Double-Blind Randomized Placebo-Control Trial to Evaluate Electrocardiogram Effects of HPN-100 as Defined by Clinical and Supratherapeutic Dose in Healthy Men and Women
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 98
- 试验地点
- 1
- 主要终点
- Safety and tolerability as measured by the rate and severity of adverse events in each treatment group.
研究概览
简要总结
Arm 1:
Primary Objective:
• To determine the safety and tolerability of multiple ascending, supratherapeutic doses of HPN-100.
Arm 2:
Primary Objective:
• To assess the effects of steady-state levels of HPN-100 metabolites (4 phenylbutyric acid [PBA], phenylacetic acid [PAA], and phenylacetylglutamine [PAGN]) on 12-lead electrocardiogram (ECG) parameters in healthy male and female subjects with the primary endpoint being the time-matched change from baseline in the QT interval corrected for heart rate (HR) based on an individual correction method (QTcI).
详细描述
Assess the effects of steady-state levels of HPN-100 metabolites (4-phenylbutryic acid (PBA), phenylacetic acid (PAA), and phenylacetylglutamine (PAGN) on 12-lead electrocardiogram (ECG) parameters in health male and female subjects with the primary endpoint being the time-matched change from baseline in the QT interval corrected for heart rate(HR) based on an individual correction method (QTcl).
Study acquired from Horizon in 2024.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Diagnostic
- 盲法
- Triple (Participant, Care Provider, Investigator)
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
- •Must be in good health
- •Negative hepatitis panel and negative HIV antibody screens
- •Females must be non-pregnant, non-lactating, and either postmenopausal or agree to to use adequate contraceptive methods throughout the study
- •Males must either be sterile or willing to use adequate contraceptive methods throughout the study
- •Willing and able to comply with all trial requirements
- •Able to comprehend and willing to sign an Informed Consent Form (ICF)
排除标准
- •History or clinical manifestations of significant allergic, metabolic, hepatic, renal, endocrine, hematological, pulmonary, cardiovascular, gastrointestinal, urological, neurological, or psychiatric disorders
- •History of hypersensitivity or allergies to any drug compound
- •History of stomach or intestinal surgery or resection
- •History or presence of an abnormal ECG
- •History of alcoholism or drug addiction within 1 year
- •Use of any tobacco-containing or nicotine-containing products within 3 months
- •Participated in any other clinical trial of an investigational drug (or a medical device) within 30 days
- •Use of any prescription medications/products other than contraceptives within 14 days
- •Use of any over-the-counter, non-prescription preparations (including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) within 7 days
- •Test positive for drug(s) of abuse, ethanol, or cotinine
- •Have donated blood or blood components within 30 days
- •Have received blood products within 2 months
- •Have a history of unexplained syncope
- •Have a family history of unexplained sudden death
研究组 & 干预措施
Arm 1
Cohort A: 9 mL HPN-100 or placebo
Cohort B: 12 mL HPN-100 placebo
干预措施: HPN-100 (Drug)
Arm 1
Cohort A: 9 mL HPN-100 or placebo
Cohort B: 12 mL HPN-100 placebo
干预措施: HPN-100 or Placebo (Drug)
Arm 2
This study requires 4 periods. In each of the periods you will receive one of the dose groups listed below. At the completion of the study you will have participated in all 4 dose groups. The order in which you participate in each dose group will be randomly assigned.
Dose Group A: 9 mL placebo via oral syringe 3 times daily for 3 days
Dose Group B: single oral dose of 400 mg moxifloxacin on study Day 3
Dose Group C: 6 mL HPN-100 and 3 mL placebo via oral syringe 3 times daily for 3 days
Dose Group D: 9 mL HPN-100 via oral syringe 3 times daily for 3 days
干预措施: Placebo (Drug)
Arm 2
This study requires 4 periods. In each of the periods you will receive one of the dose groups listed below. At the completion of the study you will have participated in all 4 dose groups. The order in which you participate in each dose group will be randomly assigned.
Dose Group A: 9 mL placebo via oral syringe 3 times daily for 3 days
Dose Group B: single oral dose of 400 mg moxifloxacin on study Day 3
Dose Group C: 6 mL HPN-100 and 3 mL placebo via oral syringe 3 times daily for 3 days
Dose Group D: 9 mL HPN-100 via oral syringe 3 times daily for 3 days
干预措施: Moxifloxacin (Drug)
Arm 2
This study requires 4 periods. In each of the periods you will receive one of the dose groups listed below. At the completion of the study you will have participated in all 4 dose groups. The order in which you participate in each dose group will be randomly assigned.
Dose Group A: 9 mL placebo via oral syringe 3 times daily for 3 days
Dose Group B: single oral dose of 400 mg moxifloxacin on study Day 3
Dose Group C: 6 mL HPN-100 and 3 mL placebo via oral syringe 3 times daily for 3 days
Dose Group D: 9 mL HPN-100 via oral syringe 3 times daily for 3 days
干预措施: HPN-100 (Drug)
结局指标
主要结局
Safety and tolerability as measured by the rate and severity of adverse events in each treatment group.
时间窗: 3-day treatment period
Changes from baseline QTcI as a measure of effects of study-state HPN-100 metabolites: PBA, PAA, and PAGN
时间窗: 4 treatment regimens for 3 days with a 4 day minimum washout period between treatments
次要结局
- Correlate time-matched QTcI change from baseline and serum levels of PBA, PAA, and PAGN drawn on Day 1, Day 2, Day 3, and Day 4(4 treatment regimens for 3 days with a 4 day minimum washout period between treatments)
- Correlate time-matched ECG waveform changes to steady-state levels of HPN-100 by using QTcB and QTcF formulas to assess ECG morphologic changes.(4 treatment regimens for 3 days with a 4 day minimum washout period between treatments)
- Gender differences in metabolism of HPN-100 as measured by time-matched serum levels of HTN-100, PBA, PAA, and PAGN via samples drawn on Day 1, Day 2, Day 3, and Day 4.(4 treatment regimens for 3 days with a 4 day minimum washout period between treatments)
- Number and severity of adverse events in each treatment group.(4 treatment regimens for 3 days with a 4 day minimum washout period between treatments)