A Phase 1, Randomized, Double-blind, Placebo-controlled, Single-ascending Dose Study With a Food-Effect Cohort to Evaluate the Safety, Tolerability, and Pharmacokinetics of AMG 581 in Healthy Subjects and Subjects With Schizophrenia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Changes in heart rate
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, safety and tolerability of AMG 581 in healthy participants and subjects with schizophrenia.
详细描述
The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetic profile of single-ascending oral doses of AMG 581 in healthy subjects and subjects diagnosed with schizophrenia or schizoaffective disorder receiving antipsychotic treatment.
This will be a placebo-controlled, single-ascending oral-dose study of AMG 581 with a food-effect cohort. Approximately 70 subjects will be enrolled. This study will enroll healthy subjects into 8 cohorts (Cohorts 1,2,3,4,5,6,8 and 9), and subjects with schizophrenia or schizoaffective disorder receiving antipsychotic medication into a single cohort (Cohort 7).
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
- •Provide informed consent prior to initiation of any study-related procedure
- •Male and female subjects ≥ 18 to ≤ 45 years of age at the time of screening
- •Non-nicotine or non-tobacco for healthy subjects
- •No history of relevant medical disorders
- •BMI ≥ 18.0 and ≤ 30.0
- •Non-reproductive females
- •Males practicing effect birth control
- •Avoid tanning/direct sunlight
- •Willing to consume high-fat meal
- •Schizophrenia or schizoaffective disorder
- •PANSS score ≤ 4 points on a few 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
- •Tremor or gait disturbance
- •History of hereditary shorten QT syndrome
- •Malignancy or tumor (other than skin cancers)
- •History of GI disease
- •QTc ≥ 450 msec or ≤ 380 msec
- •Creatinine clearance < 80 mL/min at screening
研究组 & 干预措施
Placebo
干预措施: Placebo (Drug)
AMG 581
干预措施: AMG 581 (Drug)
结局指标
主要结局
Changes in heart rate
时间窗: 15 days
Summaries over time and/or changes from baseline over time in heart rate
Changes in respiratory rate
时间窗: 15 days
Summaries over time and/or changes from baseline over time in respiratory rate
Scores at each study visit for Simpson Angus Scale (SAS)
时间窗: 15 days
Summaries over time and/or changes from baseline over time in Simpson Angus Scale (SAS) score
Reported treatment-emergent adverse events
时间窗: 15 days
Number and percent of subjects experiencing adverse events
Scores at each study visit and summary by cohort for Barnes Akathisia Rating Scale (BARS)
时间窗: 15 days
Summaries over time and/or changes from baseline over time in Barnes Akathisia Rating Scale (BARS) score
Subject incidence of treatment-emergent suicidal ideation and behavior as measured by Columbia-Suicide Severity Rating Scale (C-SSRS)
时间窗: 15 days
Subject incidence of treatment-emergent suicidal ideation and behavior as measured by Columbia-Suicide Severity Rating Scale (C-SSRS) summarized by cohort
Changes in temperature
时间窗: 15 days
Summaries over time and/or changes from baseline over time in temperature
Changes in ECGs
时间窗: 15 days
Summaries over time and/or changes from baseline over time in ECGs
Changes in systolic/diastolic blood pressure
时间窗: 15 days
Summaries over time and/or changes from baseline over time in systolic and/or diastolic blood pressure
次要结局
- Peak plasma concentration (Cmax)(15 days)
- Area under the plasma concentration versus time curve (AUC)(15 days)
- Median of tmax(15 days)