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)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 404
- 主要终点
- Change From Baseline in Y-MRS Total Score at Day 21
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 10 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Asenapine 2.5 mg twice daily (BID)
Participants receive asenapine 2.5 mg BID for 21 days.
干预措施: asenapine (Drug)
Asenapine 2.5 mg twice daily (BID)
Participants receive asenapine 2.5 mg BID for 21 days.
干预措施: Rescue medication (Drug)
Asenapine 5.0 mg BID
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.
干预措施: asenapine (Drug)
Asenapine 5.0 mg BID
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. Participants receive asenapine 5.0 mg BID for the remainder of the 21-day treatment period.
干预措施: Rescue medication (Drug)
Asenapine 10.0 mg BID
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
干预措施: asenapine (Drug)
Asenapine 10.0 mg BID
Participants receive asenapine 2.5 mg BID through Day 3. On Day 4 participants receive asenapine 2.5 mg in the morning and 5.0 mg in the evening. On Day 5 and 6 participants receive asenapine 5.0 mg BID. On Day 7 participants receive asenapine 5.0 mg in the morning and 10.0 mg in the evening. Participants receive asenapine 10.0 mg BID for the remainder of the 21-day treatment period.
干预措施: Rescue medication (Drug)
Placebo
Participants receive placebo BID for 21 days.
干预措施: Placebo to match asenapine (Drug)
Placebo
Participants receive placebo BID for 21 days.
干预措施: Rescue medication (Drug)
结局指标
主要结局
Change From Baseline in Y-MRS Total Score at Day 21
时间窗: Baseline and Day 21
The Y-MRS is an 11-item clinician-rated instrument for assessing the severity of manic episodes. A severity rating is assigned to each of the 11 items (Elevated mood, Increased motor activity-energy, Sexual interest, Sleep, Irritability, Speech, Language-thought disorder, Thought content, Disruptive-aggressive behavior, Appearance, Insight), based on the participant's subjective report of his or her condition over the previous 48 hours and the clinician's observations during the interview, with the emphasis on the latter. Seven of the 11 items are rated on a scale of 0-4 and 4 of the items are rated on a scale of 0-8, with higher scores indicating greater severity of symptoms. The Y-MRS total score for each participant is the sum of the ratings for the 11 individual items, and can range from 0-60, with higher scores indicating greater severity of symptoms. The reported measure is the change from baseline at Day 21; improvement in symptoms is represented by negative values.
次要结局
- Total Y-MRS 50% Responders at Days 4, 7, 14 and 21(Baseline and Days 4, 7, 14 and 21)
- Change From Baseline in CGI-BP Depression Score at Day 4(Baseline and Day 4)
- Change From Baseline in CGI-BP Depression Score at Day 21(Baseline and Day 21)
- Change From Baseline in CGI-BP Mania Score at Day 21(Baseline and Day 21)
- Change From Baseline in CGI-BP Mania Score at Day 4(Baseline and Day 4)
- Change From Baseline in CGI-BP Mania Score at Day 7(Baseline and Day 7)
- Change From Baseline in Clinical Global Impression Scale for Use in Bipolar Disorder (CGI-BP) Overall Score at Day 21(Baseline and Day 21)
- Change From Baseline in CGI-BP Mania Score at Day 14(Baseline and Day 14)
- Change From Baseline in CDRS-R Total Score at Day 14(Baseline and Day 14)
- Change From Baseline in CDRS-R Total Score at Day 21(Baseline and Day 21)
- Change From Baseline in PQ-LES-Q Overall Score (i.e., Item 15) at Day 21(Baseline and Day 21)
- Change From Baseline in CGI-BP Depression Score at Day 7(Baseline and Day 7)
- Change From Baseline in CGI-BP Depression Score at Day 14(Baseline and Day 14)
- Change From Baseline in Pediatric Quality of Life Enjoyment and Satisfaction Questionnaire (PQ-LES-Q) Total Score at Day 21(Baseline and Day 21)
- Change From Baseline in Children's Depression Rating Scale, Revised (CDRS-R) Total Score at Day 7(Baseline and Day 7)
- Change From Baseline in Children's Global Assessment Scale (CGAS) Score at Day 21(Baseline and Day 21)