A Phase 2, Multicenter, Randomized, Double-blind, Placebo Controlled Study of the Safety and Efficacy of OPC-34712 as Adjunctive Therapy in the Treatment of Adult Attention Deficit/ Hyperactivity Disorder
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 740
- 主要终点
- Mean Change From Baseline (End of Phase A) in the CAARS-O:SV ADHD Symptoms Total Score (18 Items) to End of Phase B
研究概览
简要总结
This study tests the effects of an investigational antipsychotic drug (called OPC-34712) in adults with attention deficit hyperactivity disorder (ADHD) when taken with an approved stimulant medication to explore a possible impact on sleep, quality of life and cognitive function.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female outpatients 18 to 55 years of age, inclusive, at the time of informed consent.
- •Participants with a primary diagnostic and statistical manual of mental disorders, fourth edition, text revision (DSM-IV-TR) diagnosis of ADHD (including inattentive, hyperactive, and combined subtypes) as confirmed by the Conners' Adult ADHD diagnostic interview (CAADID). Participants may have received prior treatment for adult ADHD, may be currently receiving treatment for adult ADHD at screening, or may be treatment-naive.
- •Participants willing to discontinue all prohibited psychotropic medication starting from the time of signing the informed consent and during the study period.
排除标准
- •Females who are breast-feeding and/or who have a positive pregnancy test result prior to receiving study drug.
- •Participants with an adequate response, as determined by the investigator, to any stimulant taken for the treatment of adult ADHD after 18 years of age.
- •Participants with a clinically significant current Axis II (DSM-IV-TR) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal, or histrionic personality disorder.
- •Participants who participated in a clinical trial within the last 180 days or who participated in more than two clinical trials within the past year.
研究组 & 干预措施
Phase A (Single-blind Prospective Treatment Phase): Placebo + Stimulant
Participants received single-blind matching-placebo tablets along with open-label stimulant determined by the investigator, once daily for 5 weeks. Once assigned to a stimulant by the investigator, participants remained on the same stimulant for the duration of the trial. Participants who met eligibility criteria i.e., who received prior treatment for adult ADHD and treatment-naïve participants were included in this arm group. Participants with incomplete response at the end of Phase A (Week 5) entered Phase B and rest of the participants continued to Phase A+.
干预措施: Placebo (Drug)
Phase A (Single-blind Prospective Treatment Phase): Placebo + Stimulant
Participants received single-blind matching-placebo tablets along with open-label stimulant determined by the investigator, once daily for 5 weeks. Once assigned to a stimulant by the investigator, participants remained on the same stimulant for the duration of the trial. Participants who met eligibility criteria i.e., who received prior treatment for adult ADHD and treatment-naïve participants were included in this arm group. Participants with incomplete response at the end of Phase A (Week 5) entered Phase B and rest of the participants continued to Phase A+.
干预措施: Stimulant Therapy (Drug)
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
Participants with incomplete response (with a > 0% and < 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment { Week 5} as measured by the CAARS-O:SV { Conners' Adult ADHD Rating Scale-Observer: Screening Version}, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a clinical global impression - improvement scale (CGI-I) score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 milligram (mg) tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
干预措施: OPDC-34712 (Drug)
Phase B (Double-blind Randomization Phase): Brexpiprazole + Stimulant
Participants with incomplete response (with a > 0% and < 30% reduction in ADHD Symptoms Total Score {18 items} between the baseline of Phase A and the end of prospective treatment { Week 5} as measured by the CAARS-O:SV { Conners' Adult ADHD Rating Scale-Observer: Screening Version}, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a clinical global impression - improvement scale (CGI-I) score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received Brexpiprazole 2 milligram (mg) tablet along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
干预措施: Stimulant Therapy (Drug)
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
Participants with incomplete response (with a > 0% and < 30% reduction in ADHD Symptoms Total Score {18 items} between the Baseline of Phase A and the end of prospective treatment { Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
干预措施: Placebo (Drug)
Phase B (Double-blind Randomization Phase): Placebo + Stimulant
Participants with incomplete response (with a > 0% and < 30% reduction in ADHD Symptoms Total Score {18 items} between the Baseline of Phase A and the end of prospective treatment { Week 5} as measured by the CAARS-O:SV, and a CAARS-O:SV ADHD Symptoms Total Score {18 items} of ≥ 24 at Week 5, and a CGI-I score of 3 or 4 at Week 5) at the end of Phase A (Week 5), received matching-placebo tablets along with stimulant determined by the investigator, once daily for 6 weeks (up to Week 11).
