A Randomized, Placebo- and Positive-controlled, Crossover Study to Assess the Effect of Olpasiran (AMG 890) on QT/QTc Intervals in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 32
- 试验地点
- 1
- 主要终点
- Placebo-corrected Change From Baseline in QT Corrected for Heart Rate (HR) Interval Based on the Fridericia Correction (QTcF) (ΔΔQTcF) After Olpasiran Dosing
研究概览
简要总结
The primary objective of the study is:
• To assess the effects of a single therapeutic and supratherapeutic dose of olpasiran on the placebo-corrected change from baseline in QT corrected for heart rate (ΔΔQT)/QTc interval in healthy participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Provide informed consent prior to starting study activities.
- •Healthy male or female participants, between 18 and 60 years of age (inclusive) at the time of Screening. Females must be of nonchildbearing potential.
- •Body mass index between 18 and 30 kg/m^2 (inclusive) at the time of Screening. Participants must have a body mass ≥ 50kg.
排除标准
- •History or evidence, at Screening or Check-in, of clinically significant disorder, condition, or disease not otherwise excluded that, in the opinion of the Investigator (or designee), would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion.
- •History or current signs or symptoms of cardiovascular disease, including but not limited to myocardial infarction, congenital heart disease, valvular heart disease coronary revascularization, or angina.
- •History or evidence of clinically significant arrhythmia at screening, including any clinically significant findings on the ECG taken at Check-in.
- •Systolic blood pressure > 150 mmHg or < 90 mmHg, or diastolic blood pressure > 90 mmHg or < 50 mmHg, or HR ≤ 40 and > 100 bpm, at Screening or Check-in; one repeat blood pressure measurement will be allowed at Screening and Check-in.
- •History suggestive of esophageal (including esophageal spasm, esophagitis), gastric, or duodenal ulceration or bowel disease (including but not limited to peptic ulceration, gastrointestinal bleeding, ulcerative colitis, Crohn's disease, or irritable bowel syndrome), or a history of gastrointestinal surgery other than uncomplicated appendectomy and hernia repair.
- •Inability to swallow oral medication or history of malabsorption syndrome.
- •History of hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee) and in consultation with the Sponsor.
- •History of major bleeding disorder (for example: hemophilia, von Willebrand disease, clotting factor deficiencies, etc).
- •Participant has received a dose of an investigational drug within the past 90 days or have previously completed or withdrawn from this study or any other study investigating olpasiran or have previously received olpasiran.
研究组 & 干预措施
Treatment A
All participants will be randomized to 1 of 12 treatment sequences and receive a single dose of one of the following treatments, according to the randomization schedule:
Treatment A: placebo Treatment B: dose level 1 olpasiran Treatment C: dose level 2 olpasiran Treatment D: moxifloxacin
干预措施: Placebo (Other)
Treatment B
All participants will be randomized to 1 of 12 treatment sequences and receive a single dose of one of the following treatments, according to the randomization schedule:
Treatment A: placebo Treatment B: dose level 1 olpasiran Treatment C: dose level 2 olpasiran Treatment D: moxifloxacin
干预措施: Olpasiran (Drug)
Treatment C
All participants will be randomized to 1 of 12 treatment sequences and receive a single dose of one of the following treatments, according to the randomization schedule:
Treatment A: placebo Treatment B: dose level 1 olpasiran Treatment C: dose level 2 olpasiran Treatment D: moxifloxacin
干预措施: Olpasiran (Drug)
Treatment D
All participants will be randomized to 1 of 12 treatment sequences and receive a single dose of one of the following treatments, according to the randomization schedule:
Treatment A: placebo Treatment B: dose level 1 olpasiran Treatment C: dose level 2 olpasiran Treatment D: moxifloxacin
干预措施: Moxifloxacin (Drug)
结局指标
主要结局
Placebo-corrected Change From Baseline in QT Corrected for Heart Rate (HR) Interval Based on the Fridericia Correction (QTcF) (ΔΔQTcF) After Olpasiran Dosing
时间窗: Day 3 of Treatment Period 4 (up to approximately 9.5 weeks)
次要结局
- Placebo-corrected Change From Baseline in PR Interval(Up to 10 weeks)
- Half-life of Olpasiran (t1/2)(Up to 10 weeks)
- Area Under the Curve From Time 0 to the Last Quantifiable Concentration (AUClast)(Up to 10 weeks)
- Change From Baseline in QTcF(Up to 10 weeks)
- Area Under the Curve From Time 0 to Infinity (AUCinf)(Up to 10 weeks)
- Change From Baseline in HR(Up to 10 weeks)
- ΔΔQTcF After Moxifloxacin Dosing(Up to 10 weeks)
- Number of Participants With Treatment-emergent Serious Adverse Events(Up to 10 weeks)
- Time to Cmax (tmax) of Olpasiran(Up to 10 weeks)
- Change From Baseline in PR Interval(Up to 10 weeks)
- Maximum Observed Concentration (Cmax) of Olpasiran(Up to 10 weeks)
- Placebo-corrected Change From Baseline in QRS Interval(Up to 10 weeks)
- Number of Participants with Categorical Outliers Related to the Following ECG parameter: QTcF, HR, PR, and QRS(Up to 10 weeks)
- Frequency of Treatment-emergent Changes in Electrocardiogram (ECG) Morphology(Up to 10 weeks)
- Number of Participants With Treatment-emergent Adverse Events(Up to 10 weeks)
- Change From Baseline in QRS Interval(Up to 10 weeks)
- Placebo-corrected Change From Baseline in HR(Up to 10 weeks)