A Randomised, Double-Blind, Placebo-Controlled, First-in-Human Study of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Doses of ZE46-0134 in Healthy Volunteers
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 112
- 试验地点
- 1
- 主要终点
- Plasma concentration
研究概览
简要总结
This is a clinical study aiming to assess pharmacokinetics and biomarker evidence of ZE46-0134 efficacy in Healthy Volunteers after single and multiple daily doses of the study drug
详细描述
This is a Phase 1, double-blind, placebo-controlled, dose escalation study to evaluate the safety, tolerability, PK, PD of orally administered ZE46-0134 in Healthy Volunteers. The study will be conducted in 2 parts: a single ascending dose (SAD) part at up to 6 dose levels and a multiple ascending dose (MAD) part at up to 5 dose levels. Evaluation of dose levels will be conducted in a sequential fashion with lower dose levels evaluated first in the sequence. Dosing in each cohort will start with two sentinel participants with one of the two sentinels randomised to receive ZE46-0134 and the other randomised to receive placebo. The food-effect will be investigated in SAD part and safety/PK of co-administration with rabeprazole will be investigated in MAD part.
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
- Double (Participant, Investigator)
盲法说明
Double-Blind, Placebo-Controlled
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
- •1. Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the trial, including possible risks and adverse effects.
- •2. Adult males and females, 18 to 55 years of age (inclusive) at screening.
- •Body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2, with a body weight (to 1 decimal place) ≥ 50.0 kg at screening.
- •4. Medically healthy without clinically significant abnormalities (in the opinion of the Investigator) at the screening visit and prior to dosing
排除标准
- •History or presence of significant cardiovascular, pulmonary, hepatic, renal, haematological, gastrointestinal, endocrine, immunologic, dermatologic or neurological disease, including any acute illness or major surgery within the past 3 months determined by the PI to be clinically significant.
- •Acute infections within 4 weeks prior to screening or current infection that requires systemically absorbed antibiotic, antifungal, antiparasitic or antiviral medications.
- •Presence or history of any abnormality or illness, including gastrointestinal surgery, which in the opinion of the PI may affect absorption, distribution, metabolism or elimination of the study drug.
- •Any history of malignant disease in the last 5 years (excludes surgically resected skin squamous cell or basal cell carcinoma).
- •Any screening laboratory result outside the normal laboratory reference range (as confirmed upon repeated testing) and deemed clinically significant by the PI.
- •Presence of clinically relevant immunosuppression from, but not limited to, immunodeficiency conditions such as common variable hypogammaglobulinemia
研究组 & 干预措施
Level 1 Single dose
Dose level 1. SAD study part. 6 participants will receive the study drug and 2 participants will receive placebo
干预措施: ZE46-0134 or placebo (Drug)
Level 2 Single dose
Dose level 2. SAD study part. 6 participants will receive the study drug and 2 participants will receive placebo
干预措施: ZE46-0134 or placebo (Drug)
Level 3 Single dose
Dose level 3. SAD study part. 6 participants will receive the study drug and 2 participants will receive placebo
干预措施: ZE46-0134 or placebo (Drug)
Level 2 Single dose after food
Dose level 2 with a fat meal. SAD study part. 6 participants will receive the study drug and 2 participants will receive placebo
干预措施: ZE46-0134 or placebo (Drug)
Level 4 Single dose
Dose level 4. SAD study part. 6 participants will receive the study drug and 2 participants will receive placebo
干预措施: ZE46-0134 or placebo (Drug)
Level 1 Multiple doses
Dose level 1. MAD study part. 6 participants will receive the study drug and 2 participants will receive placebo
干预措施: ZE46-0134 or placebo (Drug)
Level 1 Multiple doses + rabeprazole
Dose level 2. MAD study part. 6 participants will receive the study drug and 2 participants will receive placebo. The drug is co-administered with rabeprazole
干预措施: ZE46-0134 or placebo (Drug)
Level 1 Multiple doses + rabeprazole
Dose level 2. MAD study part. 6 participants will receive the study drug and 2 participants will receive placebo. The drug is co-administered with rabeprazole
干预措施: Rabeprazole, 20mg oral (Drug)
Level 2 Multiple doses
Dose level 2. MAD study part. 6 participants will receive the study drug and 2 participants will receive placebo
干预措施: ZE46-0134 or placebo (Drug)
Level 3 Single dose with itraconazole
Dose level 3. SAD study part. 6 participants will receive the study drug and 2 participants will receive placebo, in conjunction with itraconazole
干预措施: ZE46-0134 or placebo (Drug)
Level 3 Single dose with itraconazole
Dose level 3. SAD study part. 6 participants will receive the study drug and 2 participants will receive placebo, in conjunction with itraconazole
干预措施: Itraconazole (200 mg) (Drug)
Level 5 Single dose
Dose level 5. SAD study part. 6 participants will receive the study drug and 2 participants will receive placebo
干预措施: ZE46-0134 or placebo (Drug)
Level 6 Single dose
Dose level 6. SAD study part. 6 participants will receive the study drug and 2 participants will receive placebo
干预措施: ZE46-0134 or placebo (Drug)
Level 3 Multiple doses
Dose level 3. MAD study part. 6 participants will receive the study drug and 2 participants will receive placebo
干预措施: ZE46-0134 or placebo (Drug)
Level 4 Multiple doses
Dose level 4. MAD study part. 6 participants will receive the study drug and 2 participants will receive placebo
干预措施: ZE46-0134 or placebo (Drug)
Level 5 Multiple doses
Dose level 5. MAD study part. 6 participants will receive the study drug and 2 participants will receive placebo
干预措施: ZE46-0134 or placebo (Drug)
结局指标
主要结局
Plasma concentration
时间窗: 72 hours for SAD, 10 days for MAD
Plasma concentration, ng/mL
次要结局
- Incidence of drug-related AEs(8 days in SAD part, 17 days for MAD part)
- Incidence of AEs(8 days in SAD part, 17 days for MAD part)
- Incidence of SAEs(8 days in SAD part, 17 days for MAD part)
- Incidence of lab deviations(Time Frame: 8 days in SAD part, 17 days for MAD part)