A First-in-human, Double-blind, Placebo-controlled, Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Intravenous Doses of HM201 (Pegylated Human Adrenomedullin) in Healthy Subjects (Adults)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 53
- 试验地点
- 1
- 主要终点
- Number and percentage of treatment-emergent adverse event, serious adverse event and discontinuation.
研究概览
简要总结
This will be a single centre, Phase 1, Placebo-controlled, Randomized, Doubleblind, SAD & MAD Study to Assess the Safety, Tolerability and PK of HM201 in Healthy Subjects.
详细描述
Objective of the study is to assess the safety, tolerability, and PK of single and multiple intravenous administration of HM201. The study design consists of a SAD study of 4 cohorts, 8 subjects each cohort and a different dose level per cohort. In each cohort 2 will receive the placebo while rest of group will be administered with HM201. A total of 32 subjects are planned for the SAD study.
MAD part will begin after cohort 1 and 2 of SAD is completed. MAD will consist of 8 subjects; 2 will receive the placebo while 6 will be administered with HM201. MAD will be conducted in a dose escalation manner with 4 weekly doses administered to all subjects. One randomization scheme will be produced for each cohort separately.
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)
盲法说明
This study will be conducted as a double-blind study. All subjects and clinical personnel will involved in the collection, monitoring, revision, safety and adverse events will be blinded in regards to the subject's treatment assigned of HM201 or the HM201 placebo. All personnel affecting the outcome of the study's treatment assignment will be blinded.
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male or non-childbearing potential female
- •BMI ≥18.0 and ≤32.0 kg/m2
- •Good health based on past medical history, medication use, vital signs and physical exam.
- •Normal renal and hepatic function.
- •Female partners of child bearing potential must agree to use contraception.
排除标准
- •Clinically significant medical history.
- •Significant drug allergy.
- •Use of experimental drug within 3 months prior.
- •Previously received HM201, AM and other derivatives.
- •History of old myocardial infarction.
- •Diagnosed with malignant tumor or history of treatment for malignant tumor.
- •History of drug or alcohol abuse.
- •Use of omitted medicines or substance opposing objective of study.
- •COVID19 vaccine administered within 14 days of initiation of investigational product or if to receive additional dose within 30 days of investigational product administration.
- •Use of tobacco/nicotine in excess of ≥ 5 cigarettes a day and unable or unwilling to prohibit smoking during admission to site.
- •Daily consumption of more than 1L of caffeine/xanthine beverage which cannot be discontinued more than 24 hours prior to dosing of investigational product and/or ECG measurement.
- •Regular use of nutraceuticals (e.g., St. John's wort, ginseng, ginkgo biloba, Chinese herbs, and melatonin) within 1 week before administration of investigational product.
- •Donation of plasma or platelet or 200 mL of whole blood within 4 weeks or 400 mL whole blood within 3 months before administration of investigational product.
- •Clinically relevant findings in ECG.
- •Systolic blood pressure below 100 mmHg or above 140 mmHg at screening.
- •Diastolic blood pressure above 90 mmHg at screening.
- •Heart rate below 40 beats/min or above 100 beats/min at screening.
- •Symptom of orthostatic hypotension is found at screening or before investigational product administration (Day -1).
- •Hepatitis B virus surface antigen (HBsAg), hepatitis B virus core antibody (HBcAb) hepatitis C virus antibodies (anti-HCV) or human immunodeficiency virus (HIV) antigen and antibody at screening.
- •Positive to syphilis.
- •Positive to urine drug test.
- •Positive alcohol breath test.
研究组 & 干预措施
SAD Cohorts 1 to 4: Participants receiving HM201
Each SAD cohort participant will be randomized to receive 1 of 4 escalating doses (0.01 mg/kg (2 nmol/kg); 0.03 mg/kg (5 nmol/kg); 0.06 mg/kg (10 nmol/kg); 0.12 mg/kg (20 nmol/kg).
干预措施: HM201 (Drug)
SAD Cohorts 1 to 4: Participants Receiving Placebo
Each SAD cohort participant will be randomized to receive placebo.
干预措施: Placebo (Drug)
MAD Cohorts 1 to 4: Participants Receiving HM201
Each MAD cohort participant will be randomized to receive a once a week dose of 1 of 4 escalating doses (0.01 mg/kg (2 nmol/kg); 0.03 mg/kg (5 nmol/kg); 0.06 mg/kg (10 nmol/kg), 0.12 mg/kg (20 nmol/kg) for 4 weeks.
干预措施: HM201 (Drug)
MAD Cohorts 1 to 4: Participants Receiving Placebo
Each MAD cohort participant will be randomized to receive placebo once a week for 4 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Number and percentage of treatment-emergent adverse event, serious adverse event and discontinuation.
时间窗: Up to 15 days post last infusion for both SAD & MAD
次要结局
- Pharmacokinetic assessment 3(SAD: Up to Day 15. MAD: Up to Day 36)
- Plasma concentrations of HM201(SAD: Up to Day 15. MAD: Up to Day 36)
- Pharmacokinetic assessment 5(SAD: Up to Day 15. MAD: Up to Day 36)
- Pharmacokinetic assessment 1(SAD: Up to Day 15. MAD: Up to Day 36)
- Pharmacokinetic assessment 7(SAD: Up to Day 15. MAD: Up to Day 36)
- Pharmacokinetic assessment 8(SAD: Up to Day 15. MAD: Up to Day 36)
- Pharmacokinetic assessment 2(SAD: Up to Day 15. MAD: Up to Day 36)
- Pharmacokinetic assessment 4(MAD: Up to Day 36)
- Pharmacokinetic assessment 6(SAD: Up to Day 15. MAD: Up to Day 36)