A Phase I, Randomized, Placebo-controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of AMG 581 in Healthy Subjects or Subjects With Schizophrenia or Schizoaffective Disorder on Antipsychotic Medication
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 52
- 试验地点
- 2
- 主要终点
- Reported treatment-emergent adverse events
研究概览
简要总结
The purpose of this study is to find out the time it takes to absorb, distribute, breakdown and remove the drug from the body in healthy participants and subjects with schizophrenia and whether it causes any side effects.
详细描述
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetic profile of ascending multiple oral doses of AMG 581 in healthy subjects or subjects with schizophrenia or schizoaffective disorder on antipsychotic medication. The study will also assess the effects of AMG 581 on midazolam PK in healthy subjects or subjects with schizophrenia or schizoaffective disorder on antipsychotic medication.
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 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Provided informed consent prior to initiation of any study-specific activities/procedures; -male or female subjects should be between the ages of 18 and 45 years (18-55 years for subjects with schizophrenia);-non-nicotine or non-tobacco (healthy subjects only); - no history of relevant medical disorders; - BMI ≥ 18.0; - females of non-reproductive potential; - males practicing effective birth control; - avoid tanning/direct sunlight; - schizophrenia or schizoaffective disorder; PANSS score ≤ 4 points on following items (i.e. conceptual disorganization, hallucinatory behavior, excitement, suspiciousness/persecution, hostility, depression, anxiety, disorientation, uncooperativeness, disturbance of volition, and poor impulse control) / total score ≤ 80 points
排除标准
- •females lactating/breastfeeding; pregnant partners of male subjects; essential tremor or gait disturbance; - history of hereditary shorten QT syndrome; - malignancy or tumor (other than skin cancers); - history of GI disease that could interfere with absorption; - QTc ≥ 450 msec or ≤ 380 msec; - HbA1c ≥ 7%;
研究组 & 干预措施
AMG 581 - Dose 1
干预措施: AMG 581 (Drug)
AMG 581 - Dose 2
干预措施: AMG 581 (Drug)
AMG 581 - Dose 3
干预措施: AMG 581 (Drug)
AMG 581 - Dose 4
干预措施: AMG 581 (Drug)
Placebo - Dose 1
干预措施: AMG 581 (Drug)
Placebo - Dose 1
干预措施: Placebo (Drug)
Placebo - Dose 2
干预措施: Placebo (Drug)
Placebo - Dose 3
干预措施: Placebo (Drug)
Placebo - Dose 4
干预措施: Placebo (Drug)
AMG 581/Midazolam - Drug Interaction
干预措施: AMG 581 (Drug)
AMG 581/Midazolam - Drug Interaction
干预措施: Midazolam (Drug)
结局指标
主要结局
Reported treatment-emergent adverse events
时间窗: 39 days
Number and percent of subjects experiencing adverse events
Changes in systolic/diastolic blood pressure
时间窗: 39 days
Summaries over time and/or changes from baseline over time in systolic and/or diastolic blood pressure
Changes in heart rate
时间窗: 39 days
Summaries over time and/or changes from baseline over time in heart rate
Maximum post-baseline QTc values and number and percentage of subjects with maximum post-baseline QTc values exceeding prespecified limits in each group
时间窗: 39 days
Subjects' maximum post-baseline values and the number and percentage of subjects in each group
Scores at each study visit for Simpson Angus Scale (SAS)
时间窗: 39 days
Summaries over time and/or changes from baseline over time in changes in Simpson Angus Scale (SAS) score
Scores at each study visit for Barnes Akathisia Rating Scale (BARS)
时间窗: 39 days
Summaries over time and/or changes from baseline over time in in Barnes Akathisia Rating Scale (BARS) score
Changes in respiratory rate
时间窗: 39 days
Summaries over time and/or changes from baseline over time in respiratory rate
Changes in temperature
时间窗: 39 days
Summaries over time and/or changes from baseline over time in temperature
Changes in ECGs
时间窗: 39 days
Summaries over time and/or changes from baseline over time in ECGs
Maximum change from baseline in QTc in ECGs and number and percentage of subjects with maximum changes exceeding prespecified limits in each group
时间窗: 39 days
Subjects' maximum change from baseline in QTc and the number and percentage of subjects in each group
Subject incidence of treatment-emergent suicidal ideation and behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
时间窗: 39 days
Subject incidence of treatment-emergent suicidal ideation and behavior as assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS) summarized by cohort
次要结局
- Compare PK parameter (Cmax) between Day 1 and Day 18(18 days)
- Compare PK parameter (AUC) between Day 1 and Day 18(18 days)
- Compare PK parameter (tmax) Compare PK parameter (tmax) between Day 1 and Day 18(18 days)
- Plasma PK parameters of midazolam and 1-OH midazolam(36 days)