Clinical trial NCT01244815: Efficacy and Safety of Asenapine Treatment for Pediatric Bipolar Disorder (P06107 Has an Extension [P05898; NCT01349907])(P06107)
Official title: Efficacy and Safety of 3-Week Fixed-Dose Asenapine Treatment in Pediatric Acute Manic or Mixed Episodes Associated With Bipolar I Disorder (Protocol No. P06107)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Bipolar Disorder, Pediatric
Keywords: Bi-polar I disorder
antipsychotic
serotonin
dopamine
noradrenalin
histamine
pediatric
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
First posted: 2010-11-19
Enrollment: 404
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

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.

Primary outcomes:
measure: Change From Baseline in Y-MRS Total Score at Day 21
timeFrame: Baseline and Day 21
Secondary outcomes:
measure: Change From Baseline in Clinical Global Impression Scale for Use in Bipolar Disorder (CGI-BP) Overall Score at Day 21
timeFrame: Baseline and Day 21
measure: Total Y-MRS 50% Responders at Days 4, 7, 14 and 21
timeFrame: Baseline and Days 4, 7, 14 and 21
measure: Change From Baseline in CGI-BP Mania Score at Day 4
timeFrame: Baseline and Day 4
measure: Change From Baseline in CGI-BP Mania Score at Day 7
timeFrame: Baseline and Day 7
measure: Change From Baseline in CGI-BP Mania Score at Day 14
timeFrame: Baseline and Day 14
measure: Change From Baseline in CGI-BP Mania Score at Day 21
timeFrame: Baseline and Day 21
measure: Change From Baseline in CGI-BP Depression Score at Day 4
timeFrame: Baseline and Day 4
measure: Change From Baseline in CGI-BP Depression Score at Day 7
timeFrame: Baseline and Day 7
measure: Change From Baseline in CGI-BP Depression Score at Day 14
timeFrame: Baseline and Day 14
measure: Change From Baseline in CGI-BP Depression Score at Day 21
timeFrame: Baseline and Day 21
measure: Change From Baseline in Children's Depression Rating Scale, Revised (CDRS-R) Total Score at Day 7
timeFrame: Baseline and Day 7
measure: Change From Baseline in CDRS-R Total Score at Day 14
timeFrame: Baseline and Day 14
measure: Change From Baseline in CDRS-R Total Score at Day 21
timeFrame: Baseline and Day 21
measure: Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Day 21
timeFrame: Baseline and Day 21
measure: Change From Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score at Day 21
timeFrame: Baseline and Day 21
measure: Change From Baseline in PQ-LES-Q Overall Score (i.e., Item 15) at Day 21
timeFrame: Baseline and Day 21
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Findling RL, Landbloom RL, Szegedi A, Koppenhaver J, Braat S, Zhu Q, Mackle M, Chang K, Mathews M. Asenapine for the Acute Treatment of Pediatric Manic or Mixed Episode of Bipolar I Disorder. J Am Acad Child Adolesc Psychiatry. 2015 Dec;54(12):1032-41. doi: 10.1016/j.jaac.2015.09.007. Epub 2015 Oct 24.