干预措施: Stimulant Therapy (Drug)
Phase A+ (Single-blind Phase A Responders and Non-responders): Placebo + Stimulant
Participants with response (with a ≥ 30% reduction in ADHD Symptoms Total Score {18 items} between Baseline of Phase A and the end of prospective treatment { Week 5} as measured by the CAARS-O:SV, or a CAARS-O:SV ADHD Symptoms Total Score {18 items} of < 24 at Week 5, or a CGI-I score of < 3 at Week 5) and non-response (with deterioration or no change in ADHD symptoms at Week 5) at the end of Phase A (Week 5), received single-blind matching-placebo tablets along with open-label stimulant determined by the investigator, once daily for an additional 6 weeks (up to Week 11).
干预措施: Placebo (Drug)
Phase A+ (Single-blind Phase A Responders and Non-responders): Placebo + Stimulant
Participants with response (with a ≥ 30% reduction in ADHD Symptoms Total Score {18 items} between Baseline of Phase A and the end of prospective treatment { Week 5} as measured by the CAARS-O:SV, or a CAARS-O:SV ADHD Symptoms Total Score {18 items} of < 24 at Week 5, or a CGI-I score of < 3 at Week 5) and non-response (with deterioration or no change in ADHD symptoms at Week 5) at the end of Phase A (Week 5), received single-blind matching-placebo tablets along with open-label stimulant determined by the investigator, once daily for an additional 6 weeks (up to Week 11).
干预措施: Stimulant Therapy (Drug)
结局指标
主要结局
Mean Change From Baseline (End of Phase A) in the CAARS-O:SV ADHD Symptoms Total Score (18 Items) to End of Phase B
时间窗: Baseline [end of Phase A (Week 5)] to Week 11
The CAARS-O:SV is a 30 items scale with 3 subscales: Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Inattentive Symptoms (9 items), DSM- IV Hyperactive/Impulsive Symptoms (9 items), and DSM-IV ADHD Index (12 items). Total ADHD Symptoms Score (18 items) consisted of the combined score for the inattentive symptoms and hyperactive/impulsive symptoms subscales and is scored on a 4-point scale from 0 (not at all; never) to 3 (very much, very frequently) for a total score ranging from of 0 to 54, higher scores indicate worsening of symptoms. A negative change from Baseline indicates improvement. The Mixed model repeated measures (MMRM) model was used for analysis.
次要结局
- Change From Baseline (End of Phase A) in Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) Total Score to End of Phase B(Baseline [end of Phase A (Week 5)] to Week 11)
- Change From Baseline (End of Phase A) in the Spatial Working Memory (SWM) Between Errors 4-8 Boxes Test Score as Measured by Cambridge Neuropsychological Test Automated Battery (CANTAB) to End of Phase B(Baseline [end of Phase A (Week 5)] to Week 11)
- Change From Baseline (End of Phase A) in CAARS-O:SV Inattentive Symptoms Subscale Score (9 Items) to Each Time Point in Phase B(Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11)
- Change From Baseline (End of Phase A) in Sleep Improvement Measured by Insomnia Severity Index (ISI) Total Score to End of Phase B(Baseline [end of Phase A (Week 5)] to Week 11)
- Change From Baseline (End of Phase A) in CAARS-O:SV ADHD Symptoms Total Score (18 Items) to Each Time Point in Phase B Other Than Week 11(Baseline [end of Phase A (Week 5)] to Weeks 6, 7, 8, 9 and 10)
- Change From Baseline (End of Phase A) in CAARS-O:SV Hyperactive/Impulsive Symptoms Subscale Score (9 Items) to Each Time Point in Phase B(Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11)
- Change From Baseline (End of Phase A) in CAARS-O:SV ADHD Index Score (12 Items) to Each Time Point in Phase B(Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11)
- Change From Baseline (End of Phase A) to Weeks 7 and 9 in ISI Total Score(Baseline [end of Phase A (Week 5)]; Weeks 7 and 9)
- Percentage of Participants With Categorical Change in Sleep Improvement Measured by Individual Scores for Items 1, 2, and 3 of the ISI at End of Phase B(Baseline [(end of Phase A (Week 5)] to Weeks 7, 9 and 11)
