the study protocol (e.g., mental retardation or severe inability to communicate);
• any other uncontrolled clinically relevant disorder;
• previous treatment with Eslicarbazepine Acetate;
• a history or presence of bone marrow impairment or depression (introduced by protocol amendment No. 1);
• a history or presence of acute intermittent porphyria (introduced by protocol amendment No. 1).

Patients receiving treatment for bipolar disorder or other central nervous system disorders at randomisation were excluded from randomisation. If the patients had previously used such medications the following restrictions had to be taken into account:

• Patients treated with lithium or valproate could only be randomised with plasma levels < 0.5 mmol/L and < 50 mg/L, respectively.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bial - Portela C S.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrício Soares-da-Silva, MD, PhD

Role: STUDY_DIRECTOR

BIAL - Portela & Ca. SA

Other Identifiers

BIA-2093-203

Identifier Type: -

Identifier Source: org_study_id