A Phase 1, Two-part, Open-label, Randomized, Exploratory and Single Ascending Dose, Parallel Arm Trial to Determine the Pharmacokinetics, Safety, and Tolerability of Brexpiprazole Long-acting Injectable Administered Subcutaneously or Intramuscularly in Adult Subjects With Schizophrenia
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 22
- 试验地点
- 2
- 主要终点
- Change in Suicidality via Columbia-Suicide Severity Rating Scale
研究概览
简要总结
To determine the pharmacokinetics, safety and tolerability of brexpiprazole administered subcutaneously or intramuscularly in adults with schizophrenia.
详细描述
This trial is designed to assess the pharmacokinetics, safety and tolerability of brexpiprazole in the treatment of subjects with schizophrenia. The trial will consist of two parts across 13-36 months. The trial population will include approximately 110 male & female subjects between 18 and 64 years of age (inclusive) with a diagnosis of schizophrenia as defined by DSM-V criteria.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Health Services Research
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females between 18 and 64 years of age, inclusive, at the screening visit with a diagnosis of schizophrenia as defined by DSM-V criteria.
- •Body mass index between 18 and 35 kg/m^2 at the screening visit.
- •Good physical health as determined by no clinically significant deviation from normal.
- •Ability to provide informed consent and/or consent obtained from a legally acceptable representative (as required by IRB), prior to the initiation of any protocol-required procedures.
- •Male and female subjects who are surgically sterile, female subjects who have been postmenopausal for at least 12 consecutive months prior to the screening visit, or male subjects/female subjects (of childbearing potential) who agree to remain abstinent or to practice 2 of the approved birth control methods from the screening visit and for at least 150 days after the dose of IMP for a female subject or 180 days after the dose of IMP for a male subject.
排除标准
- •Subjects who have:
- •Met DSM-V criteria for substance use disorder within the past 180 days; including alcohol and benzodiazepines, excluding caffeine/nicotine.
- •A positive drug screen for drugs of abuse (excluding stimulants, other prescribed medications, and marijuana [if in investigator's documented opinion the subject does not meet DSM-V criteria for substance use disorder]).
- •Use of more than 1 psychotropic medication at the screening or baseline visit, except for oral brexpiprazole administered during the brexpiprazole tolerability testing (if applicable) and current oral antipsychotic medication.
- •Use of varenicline beyond screening.
- •Subjects who have participated in any clinical trial involving a psychotropic medication within 1 month prior to the administration of IMP or 5 half-lives from last IMP administration whichever is longer.
- •Subjects who have a significant risk of committing suicide based on history, routine psychiatric status examination, investigator's judgment, or who have an answer of "yes" on questions 4 or 5 on the Baseline Version of the C-SSRS.
- •Subjects currently in an acute relapse of schizophrenia as assessed by the investigator.
- •Subjects with a current DSM-V diagnosis other than schizophrenia. Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.
研究组 & 干预措施
Part A: Single Dose Injection: Subcutaneous
Drug: Brexpiprazole, OPDC-34712 Once, subcutaneous
干预措施: Brexpiprazole, OPDC-34712 (Drug)
Part A: Single Dose Injection: Intramuscular
Drug: Brexpiprazole, OPDC-34712 Once, subcutaneous
干预措施: Brexpiprazole, OPDC-34712 (Drug)
Part B: Cohort 1
Drug: Brexpiprazole, OPDC-34712 Once, SC or IM
干预措施: Brexpiprazole, OPDC-34712 (Drug)
Part B: Cohort 2
Drug: Brexpiprazole, OPDC-34712 Once, SC or IM
干预措施: Brexpiprazole, OPDC-34712 (Drug)
Part B: Cohort 3
Drug: Brexpiprazole, OPDC-34712 Once, SC or IM
干预措施: Brexpiprazole, OPDC-34712 (Drug)
结局指标
主要结局
Change in Suicidality via Columbia-Suicide Severity Rating Scale
时间窗: Part A: Screening to Day 182; Part B: Screening to Day 126
Baseline version and Since Last Visit version of CSSRS will be completed by trained trial center staff
Change in physical exam results
时间窗: Part A: Screening to Day 182; Part B: Screening to Day 126
Investigator or designee will perform complete physical exam and document any clinically significant conditions. Body height and weight will also be measured for BMI calculation and weight will be measured as part of all subsequent physical exams.
Number of reported Adverse Events (AE)
时间窗: Part A: 182 days; Part B: 126 days
Clinical Laboratory Tests
时间窗: Part A: 182 days; Part B: 126 days
Hematology, serum chemistry, urinalysis, drug screen, etc. will be performed.
Change in Systolic/Diastolic blood pressure from screening to end of study
时间窗: Part A: Screening to Day 182; Part B: Screening to Day 126
Heart rate and body temperature will also be obtained prior to PK blood draws and ECG.
ECG Reading
时间窗: Part A: 182 days; Part B: 126 days
12-lead ECG will be collected in triplicate (5 minutes apart). heart rate, ventricular rate, RR interval, PR interval, QRS duration and QT intervals will be recorded. QTcF and corrected QT interval using Bazett's formula will be calculated.
Extrapyramidal Symptoms (EPS) Rating Scale
时间窗: Part A: 182 days; Part B: 126 days
SAS, AIMS \& BARS will be assess by trained trial center staff
Investigator's assessment of injection site
时间窗: Part A: 182 days; Part B: 126 days
Injection site will be assessed. Injection site will also be inspected for seepage after needle is withdrawn.
Visual analog scale (VAS) scores for pain reception
时间窗: Part A: 182 days; Part B: 126 days
次要结局
- Maximum peak plasma concentration (Cmax) [Pharmacokinetics](Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose))
- Time of Cmax (tmax) [Pharmacokinetics](Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose))
- Area under the concentration-time curve (AUC) from time zero to time "t" (Last observable concentration; AUCt) [Pharmacokinetics](Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose))
- AUC from time zero to infinity (AUC∞) [Pharmacokinetics](Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose))
- Terminal-phase elimination half-life (t1/2,z) [Pharmacokinetics](Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose))
- Apparent clearance of drug from plasma after extravascular administration (CL/F; brexpiprazole only) [Pharmacokinetics](Day 1 (predose [within 2 hours prior to dosing] and 4, 8 , and 12 hours postdose))