A First-in-human, Randomized, Sponsor Open-label, Participant and Investigator Blinded, Placebo-controlled, Single Ascending Dose Study to Explore the Safety, Tolerability and Pharmacokinetics of XXB750 in Healthy Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 77
- 试验地点
- 1
- 主要终点
- Number of participants with Adverse Events
研究概览
简要总结
This study was a randomized, participant and investigator-blinded, placebo-controlled, single-ascending dose study, consisting of 9 sequential dose cohorts (1 mg, 3 mg, 10 mg, 30 mg, 60 mg, 120 mg, 240 mg, 450 mg and 600 mg) and a Japanese ethnic sensitivity cohort (240 mg dose)
详细描述
Eligible healthy participants with normal blood pressure (SBP: 110-139 mmHg; DBP: 70-89 mmHg) were randomized into dose cohorts 1 - 240 mg. Eligible healthy participants with elevated blood pressure (SBP: 139 - 159 mmHg; DBP: 75 - 95 mmHg) were randomized into dose cohorts 450 and 600 mg. Each participant received a subcutaneous single dose of either XXB750 or placebo. In total, the duration of the study was 151 days, including the full Screening period of up to 28 days, safety, pharmacokinetics and pharmacodynamics assessments over a period of 91 days, and a 30-day safety follow up call after the end of study visit.
Sentinel dosing will be applied in this FIH study at each new dose level to ensure participant's safety and minimize the number of participants that may experience symptomatic hypotension, especially for sustained periods of time attributing to the long acting nature of XXB750 and the sustained pharmacological effects on BP at higher doses. The 10-day safety monitoring for the sentinel cohort is considered sufficient based on the predicted mean Tmax (4.5 days) in humans.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male and female participants age 18 to 50 years of age included, and in good health as determined by past medical history, physical examination, vital signs, electrocardiogram, and laboratory tests at screening.
- •Participants must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 - 32 kg/m
- •BMI = Body weight (kg) / [Height (m)]2
- •For ethnic Japanese cohort: participants must be defined as being of first, second or third generation ethnic origin, with each set of parents qualifying as Japanese under the prior generation.
排除标准
- •Any surgical or medical condition which significantly altered the distribution, metabolism, or excretion of drugs, or which jeopardized the participant's participation in the study.
- •Known history or current clinically significant arrhythmias.
- •Women of child-bearing potential were excluded from this study.
研究组 & 干预措施
XXB750 s.c 120 mg
Single SC dose of XXB750 120 mg
干预措施: XXB750 (Drug)
XXB750 s.c 1 mg
Single SC dose of XXB750 1 mg
干预措施: XXB750 (Drug)
XXB750 s.c 3 mg
Single SC dose of XXB750 3 mg
干预措施: XXB750 (Drug)
XXB750 s.c 10 mg
Single SC dose of XXB750 10 mg
干预措施: XXB750 (Drug)
XXB750 s.c 30 mg
Single SC dose of XXB750 30 mg
干预措施: XXB750 (Drug)
XXB750 s.c 60 mg
Single SC dose of XXB750 60 mg
干预措施: XXB750 (Drug)
XXB750 s.c 240 mg
Single SC dose of XXB750 240 mg
干预措施: XXB750 (Drug)
Placebo
Placebo to XXB750
干预措施: Placebo (Other)
XXB750 s.c 240 mg Japanese cohort
Single SC dose of XXB750 240 mg in the Japanese cohort
干预措施: XXB750 (Drug)
Placebo for Japanese cohort
Placebo to XXB750 in the Japanese cohort
干预措施: Placebo (Other)
XXB750 s.c 450 mg (HBP)
Single SC dose of XXB750 450 mg (High Blood Pressure Cohort)
干预措施: XXB750 (Drug)
XXB750 s.c 600 mg (HBP)
Single SC dose of XXB750 600 mg (High Blood Pressure Cohort)
干预措施: XXB750 (Drug)
Placebo to High Blood Pressure cohort
Placebo to XXB750 in High Blood Pressure cohorts
干预措施: Placebo (Other)
结局指标
主要结局
Number of participants with Adverse Events
时间窗: Up to 121 days
To evaluate the safety and tolerability of single ascending SC doses of XXB750 in healthy participants. Adverse events may include abnormal vital signs, safety laboratory tests, physical exam tests and ECG parameters that include clinical signs or symptoms, are considered clinically significant or require therapy.
次要结局
- Pharmacokinetics parameters: Vz/F(Up to 91 days)
- Pharmacokinetics parameters: Tmax(Up to 91 days)
- Pharmacokinetics parameters: Cmax(Up to 91 days)
- Pharmacokinetics parameters: AUClast(Up to 91 days)
- Pharmacokinetics parameters: AUCinf(Up to 91 days)
- Pharmacokinetics parameters: T1/2(Up to 91 days)
- Pharmacokinetics parameters: CL/F(Up to 91 days)