Efficacy and Safety of Asenapine Treatment for Pediatric Bipolar Disorder (P06107 Has an Extension [P05898; NCT01349907])(P06107)
Condition: Bipolar Disorder, Pediatric
MeSH terms: Bipolar Disorder
Intervention: asenapine; Placebo to match asenapine; Rescue medication
Intervention description: Asenapine tablets, administered sublingually twice daily at one of three dose levels (2.5 mg, 5.0 mg, or 10.0 mg); Placebo tablets to match asenapine tablets, administered sublingually twice daily; For participants whose symptoms worsen or are not adequately controlled on assigned treatment, rescue medication may be administered during the trial in the following circumstances. For the control of agitation, anxiety, insomnia, restlessness, or akathisia and extrapyramidal symptoms (EPS) some benzodiazepines and EPS medications (i.e., anticholinergics) are allowed. Benadryl (diphenhydramine) and beta blockers are also permitted, provided that they are not taken within 8 hours of efficacy assessments.
Intervention MeSH terms: Asenapine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 404.0
Sex: All
Minimum age: 10 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Bi-polar I disorder; antipsychotic; serotonin; dopamine; noradrenalin; histamine; pediatric

Summary:

      Efficacy and safety of asenapine for the treatment of bipolar I disorder (manic or mixed
      episodes) will be evaluated in participants between 10 and 17 years old, who are either
      hospitalized or non-hospitalized. In this 3-weeks, double-blind, parallel design trial,
      eligible participants will be randomized to receive one out of three fixed dose levels of
      asenapine, or placebo. The study primary hypothesis is that at least one asenapine dose is
      superior to placebo as measured by the change from baseline to Day 21 in Young Mania Rating
      Scale (Y-MRS) total score. Trial medication and placebo are provided as identical-looking
      sublingual tablets; concurrent use of psychotropics is prohibited, except use of short-acting
      benzodiazepines and psychostimulants approved for the treatment of attention deficit
      hyperactivity disorder (ADHD). Main treatment effect is measured using Y-MRS and safety is
      evaluated using the recordings of adverse events, routine blood panels, physical examinations
      (including vital signs), and electrocardiograms. Participants who complete the double blind
      trial may be offered to continue (open-label) treatment with asenapine for an extended period
      of time. Follow-up information on safety parameters will be collected in all participants
      within 30 days following treatment discontinuation.
    

Eligibility criteria:

        Inclusion criteria:

          -  Participants who (or whose parent/legal representative) are able to give written
             informed consent.

          -  Participants must be 10 years of age or older and 17 years of age or younger at the
             time of treatment assignment (randomization).

          -  Participants must have a diagnosis of bipolar I disorder, confirmed by structured
             interview at screening.

          -  Participants must not be pregnant or lactating, and those who are sexually active or
             become sexually active during the trial, and of child-bearing potential, must be using
             a medically accepted form of birth control.

          -  Participants will be required to have stopped taking certain psycho-active medications
             prior to baseline.

          -  Participants must have a caregiver, or other responsible person living with them who
             agrees to provide support to the participant to ensure study and procedure compliance.

        Exclusion criteria:

          -  Diagnosis of bipolar II disorder, or other form of bipolar or psychotic disorder.

          -  Known or suspected mental retardation.

          -  Substance abuse, or dependence, within the past 6 months.

          -  There is risk of self-harm or harm to others.

          -  There is a history of tardive dyskinesia or dystonia.

          -  Pregnancy or lactation during the study.

          -  History of seizure disorder.

          -  Participation in any other clinical trial at the same time.

          -  A family member who is part of the study staff or is directly involved with the study.

          -  Other medical conditions determined by the study staff to possibly interfere with the
             study safety and efficacy evaluations.