A Parallel-arm, Double-blind, Placebo and Positive Controlled Multiple Oral Dose Administration Trial to Evaluate the Effects of OPC-34712 on QT/QTc in Subjects With Schizophrenia or Schizoaffective Disorder
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 218
- 试验地点
- 1
- 主要终点
- Time-matched QTcI Change From Baseline (Day -1) Corrected for Placebo on Day 11 Following Brexpiprazole Treatment.
研究概览
简要总结
The purpose of this study is to establish pharmacodynamics (PD), pharmacokinetics (PK), and adverse event (AE) profile of OPC-34712 administered to schizophrenic/schizoaffective subjects. The goals of this trial are three-fold:
- To determine the effect of OPC-34712 on the individual QT interval (QTcI) corrected for placebo
- To determine the effect of moxifloxacin on QTcI
- To examine the concentration-effect relationship of OPC-34712 and moxifloxacin on QTcI
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
- Triple (Participant, Care Provider, 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 subjects between 18 and 55 years of age, inclusive, with a diagnosis of schizophrenia or schizoaffective disorder as defined by DSM-IV-TR criteria.
- •Body mass index of 19 to 35 kg/m2.
排除标准
- •Females who are pregnant or lactating. A negative serum pregnancy test must be confirmed prior to the first dose of trial medication for all female subjects.
- •Subjects presenting with a first episode of schizophrenia or schizoaffective disorder based on the clinical judgment of the investigator.
- •Subjects who have received continuous medication therapy to treat schizophrenia or schizoaffective disorder for less than 6 months prior to washout.
- •Subjects with schizophrenia or schizoaffective disorder that are considered resistant/refractory to antipsychotic treatment by history, who have a history of failure to clozapine, or who are responsive only to clozapine treatment.
- •Subjects with a current DSM-IV-TR Axis I diagnosis other than schizophrenia or schizoaffective disorder.
- •Hospitalization for an exacerbation of schizophrenia or schizoaffective disorder within 3 months prior to randomization.
- •Subjects who have a history of or who have evidence of other medical and/or neurological conditions that would expose them to an undue risk of a significant AE or interfere with assessments of safety or efficacy during the course of the trial.
- •Subjects with a history of neuroleptic malignant syndrome.
- •Subjects with a history of seizure disorder.
- •Subjects who meet DSM-IV-TR criteria for substance dependence within 6 months prior to randomization.
研究组 & 干预措施
Arm 3 (moxifloxacin, placebo)
Arm 3 will be administered 400 mg moxifloxacin (positive control) plus OPC-34712 placebo for 1 day and OPC-34712 placebo QD for 11 days.
干预措施: Moxifloxacin (Drug)
Arm 1 (OPC-34712, placebo)
Arm 1 will be administered 4 mg OPC-34712 once daily (QD) for 11 days and OPC-34712 placebo for 1 day.
干预措施: OPC-34712 (4mg) (Drug)
Arm 1 (OPC-34712, placebo)
Arm 1 will be administered 4 mg OPC-34712 once daily (QD) for 11 days and OPC-34712 placebo for 1 day.
干预措施: Placebo (Drug)
Arm 2 (OPC-34712, placebo)
Arm 2 will be administered 12 mg OPC-34712 QD for 11 days and OPC-34712 placebo for 1 day.
干预措施: OPC-34712 (12mg) (Drug)
Arm 2 (OPC-34712, placebo)
Arm 2 will be administered 12 mg OPC-34712 QD for 11 days and OPC-34712 placebo for 1 day.
干预措施: Placebo (Drug)
Arm 3 (moxifloxacin, placebo)
Arm 3 will be administered 400 mg moxifloxacin (positive control) plus OPC-34712 placebo for 1 day and OPC-34712 placebo QD for 11 days.
干预措施: Placebo (Drug)
Arm 4 (moxifloxacin, placebo)
Arm 4 will be administered OPC-34712 placebo QD for 11 days and 400 mg moxifloxacin (positive control) plus OPC-34712 placebo for one day.
