A Study to Evaluate the Efficacy and Safety of Three Fixed Doses of Extended-release Paliperidone in Subjects With Bipolar I Disorder
Condition: Bipolar Disorder; Mood Disorders
MeSH terms: Bipolar Disorder; Mood Disorders
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to evaluate the effectiveness and safety of 3 different doses of
      paliperidone extended release (ER) compared to placebo in patients diagnosed with Bipolar I
      Disorder who are experiencing an acute manic or mixed episode. This study will also evaluate
      the effects of paliperidone extended release on global functioning, and the relationship
      between blood levels and the effectiveness and safety of paliperidone.
    

Detailed description: 
      Several treatments are available for the treatment of acute manic and mixed episodes
      associated with bipolar disorder. Some of these treatments although used for many years, are
      associated with well-known problems such as poor tolerability, significant toxicities, narrow
      therapeutic ranges, and drug interactions. Often, several drugs must be used in combination
      to achieve the best clinical effect. More recently, a group of compounds known as atypical
      antipsychotics, such as risperidone, have been licensed for use in this indication. Based on
      the pharmacological profile of Paliperidone, it is expected to be effective in the treatment
      of acute manic and mixed episodes associated with bipolar disorder. Paliperidone extended
      release has been shown to be effective in schizophrenia and it has an improved drug delivery
      system with a reduced potential for drug interactions. Study drug tablets are designed to
      deliver the appropriate amount of drug (3 mg or 6 mg) using a "Push-Pull" delivery system
      based on a patented oral osmotic pump technology (OROS) that allows the drug to be delivered
      at a relatively controlled rate for 24 hours. This study will test 3 different doses of
      paliperidone extended release (3, 6, or 12 mg/day once daily) compared to placebo (inactive
      substance). There are 3 parts to the study: a screening and washout phase that lasts up to 7
      days to determine if patients are eligible for the study and to discontinue all current
      medications, a double-blind treatment phase that lasts for 3 weeks, and a follow-up phase
      that lasts about 1 week after the end-of-study visit or early withdrawal from the study.
      During the double-blind treatment phase, patients are randomly assigned to receive treatment
      either with placebo or 1 of 3 daily doses of paliperidone extended release. Patients assigned
      to paliperidone extended release will receive either 3, 6, or 12 mg/day given once daily for
      a 3-week period. All patients whether receiving paliperidone extended release or placebo will
      take 2 capsules each time the study drug is given. Patients will be hospitalized for at least
      the first 7 days of double-blind treatment, and may be discharged on the seventh day and
      followed as outpatients based on the judgment of the study doctor. End-of-study/early
      withdrawal procedures will be done after the last dose of study drug has been received and
      blood samples have been taken, or at early withdrawal from the study. Patients will have a
      follow-up visit with safety evaluations approximately 1 week later. The study, including the
      screening and washout phases, will last approximately 35 days or 5 weeks. Effectiveness will
      be primarily determined by the change in the total Young Mania Rating Scale (YMRS) score from
      the beginning (baseline) to the end of the double-blind treatment phase of the study. The
      Young Mania Rating Scale is an 11-item established measure used to evaluate manic symptoms. A
      secondary measure of effectiveness is the change in the Global Assessment of Functioning
      Scale (GAF) from baseline to the end of the double-blind treatment phase of the study. Other
      measures of effectiveness include the time to onset of therapeutic effect, responder rate
      (defined as 50% or more reduction from baseline in Young Mania Rating Scale score), and
      changes from baseline to the end of the double-blind treatments phase in all other assessment
      scales. Additional assessment scales will be used to evaluate the clinical progress of the
      patient, psychotic and depressive symptoms in bipolar disorder, quality of sleep and daytime
      drowsiness, health-related function, and rate the severity of the patient's bipolar disorder.
      Safety will be evaluated by the frequency, severity, and timing of side effects, clinical
      laboratory tests (including pregnancy tests), 12-lead electrocardiograms (ECGs), vital signs
      measurements, and physical and neurological examinations. The study hypotheses for the
      primary and secondary effectiveness measures are 1) that at least 1 dose of paliperidone
      extended release is better than placebo on the change from baseline in the Young Mania Rating
      Scale total score at the end of 3 weeks of treatment, and 2) at least 1 dose of paliperidone
      extended release is better than placebo on the change from baseline in Global Assessment of
      Functional Scale score at the end of 3 weeks of treatment. The potential effect of the
      variation in genes related to paliperidone ER may be evaluated separately in patients who
      consent to DNA (deoxyribonucleic acid) testing. Paliperidone ER, 3, 6, or 12 mg/day or
      placebo once daily for 3 weeks. To maintain the blind, all patients will take 2 capsules each
      time study drug is given. Capsules may contain a 3-mg tablet and matching placebo, a 6-mg
      tablet and matching placebo, two 6-mg tablets, or placebo (inactive) tablets. The doses of
      study drug will be fixed throughout the study.
    

Intervention name(s): Paliperidone extended-release
Intervention type(s): Drug
Intervention MeSH terms: Paliperidone Palmitate
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Treatment
Keywords: Affective psychosis; mixed-state; bipolar disorder; manic disorder; manic-depressive; psychosis; mania; manic state; paliperidone; paliperidone ER.