A Randomized, Double-blind, Placebo-controlled, Sequential Single and Multiple Ascending Dose (SAD/MAD) Study Following Oral Administration in Healthy Subjects to Evaluate the Safety, Tolerability, and Pharmacokinetics of ZM-H1505R
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 64
- 试验地点
- 1
- 主要终点
- Number of Participants With Clinically Significant Laboratory Findings
研究概览
简要总结
ZM-H1505R is an investigational drug developed by Shanghai Zhimeng Biopharma Inc. for the treatment of Chronic Hepatitis B.
The purpose of this study is to see how safe the study drug is and how well it is tolerated after dosing. The study will also test how the study drug is taken up and eliminated by the body. An additional part of the study is to look at how this could be changed by giving the study drug with food.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Are capable of giving informed consent and complying with study procedures;
- •Are between the ages of 18 and 55 years, inclusive;
- •Female subjects have a negative pregnancy test results at screening and Day -1, and meet one of the following criteria:
- •Using a medically acceptable form of birth control for at least 1 month prior to screening (3 months on oral contraceptives) [e.g., hormonal contraceptives (oral, patch, injectable or vaginal ring), implantable device (implantable rod or intrauterine device), or a double barrier (e.g., diaphragm, cervical cap, oral, patch or vaginal hormonal contraceptive, condom, spermicide, or sponge)]
- •Surgically sterile for at least 3 months prior to screening by one of the following means:
- •Bilateral tubal ligation
- •Bilateral salpingectomy (with or without oophorectomy)
- •Surgical hysterectomy
- •Bilateral oophorectomy (with or without hysterectomy)
- •Postmenopausal, defined as the following:
- •Last menstrual period greater than 12 months prior to screening
- •Postmenopausal status confirmed by serum FSH and estradiol levels at screening;
- •Considered healthy by the Investigator, based on subject's reported medical history, full PE, clinical laboratory tests, 12-lead ECG, and vital signs;
- •Normal liver function (AST/ALT < 1.5x ULN) and normal renal function (eGFR> 60mL/min/1.73 m2) as determined by Investigator following review of clinical laboratory test results;
- •Non-smoker and no nicotine containing products (including e-cigarettes) within 6 months;
- •Body mass index (BMI) of 18.0 to 32.0 kg/m2 inclusive and body weight not less than 50 kg;
- •Willing and able to adhere to study restrictions and to be confined at the clinical research center.
- •Male subjects with female partners of child bearing potential must agree to use condoms for the duration of the study and until 12 weeks after dosing with the study drug and must refrain from donating sperm for this same period.
排除标准
- •Clinically significant history of gastrointestinal, cardiovascular, musculoskeletal, endocrine, hematologic, psychiatric, renal, hepatic, bronchopulmonary, neurologic, immunologic, lipid metabolism disorders, or drug hypersensitivity as determined by the Investigator;
- •Reported or suspected malignancy;
- •Reported history of pancreatitis or gall stones;
- •Reported history of unexplained syncope, symptomatic hypotension or hypoglycemia;
- •Reported family history of long QTc syndrome;
- •Reported history of chronic diarrhea, malabsorption, unexplained weight loss, food allergies or intolerance;
- •Poor venous access;
- •Positive blood screen for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), or hepatitis C antibody;
- •Donated or lost >500ml of blood in the previous 3 months;
- •Taken an investigational drug or participated in a clinical trial within 3 months (or 5 half-lives), whichever is longer;
- •Taken any prescription medications within 14 days or 5 half-lives (whichever is longer) of the first dose of study drug;
- •Hospital admission or major surgery within 6 months prior to screening;
- •A reported history of prescription drug abuse, or illicit drug use within 9 months prior to screening;
- •A reported history of alcohol abuse according to medical history within 9 months prior to screening;
- •A positive screen for alcohol, drugs of abuse at screening or Day -1;
- •An unwillingness or inability to comply with food and beverage restrictions during study participation;
- •Use of over-the-counter (OTC) medication within 7 days, and herbal supplements (including St John's Wort, herbal teas, garlic extracts) within 7 days prior to dosing (Note: Use of acetaminophen at < 2 g/day is permitted until 24 hours prior to dosing)
- •Any condition or finding that in the Investigators opinion would put the subject or study conduct at risk if the subject were to participate in the study.
研究组 & 干预措施
Cohort 1 of Part 1 (SAD)
300 mg ZM-H1505R or placebo
干预措施: ZM-H1505R (Drug)
Cohort 2 of Part 1(SAD)
450 mg ZM-H1505R or placebo
干预措施: ZM-H1505R (Drug)
Cohort 3 of Part 1(SAD)
150 mg ZM-H1505R or placebo (2 periods)
干预措施: ZM-H1505R (Drug)
Cohort 4 of Part 1(SAD)
75 mg ZM-H1505R or placebo
干预措施: ZM-H1505R (Drug)
Cohort 5 of Part 1(SAD)
25 mg ZM-H1505R or placebo
干预措施: ZM-H1505R (Drug)
Cohort 1 of Part 2 (MAD)
75 mg ZM-H1505R or placebo
干预措施: ZM-H1505R (Drug)
Cohort 2 of Part 2 (MAD)
150 mg ZM-H1505R or placebo
干预措施: ZM-H1505R (Drug)
Cohort 3 of Part 2 (MAD)
300 mg ZM-H1505R or placebo
干预措施: ZM-H1505R (Drug)
结局指标
主要结局
Number of Participants With Clinically Significant Laboratory Findings
时间窗: 22 days for Cohorts 1, 2, 4, and 5; 36 days for Cohort 3 in part 1 and Chorts in part 2
Safety data from subjects in Part 1 and Part 2 treated with placebo will be pooled, respectively. Safety evaluations will be based on the incidence, intensity, and relatedness of AEs and changes in subject clinical laboratory results
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events
时间窗: 22 days for Cohorts 1, 2, 4, and 5; 36 days for Cohort 3 in part 1 and Chorts in part 2
Safety data from subjects in Part 1 and Part 2 treated with placebo will be pooled, respectively. Safety evaluations will be based on the incidence, intensity, and relatedness of AEs
Number of Participants With Abnormal Physical Examinations
时间窗: 22 days for Cohorts 1, 2, 4, and 5; 36 days for Cohort 3 in part 1 and Chorts in part 2
Safety data from subjects in Part 1 and Part 2 treated with placebo will be pooled, respectively. Safety evaluations will be based on the incidence, intensity, and relatedness of AEs and changes in subject PE findings
Number of Participants With Abnormal Vital Signs
时间窗: 22 days for Cohorts 1, 2, 4, and 5; 36 days for Cohort 3 in part 1 and Chorts in part 2
Safety data from subjects in Part 1 and Part 2 treated with placebo will be pooled, respectively. Safety evaluations will be based on the incidence, intensity, and relatedness of AEs and changes in subject vital signs
Number of Participants With Abnormal ECGs
时间窗: 22 days for Cohorts 1, 2, 4, and 5; 36 days for Cohort 3 in part 1 and Chorts in part 2
Safety data from subjects in Part 1 and Part 2 treated with placebo will be pooled, respectively. Safety evaluations will be based on the incidence, intensity, and relatedness of AEs and changes in subject ECGs.
次要结局
未报告次要终点