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
Study type: Interventional
Phase: Phase 3

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.
    

Detailed description: 
      Participants' Y-MRS total score at baseline will be subtracted from that at the Day 21 visit
      to determine the amount of change over time with treatment. The responses for the 3 different
      asenapine doses compared to placebo will be evaluated. The Y-MRS is an 11 item scale: seven
      items ranked on scale from 0 to 4 and four items ranked 0 to 8 with a range of possible total
      scores from 0 to 60.

      Participants' overall score on the CGI-BP at Day 21 will be evaluated to determine the amount
      of change over time with treatment. The responses for the 3 different asenapine doses
      compared to placebo will be evaluated. CGI-BP overall score is obtained from a single-item
      clinician-rated scale used to assess the participant's overall bipolar illness. Scores range
      from not ill (1) to very severely ill (7).

      The proportion of participants whose total Y-MRS score is decreased ≥50% from baseline at Day
      4, 7, 14 and 21. Results for the 3 different asenapine doses compared to placebo will be
      evaluated.

      Participants' mania sub-score from the CGI-BP will be evaluated for each study visit (Days 4,
      7, 14 and 21) to determine the amount of change over time with treatment. The responses for
      the 3 different asenapine doses compared to placebo will be evaluated.

      Participants' depression sub-score from the CGI-BP will evaluated at each study visit (Days
      4, 7, 14 and 21) to determine the amount of change over time with treatment. The responses
      for the 3 different asenapine doses compared to placebo will be evaluated.

      Participants' CDRS-R at baseline will be subtracted from those at each study visit at which
      this rating was measured (Days 7, 14 and 21) to determine the amount of change over time with
      treatment. The responses for the 3 different asenapine doses compared to placebo will be
      evaluated. The CDRS-R is a 17-item scale that assesses the presence and severity of
      depressive symptoms: fourteen items are rated from 1 to 7 and three items are rated from 1 to
      5; total scores range from 17 to 113.

      Participants' CGAS at baseline will be subtracted from that at the Day 21 visit to determine
      the amount of change over time with treatment. The responses for the 3 different asenapine
      doses compared to placebo will be evaluated. The CGAS is a 100-point scale, with a possible
      range of 1 to 100. Normal social functioning is defined as a CGAS total score of ≥70.

      Participants' PQ-LES-Q total score at baseline will be subtracted from that at the Day 21
      visit to determine the amount of change over time with treatment. The responses for the 3
      different asenapine doses compared to placebo will be evaluated. The PQ-LES-Q is a 15-item
      scale, with total score calculated as the sum of the first 14 items, with a range of 14 to
      70. Each item is scored by the child from 1 to 5, with higher scores indicative of greater
      enjoyment and satisfaction.

      Participants' PQ-LES-Q overall score (i.e. item 15) at baseline will be subtracted from that
      at the Day 21 visit to determine the amount of change over time with treatment. The responses
      for the 3 different asenapine doses compared to placebo will be evaluated. The PQ-LES-Q
      overall score is determined by the answer to item 15 on the questionnaire (range: 1 to 5).
    

Intervention name(s): asenapine; Placebo to match asenapine; Rescue medication
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 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.
Other intervention name(s): SCH 900274, Saphris
Intervention MeSH terms: Asenapine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Bi-polar I disorder; antipsychotic; serotonin; dopamine; noradrenalin; histamine; pediatric