- Change From Baseline (End of Phase A) in Conners' Adult ADHD Rating Scale-Self-Report: Screening Version (CAARS-S:SV) ADHD Symptoms Total Score (18 Items) to Each Timepoint in Phase B(Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11)
- Change From Baseline (End of Phase A) in CAARS-S:SV Inattentive Symptoms Subscale Score (9 Items) to Each Timepoint in Phase B(Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11)
- Change From Baseline (End of Phase A) in Sleep Improvement Measured by ISI for Item 2 Score (Difficulty Staying Asleep) to End of Phase B(Baseline [end of Phase A (Week 5)] to Week 11)
- Change From Baseline (End of Phase A) in CAARS-S:SV Hyperactive/Impulsive Symptoms Subscale Score (9 Items) to Each Timepoint in Phase B(Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11)
- Change From Baseline (End of Phase A) in CAARS-S:SV ADHD Index Score (12 Items) to Each Timepoint in Phase B(Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11)
- Change From Baseline (End of Phase A) in Clinical Global Impression - Severity of Illness Scale (CGI-S) Score to Each Timepoint in Phase B(Baseline [end of Phase A (Week 5)]; Weeks 6, 7, 8, 9, 10 and 11)
- Change From Baseline (End of Phase A) in the SWM Strategy 6-8 Boxes Test Score as Measured by CANTAB to End of Phase B(Baseline [end of Phase A (Week 5)] to Week 11)
- Change From Baseline (End of Phase A) in the SWM Within Errors 4-8 Boxes Test Score as Measured by CANTAB to End of Phase B(Baseline [end of Phase A (Week 5)] to Week 11)
- Change From Baseline (End of Phase A) in the Rapid Visual Information Processing (RVP) A Prime Test Score as Measured by CANTAB to End of Phase B(Baseline [end of Phase A (Week 5)] to Week 11)
- Change From Baseline (End of Phase A) in the RVP Median Response Latency Score as Measured by CANTAB to End of Phase B(Baseline [end of Phase A (Week 5)] to Week 11)
- Change From Baseline (End of Phase A) in RVP Total False Alarms Score as Measured by CANTAB to End of Phase B(Baseline [end of Phase A (Week 5)] to Week 11)
- Change From Baseline (End of Phase A) in the Stop Signal Task (SST) Stop Signal Reaction Time (SSRT) Score as Measured by CANTAB to End of Phase B(Baseline [end of Phase A (Week 5)] to Week 11)
- Change From Baseline (End of Phase A) in the SST Proportion of Successful Stops Score as Measured by CANTAB to End of Phase B(Baseline [end of Phase A (Week 5)] to Week 11)
- Change From Baseline (End of Phase A) in SST Median Reaction Time Score on Go Trials as Measured by CANTAB to End of Phase B(Baseline [end of Phase A (Week 5)] to Week 11)
- Change From Baseline (End of Phase A) in WRAADDS Attention + Organization Subscale Score to End of Phase B(Baseline [end of Phase A (Week 5)] to Week 11)
- Change From End of Phase A (Week 5 Visit) to End of Phase B (Week 11 Visit) in WRAADDS Hyperactivity + Impulsivity Subscale Score to End of Phase B(Baseline [end of Phase A (Week 5)] to Week 11)
- Change From Baseline (End of Phase A) in WRAADDS Temper + Mood Lability + Emotional Over-reactivity Subscale Score to End of Phase B(Baseline [end of Phase A (Week 5)] to Week 11)
- Mean CGI-I Score at Each Timepoint in Phase B(Weeks 6, 7, 8, 9, 10 and 11)
- Percentage of Participants With CAARS-O:SV ADHD Symptoms Response Rate in Phase B(Weeks 6, 7, 8, 9, 10 and 11)
- Percentage of Participants With CAARS-O:SV ADHD Symptoms Remission Rate in Phase B(Weeks 6, 7, 8, 9, 10 and 11)
- Percentage of Participants With CAARS-S:SV ADHD Symptoms Response Rate in Phase B(Weeks 6, 7, 8, 9, 10 and 11)
- Percentage of Participants With CAARS-S:SV ADHD Symptoms Remission Rate in Phase B(Weeks 6, 7, 8, 9, 10 and 11)
- Percentage of Participants With CGI-I Response Rate in Phase B(Weeks 6, 7, 8, 9, 10 and 11)