A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter, Fixed-Dose Clinical Trial Evaluating The Efficacy, Safety And Tolerability Of Cariprazine In Patients With Bipolar I Depression
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 493
- 试验地点
- 88
- 主要终点
- Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS)
研究概览
简要总结
This study is designed to prospectively confirm the efficacy of a fixed-dose regimen of cariprazine 1.5 milligrams (mg)/day or 3 mg/day compared to placebo for treatment of the depressive episode in participants with bipolar I disorder. The safety and tolerability of the fixed-dose regimens 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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Currently meet the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for bipolar I disorder without psychotic features confirmed by the administration of the Mini International Neuropsychiatric Interview (MINI), with a current major depressive episode of at least 4 weeks and not exceeding 12 months in duration
- •Currently treated as an outpatient at the time of enrollment
- •A verified previous manic or mixed episode. Verification must include one of the following sources:
- •Treatment of mania with an anti-manic agent (eg, lithium or divalproate) or antipsychotic medication with an approved indication for mania
- •Hospital records/Medical records
- •Patient report corroborated by caretaker or previous or current treating clinician
- •17-item Hamilton Depression Rating Scale (HAMD-17) total score ≥ 20
- •HAMD-17 item 1 score ≥ 2
- •CGI-S score ≥ 4
- •Negative serum β-human chorionic gonadotropin (β-hCG) pregnancy test (women of childbearing potential only)
- •Normal physical examination, clinical laboratory test results, and electrocardiogram (ECG) results or abnormal findings that are judged not clinically significant by the Principal Investigator (PI)
排除标准
- •Young Mania Rating Scale (YMRS) total score > 12
- •Four or more episodes of a mood disturbance (depression, mania, hypomania, or mixed state) within the 12 months before Visit 1
- •Any current axis 1 psychiatric diagnosis other than bipolar disorder with the exception of specific phobias
- •History of meeting DSM-5 criteria for:
- •Dementia, amnesic, or other cognitive disorder
- •Schizophrenia, schizoaffective, or other psychotic disorder
- •Mental retardation
- •DSM-5-based diagnosis of borderline or antisocial personality disorder or other axis II disorder of sufficient severity to interfere with participation in this study
- •History of meeting DSM-5 criteria for alcohol or substance abuse or dependence (other than nicotine or caffeine) within the 6 months before Visit 1
- •Positive result on blood alcohol test or urine drug screen for any prohibited medication. Exception:
- •Patients with a positive cannabinoid on entry may be retested before randomization. If the patient remains positive, the patient is no longer eligible
- •Patients positive for opiates on entry, discussion with Study Physician is required.
- •Electroconvulsive therapy in the 3 months before Visit 1
- •Previous lack of response to electroconvulsive therapy
- •Treatment with a depot antipsychotic drug within 1 treatment cycle before Visit 1
- •Treatment with clozapine in a dose of > 50 mg/day in the past 2 years
- •Prior participation in any investigational study of RGH-188 or cariprazine within the past 12 months
- •Previous treatment with vagus nerve stimulation or transcranial magnetic stimulation within 6 months before Visit 1
- •Prior participation with any clinical trials, involving experimental or investigational drugs, within 6 months before Visit 1 or during the study
- •Initiation or termination of psychotherapy for depression within the 3 months preceding Visit 1, or plans to initiate, terminate, or change such therapy during the course of the study.
- •Pregnant, breastfeeding, or planning to become pregnant or breastfeed during the study
- •Gastric bypass or any condition that would be expected to affect drug absorption (lap band procedures are acceptable if there is no problem with absorption)
- •Known history of cataracts or retinal detachment
- •Known human immunodeficiency virus infection
- •Employee, or immediate relative of an employee, of the Sponsor, any of its affiliates or partners, or the study center
研究组 & 干预措施
Cariprazine 3.0 mg
Following a 7 to 14 days screening/washout period, cariprazine 1.5 milligrams (mg) capsule, one per day, orally for 2 weeks increased to cariprazine 3.0 mg capsule, one per day orally beginning on Day 15 for 4 weeks.
干预措施: Cariprazine (Drug)
Cariprazine 1.5 mg
Following a 7 to 14 days screening/washout period, cariprazine 1.5 mg capsule, one per day, orally for 6 weeks.
干预措施: Cariprazine (Drug)
Placebo
Following a 7 to 14 days screening/washout period, matching placebo capsule, one per day, orally for 6 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS)
时间窗: Baseline (Week 0) to Week 6
MADRS is a 10-item, clinician-rated scale that evaluates the participants depressive symptomatology during the past week. Participants were rated on items assessing feelings of sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each of the 10 items was scored on a 7-point scale with a score of 0 reflecting no symptoms and a score of 6 reflecting symptoms of maximum severity for a total possible score of 0 (best) to 60 (worst). A negative change from Baseline indicates improvement. Mixed-effects Model for Repeated Measures (MMRM) with fixed factors (treatment group, pooled study center, and visit), baseline (a covariate), and interactions (treatment group by visit, baseline by visit).
次要结局
- Change From Baseline in Clinical Global Impressions-Severity (CGI-S) Score(Baseline (Week 0) to Week 6)