干预措施: Moxifloxacin (Drug)
Arm 4 (moxifloxacin, placebo)
Arm 4 will be administered OPC-34712 placebo QD for 11 days and 400 mg moxifloxacin (positive control) plus OPC-34712 placebo for one day.
干预措施: Placebo (Drug)
结局指标
主要结局
Time-matched QTcI Change From Baseline (Day -1) Corrected for Placebo on Day 11 Following Brexpiprazole Treatment.
时间窗: Day 11 (Hours 1, 2, 3, 4, 5, 6, 8, 12, 16, 24)
Pharmacodynamics endpoint is the time-matched corrected QT interval (QTcI) change from baseline (Day -1) corrected for placebo on Day 11 following brexpiprazole treatment. The primary QT to QTc correction formula (QTcI) was determined for each participant using the participant's baseline (Day -1 placebo) ECG data. The QT correction formula QT / (RR)k was derived using log-log-linear regression, where log (QT) = a + k × log (RR) + ε to estimate the exponent (k).
Number of Participants With Adverse Events (AE) and Clinically Important Changes in Vital Signs, Physical Examinations, Laboratory Tests, and Standard ECGs (Electrocardiogram).
时间窗: AEs were recorded from Screening (informed consent was signed) during the 12-day treatment period to follow-up 30 (+ 2) days post-last dose of study medication
Clinically important changes in vital signs, physical examinations, laboratory tests and ECGs were by and large reflected in AE/SAE (which are presented in safety section) of this report.
Maximum Peak Plasma Concentration (Cmax) of Brexpiprazole and Moxifloxacin.
时间窗: Day 11
Pharmacokinetics endpoint is the maximum (peak) plasma concentration (Cmax) of brexpiprazole and moxifloxacin. Values for Cmax were determined directly from the observed data. Blood samples were collected on Days -1, 1, 11, and 12 at predose, and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose or at ET.
Time to Maximum (Peak) Plasma Concentration (Tmax) of Brexpiprazole and Moxifloxacin.
时间窗: Day 11
Pharmacokinetics endpoint is the time to maximum (peak) plasma concentration (tmax) of brexpiprazole and moxifloxacin. Values for tmax were determined directly from the observed data. Blood samples were collected on Days -1, 1, 11, and 12 at predose, and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose or at ET.
Area Under the Plasma Concentration-time Curve During Dosing (AUCT).
时间窗: Day 11
Pharmacokinetics endpoint is the area under the concentration-time curve from time zero to 24 hours (AUC0-24h) of brexpiprazole and moxifloxacin. Area under the plasma concentration-time curve during the dosing interval at steady-state (AUCT) value was estimated using the linear trapezoidal rule; the value reported represent the area under the curves to the last time point during that day. Blood samples were collected on Days -1, 1, 11, and 12 at predose, and 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose or at ET.
次要结局
- Number of Participants Noted With Time-matched Change in Mean QTcI Change From Baseline for Assay Sensitivity of Moxifloxacin Treatment Corrected for Placebo at Day 11.(Baseline, Day 11)
- Change From Baseline in Summary of Maximum QTcI on Day 11 Minus Mean QTcI on Day -1 (Baseline).(Baseline, Day 11)
- Change From Baseline in Summary of Maximum QTcI on Day 11 Minus Maximum QTcI on Day -1 (Baseline).(Baseline, Day 11)
- Number of Participants With QTcI Interval Between 30 and 60 Msec on Day 11.(Day 11)
- Number of Participants With QTcI Interval > 60 Msec on Day 11.(Day 11)
- Number Participants Noted With New Incidence of QT Interval of > 500 Msec on Day 11.(Day 11)
- Number of Participants With New Incidence of ECG Morphology Abnormalities on Day 11.(Day 11)
- Number of Participants With Maximum Change From Baseline to the On-treatment ECG Values on Day 11 for Heart Rate (HR), PR Interval, and QRS Interval.(Day 11)