Efficacy and Safety of Asenapine Treatment for Pediatric Bipolar Disorder {P06107 Has an Extension (P05898; NCT01349907)}(P06107 AM4)
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Purpose
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, patients eligible for participation will be randomized to receive one out of three fixed dose levels of asenapine, or placebo. 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 the Young Mania Rating Scale (Y-MRS) and safety is evaluated using the recordings of adverse events, routine blood panels, physical examinations (including vital signs), and electrocardiograms. Patients 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 patients within 30 days following treatment discontinuation.
| Condition | Intervention | Phase |
|---|---|---|
|
Bipolar Disorder, Pediatric |
Drug: asenapine Drug: Placebo to match asenapine Drug: Rescue medication |
Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
| 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) |
- Change from baseline in the Young-Mania Rating Scale (YMRS) total score at Day 21 [ Time Frame: Baseline and Day 21 ] [ Designated as safety issue: No ]
- Change from baseline in Clinical Global Impression Scale for use in Bipolar Disorder (CGI-BP) overall score at Day 21 [ Time Frame: Baseline and Day 21 ] [ Designated as safety issue: No ]
- Proportion of Y-MRS ≥50% responders at all post baseline visits [ Time Frame: Baseline and Days 4, 7, 14 and 21 ] [ Designated as safety issue: No ]
- Dose-response relationship for Day 21 change from baseline in the Y-MRS total score [ Time Frame: Baseline and Day 21 ] [ Designated as safety issue: No ]
- Change from baseline in CGI-BP mania score at all post baseline visits [ Time Frame: Baseline and Days 4, 7, 14 and 21 ] [ Designated as safety issue: No ]
- Change from baseline in CGI-BP depression score at all post baseline visits [ Time Frame: Baseline and Days 4, 7, 14 and 21 ] [ Designated as safety issue: No ]
- Change from baseline in Children's Depression Rating Scale, Revised (CDRS-R) total score at Days 7, 14 and 21 [ Time Frame: Baseline and Days 7, 14 and 21 ] [ Designated as safety issue: No ]
- Change from baseline in Children's Global Assessment Scale (CGAS) total score at Day 21 [ Time Frame: Baseline and Day 21 ] [ Designated as safety issue: No ]
- Change from baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) total score at Day 21 [ Time Frame: Baseline and Day 21 ] [ Designated as safety issue: No ]
- Change from baseline in PQ-LES-Q overall score (i.e., item 15) at Day 21 [ Time Frame: Baseline and Day 21 ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 400 |
| Study Start Date: | June 2011 |
| Estimated Study Completion Date: | August 2013 |
| Estimated Primary Completion Date: | July 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Asenapine 2.5 mg twice daily (BID)
Asenapine 2.5 mg administered twice daily
|
Drug: asenapine
Asenapine tablets, administered orally twice daily at one of three dose levels (2.5 mg, 5 mg, or 10 mg)
Other Name: SCH 900274, Saphris
Drug: Rescue medication
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.
|
|
Experimental: Asenapine 5 mg BID
Asenapine 5 mg administered twice daily
|
Drug: asenapine
Asenapine tablets, administered orally twice daily at one of three dose levels (2.5 mg, 5 mg, or 10 mg)
Other Name: SCH 900274, Saphris
Drug: Rescue medication
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.
|
|
Experimental: Asenapine 10 mg BID
Asenapine 10 mg administered twice daily
|
Drug: asenapine
Asenapine tablets, administered orally twice daily at one of three dose levels (2.5 mg, 5 mg, or 10 mg)
Other Name: SCH 900274, Saphris
Drug: Rescue medication
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.
|
|
Placebo Comparator: Placebo
Placebo, administered twice daily
|
Drug: Placebo to match asenapine
Placebo tablets to match asenapine tablets at one of three dose levels (2.5 mg, 5 mg, or 10 mg), administered orally twice daily
Drug: Rescue medication
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.
|
Detailed Description:
Participants' scores on the Y-MRS at baseline will be subtracted from those at Day 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 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 is a single-item clinician-rated scale used to assess the participant's global improvement compared to their status at baseline. 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.
The change from baseline at Day 21 in the Y-MRS total score will be compared among the asenapine dose groups, and for each dose relative to placebo.
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 severity and presence 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| Ages Eligible for Study: | 10 Years to 17 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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 be unsafe for study participation.
Contacts and Locations| Contact: Toll Free Number | 1-888-577-8839 |
Show 69 Study Locations More Information
No publications provided
| Responsible Party: | Merck |
| ClinicalTrials.gov Identifier: | NCT01244815 History of Changes |
| Other Study ID Numbers: | P06107 |
| Study First Received: | November 18, 2010 |
| Last Updated: | May 22, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Merck:
|
Bi-polar I disorder antipsychotic serotonin dopamine |
noradrenalin histamine pediatric |
Additional relevant MeSH terms:
|
Bipolar Disorder Affective Disorders, Psychotic Mood Disorders Mental Disorders Asenapine Antipsychotic Agents Tranquilizing Agents |
Central Nervous System Depressants Physiological Effects of Drugs Pharmacologic Actions Central Nervous System Agents Therapeutic Uses Psychotropic Drugs |
ClinicalTrials.gov processed this record on May 22, 2013