A Study to Evaluate the Effectiveness and Safety of Extended-Release (ER) Paliperidone Compared With Placebo in Delaying the Recurrence of Symptoms in Bipolar I Disorder
Condition: Bipolar Disorder
MeSH terms: Bipolar Disorder
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to evaluate the effectiveness and safety of oral
      extended-release (ER) paliperidone compared with placebo in the prevention of the recurrence
      of mood symptoms in patients with Bipolar I Disorder who initially respond to treatment of an
      acute manic or mixed episode with paliperidone ER. Olanzapine was included as an active
      control arm, although the study is not designed to allow for a direct comparison of
      olanzapine with paliperidone.
    

Detailed description: 
      This is a randomized (patients are assigned different treatments based on chance),
      double-blind (neither the patient nor the physician knows whether drug or placebo is being
      taken), active- and placebo-controlled, parallel-group, multicenter study to evaluate the
      efficacy (effectiveness) and safety of paliperidone ER relative to placebo in the prevention
      of recurrent mood symptoms associated with Bipolar I Disorder.

      There are 5 phases in this study: a screening phase (lasting up to 7 days) to establish a
      subject's eligibility for the study,; a 3-week double-blind acute treatment phase to treat
      the acute or manic episode; a 12-week double-blind treatment continuation phase to establish
      a patient's clinical stability,; a double-blind treatment maintenance phase to measure the
      time to symptom recurrence that will last until the patient experiences a recurrence,; and a
      follow-up phase consisting of a visit approximately 1 week after the last study visit. All
      antipsychotic drugs and all mood stabilizers other than study drug must be discontinued
      before the first study drug administration.

      Hospitalization is required for at least the first 7 days of the acute treatment phase. At
      the beginning of the acute treatment phase, patients will be randomly assigned to receive ER
      paliperidone or olanzapine in a 4:1 ratio. Patients in the ER paliperidone group who have a
      clinical response at the end of the acute treatment phase, remain clinically stable
      throughout the continuation phase, and achieve remission for each of the last 3 weeks of the
      continuation phase will again be randomly assigned: they will be assigned in a 1:1 ratio to
      receive ER paliperidone or placebo in the maintenance phase. Patients in the olanzapine
      treatment group who fulfill the same criteria will continue receiving double-blind treatment
      with olanzapine in the maintenance phase.

      Measures of efficacy used are the Young Mania Rating Scale (YMRS), Montgomery-Åsberg
      Depression Rating Scale (MADRS), Clinical Global Impression - Bipolar Disorder - Severity of
      Illness Scale (CGI-BP-S), Global Assessment of Functioning (GAF), the Short Form-36 to
      measure health-related functional status, and the sleep visual analog scale (VAS).

      Safety evaluations include monitoring of adverse events, clinical laboratory tests (including
      urine pregnancy testing and hemoglobin A1c), 12-lead ECG, vital signs measurements,
      measurement of orthostatic changes in pulse and blood pressure, physical examinations
      (including height, body weight, and waist circumference), and monitoring of extrapyramidal
      symptoms using the Abnormal Involuntary Movement Scale (AIMS), the Barnes Akathisia Rating
      Scale (BARS), and the Simpson Angus Scale (SAS). In addition, the Scale for Suicidal Ideation
      will be administered to assess suicidality.

      The primary hypothesis for this study is that, during the long-term treatment of patients
      with Bipolar I Disorder who maintain clinical stability after an acute manic or mixed
      episode, ER paliperidone is superior to placebo in delaying the time to recurrence of any
      mood symptoms associated with Bipolar I Disorder. Patients begin the acute treatment phase at
      6.0 mg/day of oral ER paliperidone or 10 mg/day of oral olanzapine. Dosages may be adjusted,
      as needed, between 3 to 12 mg/day of ER paliperidone or 5 to 20 mg/day of olanzapine, through
      the end of the continuation phase. Then, in the maintenance phase, patients receive the
      dosage of ER paliperidone (or ER paliperidone placebo) or olanzapine reached at the end of
      the continuation phase. They remain on those dosages until the end of the study.
    

Intervention name(s): Olanzapine; Paliperidone ER; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Once daily in dose range of 5 to 20 mg/day for 15 weeks, then until recurrence; Once daily in dose range of 3 to 12 mg/day for 15 weeks, then until recurrence; Once daily until recurrence (only after initial 15 weeks on paliperidone ER)
Intervention MeSH terms: Olanzapine; Paliperidone Palmitate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Bipolar Disorder; Mania; Depression; Manic-Depressive Disorder