Trial to Evaluate the Effects of OPC-34712 on QT/QTc in Subjects With Schizophrenia or Schizoaffective Disorder
2015年9月29日 更新者：Otsuka Pharmaceutical Development & Commercialization, Inc.
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
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
研究概览
研究类型
介入性
注册 (实际的)
218
阶段
- 阶段1
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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California
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Long Beach、California、美国、90806
- Otsuka Investigational Site
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San Diego、California、美国、92102
- Otsuka Investigational Site
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Florida
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Fort Lauderdale、Florida、美国、33308
- Otsuka Investigational Site
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Kansas
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Overland Park、Kansas、美国、66212
- Otsuka Investigational Site
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Maryland
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Rockville、Maryland、美国、20850
- Otsuka Investigational Site
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Missouri
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St. Louis、Missouri、美国、63118
- Otsuka Investigational Site
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Pennsylvania
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Philadelphia、Pennsylvania、美国、19139
- Otsuka Investigational Site
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Texas
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Austin、Texas、美国、78754
- Otsuka Investigational Site
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 55年 (成人)
接受健康志愿者
不
有资格学习的性别
全部
描述
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：三倍
武器和干预
参与者组/臂 |
干预/治疗 |
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有源比较器：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.
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Arms assigned to this intervention receive 4mg.
OPC-34712 placebo
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有源比较器：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.
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OPC-34712 placebo
Arms assigned to this intervention receive 12mg.
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有源比较器：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.
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OPC-34712 placebo
Arms assigned to this intervention will receive 400mg.
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有源比较器：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.
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OPC-34712 placebo
Arms assigned to this intervention will receive 400mg.
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Time-matched QTcI Change From Baseline (Day -1) Corrected for Placebo on Day 11 Following Brexpiprazole Treatment.
大体时间：Day 11 (Hours 1, 2, 3, 4, 5, 6, 8, 12, 16, 24)
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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).
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Day 11 (Hours 1, 2, 3, 4, 5, 6, 8, 12, 16, 24)
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Number of Participants With Adverse Events (AE) and Clinically Important Changes in Vital Signs, Physical Examinations, Laboratory Tests, and Standard ECGs (Electrocardiogram).
大体时间：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
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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.
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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
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Maximum Peak Plasma Concentration (Cmax) of Brexpiprazole and Moxifloxacin.
大体时间：Day 11
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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.
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Day 11
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Time to Maximum (Peak) Plasma Concentration (Tmax) of Brexpiprazole and Moxifloxacin.
大体时间：Day 11
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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.
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Day 11
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Area Under the Plasma Concentration-time Curve During Dosing (AUCT).
大体时间：Day 11
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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.
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Day 11
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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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.
大体时间：Baseline, Day 11
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New onset (> 450, > 480, or > 500 msec) in QTc was defined as a participant who attained a QTc > 450, > 480, > 500 msec during Day 11 but not on Day -1.
The number of participants were noted with time-matched change in mean QTcI change from Baseline for assay sensitivity of moxifloxacin treatment corrected for placebo.
The primary QT to QTc correction formula (QTcI) were determined for each participant using the participant's Baseline (Day -1 placebo) ECG data.
The QT correction formula QT / (RR)k were derived using log-log-linear regression, where log (QT) = a + k × log (RR) + ε to estimate the exponent (k).
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Baseline, Day 11
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Change From Baseline in Summary of Maximum QTcI on Day 11 Minus Mean QTcI on Day -1 (Baseline).
大体时间：Baseline, Day 11
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The primary QT to QTc correction formula (QTcI) were determined for each participant using the participant's Baseline (Day -1 placebo) ECG data.
The QT correction formula QT / (RR)k were derived using log-log-linear regression, where log (QT) = a + k × log (RR) + ε to estimate the exponent (k).
The change form Baseline in summary of maximun QTcI on Day 11 minus mean QTcI on Day -1 (Baseline) is presented here.
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Baseline, Day 11
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Change From Baseline in Summary of Maximum QTcI on Day 11 Minus Maximum QTcI on Day -1 (Baseline).
大体时间：Baseline, Day 11
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The primary QT to QTc correction formula (QTcI) were determined for each participant using the participant's Baseline (Day -1 placebo) ECG data.
The QT correction formula QT / (RR)k were derived using log-log-linear regression, where log (QT) = a + k × log (RR) + ε to estimate the exponent (k).
The change from Baseline in summary of maximum QTcI on Day 11 minus maximum QTcI on Day -1 (Baseline) is presented here.
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Baseline, Day 11
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Number of Participants With QTcI Interval Between 30 and 60 Msec on Day 11.
大体时间：Day 11
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The primary QT to QTc correction formula (QTcI) were determined for each participant using the participant's Baseline (Day -1 placebo) ECG data.
The QT correction formula QT / (RR)k were derived using log-log-linear regression, where log (QT) = a + k × log (RR) + ε to estimate the exponent (k).
Participants with QTcI interval change between 30 to 60 msec were presented here.
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Day 11
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Number of Participants With QTcI Interval > 60 Msec on Day 11.
大体时间：Day 11
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The primary QT to QTc correction formula (QTcI) were determined for each participant using the participant's Baseline (Day -1 placebo) ECG data.
The QT correction formula QT / (RR)k were derived using log-log-linear regression, where log (QT) = a + k × log (RR) + ε to estimate the exponent (k).
Participants with QTcI interval change of > 60 msec on Day 11 were presented here.
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Day 11
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Number Participants Noted With New Incidence of QT Interval of > 500 Msec on Day 11.
大体时间：Day 11
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The number of participants who were noted with new incidence of QT interval of > 500 msec on Day 11 and a 12-lead ECG was used.
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Day 11
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Number of Participants With New Incidence of ECG Morphology Abnormalities on Day 11.
大体时间：Day 11
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Participants with incidence of ECG morphology abnormalities on Day 11 (participants who had abnormalities during Day 11 but not at Day -1) were noted.
Types of abnormalities included appearance of abnormal U waves, negative T waves, elevation of ST segment, depression of ST segment, second degree heart block, third degree heart block, right bundle branch block, and left bundle branch block.
ECGs were sampled at predose and approximately 1, 2, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours postdose on Days -1, 1, 11, and 12.
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Day 11
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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.
大体时间：Day 11
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Changes in HR with values 25% decrease from Day -1 and HR < 50 bpm and 25% increase from Day -1 and HR > 100 bpm; PR interval of greater than or equal to 25% change from Day -1 and PR > 200 msec; QRS interval of Greater than or equal to 25% change from Day -1 and > 100 msec were noted on Day 11.
Maximum change from baseline to the on-treatment ECG values on Day 11 for heart rate.
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Day 11
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2011年7月1日
初级完成 (实际的)
2012年2月1日
研究完成 (实际的)
2012年3月1日
研究注册日期
首次提交
2011年8月8日
首先提交符合 QC 标准的
2011年8月25日
首次发布 (估计)
2011年8月26日
研究记录更新
最后更新发布 (估计)
2015年10月29日
上次提交的符合 QC 标准的更新
2015年9月29日
最后验证
2015年9月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.