A Phase 1, Placebo-controlled, Within-Cohort Randomized, Double-blind, Single and Multiple Ascending Dose Study of the Safety, Tolerability and Pharmacokinetics of 7HP349 in Normal Healthy Male Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Safety and tolerability of 7HP349 in healthy male subjects as assessed by incidence of treatment-emergent adverse events according to CTCAE v5.0 criteria
研究概览
简要总结
This study will evaluate the safety, tolerability and pharmacokinetics of 7HP349, an allosteric integrin activator, in healthy male subjects
详细描述
This first-in-human (FIH) study consists of a placebo-controlled, sequential, dose escalation study to determine the safety, tolerability and pharmacokinetics (PK) of 7HP349 following single and multiple oral dose administration to healthy male subjects, with a separate, open-label food effect cohort at the optimal pharmacokinetic dose (OPD). The study will be carried out in 3 parts.
Part A: This is a placebo-controlled, within-cohort randomized, double-blind, sequential, single ascending dose (SAD) escalation study to determine the safety, tolerability and PK of 7HP349 following administration of single oral doses in healthy male subjects, and to define the OPD of 7HP349.
Part B: This is a placebo-controlled, within-cohort randomized, double-blind, sequential, multiple ascending dose (MAD) escalation study to determine the safety, tolerability and PK of 7HP349 following up to 5 once daily oral doses in healthy male subjects.
Part C: This is a randomized, open label, two-treatment, three-period, crossover study to evaluate the effect of the fed or fasting prandial state on the single dose PK of 7HP349.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 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
- Male
- 接受健康志愿者
- 是
入选标准
- •Healthy males between the ages of 18 and 45 years, inclusive
- •Normal clinical chemistry, hepatic function, hematology, thyroid function
- •Body mass index (BMI) of 19 to 30 kg/m2 inclusive and body weight not less than 60 kg
- •Agree to refrain from consuming products containing grapefruit, pomelo, star fruit or Seville oranges for at least 7 days before the first dose of study drug until the final discharge evaluation
- •Positive immune status as defined in serum as measles, mumps, varicella-zoster viruses (VZR); Antibody Index (AI) ≥ 1.1, and positive Rubella: AI ≥ 1.0
排除标准
- •Clinically significant history of disorders, infections or drug hypersensitivity as determined by the Investigator
- •History of malignancy, with the exception of cured basal cell or squamous cell carcinoma of the skin
- •Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody
- •Current treatment or treatment within 30 days with another investigational medication
研究组 & 干预措施
Placebo Capsules
Part A: Placebo Capsules (5 cohorts); Part B: Placebo Capsules (2 cohorts)
干预措施: Placebo Single Ascending Dose (Drug)
7HP349 Capsules
Part A: 7HP349 Capsules (5 cohorts); Part B: 7HP349 Capsules (2 cohorts); Part C: 7HP349 Capsules (3-period cross-over)
干预措施: 7HP349 Single Ascending Dose (Drug)
7HP349 Capsules
Part A: 7HP349 Capsules (5 cohorts); Part B: 7HP349 Capsules (2 cohorts); Part C: 7HP349 Capsules (3-period cross-over)
干预措施: 7HP349 Multiple Ascending Dose (Drug)
7HP349 Capsules
Part A: 7HP349 Capsules (5 cohorts); Part B: 7HP349 Capsules (2 cohorts); Part C: 7HP349 Capsules (3-period cross-over)
干预措施: 7HP349 Food Effect (Drug)
Placebo Capsules
Part A: Placebo Capsules (5 cohorts); Part B: Placebo Capsules (2 cohorts)
干预措施: Placebo Multiple Ascending Dose (Drug)
结局指标
主要结局
Safety and tolerability of 7HP349 in healthy male subjects as assessed by incidence of treatment-emergent adverse events according to CTCAE v5.0 criteria
时间窗: 17 days
Safety assessments will include evaluation of incidence of treatment-emergent adverse events (AEs) according to CTCAE v5.0 criteria, including vital signs, resting electrocardiogram (ECG) parameters, standard hematology, chemistry, urinalysis and other tests
次要结局
- Pharmacokinetics of 7HP349 in healthy male subjects as assessed by maximum plasma concentration (Cmax) towards determination of the optimal pharmacokinetic dose (OPD)(17 days)
- Pharmacokinetics of 7HP349 in healthy male subjects as assessed by plasma exposure (AUClast and/or AUCinf) towards determination of the optimal pharmacokinetic dose (OPD)(17 days)
- Pharmacokinetics of 7HP349 in healthy male subjects as assessed by exposure in urine towards determination of the optimal pharmacokinetic dose (OPD)(17 days)
- Pharmacokinetics of 7HP349 in healthy male subjects as assessed by renal clearance (CLr) towards determination of the optimal pharmacokinetic dose (OPD)(17 days)
- Effect of food on the pharmacokinetics of 7HP349 in healthy male subjects as assessed by measurement of maximum plasma concentration (Cmax) in fed individuals(28 days)
- Effect of food on the pharmacokinetics of 7HP349 in healthy male subjects as assessed by measurement of maximum plasma exposure (AUClast and/or AUCinf) in fed individuals(28 days)
- Effect of food on the pharmacokinetics of 7HP349 in healthy male subjects as assessed by measurement of maximum plasma concentration (Cmax) in fasted individuals(28 days)
- Effect of food on the pharmacokinetics of 7HP349 in healthy male subjects as assessed by measurement of maximum plasma exposure (AUClast and/or AUCinf) in fasted individuals(28 days)
- Effect of food on the pharmacokinetics of 7HP349 in healthy male subjects as assessed by measurement of the Geometric Mean Ratio (GMR) of the maximum plasma concentration (Cmax) in fed vs. fasted individuals(28 days)
- Effect of food on the pharmacokinetics of 7HP349 in healthy male subjects as assessed by measurement of the Geometric Mean Ratio (GMR) of the plasma exposure (AUClast and/or AUCinf) in fed vs. fasted individuals(28 days)