Efficacy and Safety of Eslicarbazepine Acetate (BIA 2-093) in Acute Manic Episodes Associated With Bipolar I Disorder
Condition: Bipolar I Disorder
MeSH terms: Mania
Intervention: Eslicarbazepine Acetate; Eslicarbazepine Acetate; Placebo
Intervention description: Eslicarbazepine Acetate, starting with 800 mg per day and up-titrated in 800 mg steps until 2400 mg (maximum dose) according to clinical response.; Eslicarbazepine Acetate, starting with 600 mg per day and up-titrated in 600 mg steps until 1800 mg (maximum dose) according to clinical response.; Placebo
Intervention MeSH terms: Eslicarbazepine acetate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 161.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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
    

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 bipolar disorder preventive medication (for carbamazepine or
             oxcarbazepine see exclusion criteria), antidepressants, antipsychotic, anxiolytic,
             antiparkinsonian, and/or other potentially centrally acting drugs had to be washed-out
             for at least 2 days prior to randomisation (V2, Day 1).

          -  Patients treated with lithium or valproate could only be randomised with plasma levels
             < 0.5 mmol/L and < 50 mg/L, respectively.