A Randomized, Double-blind, Placebo-controlled, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of ZT006 as Well as the Food Effect on the Pharmacokinetics of ZT006 in Healthy, Overweight and Obese Participants
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 94
- 试验地点
- 1
- 主要终点
- Rate of treatment-emergent adverse events after single dose administration under fasted condition.
研究概览
简要总结
ZT006 is an oral, long-acting glucagon-like peptide-1. This first-in-human study is designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of ZT006 in healthy, overweight and obese participants. The study comprises three parts, i.e. single dose-escalation, multiple dose-escalation, food effect on the pharmacokinetics of ZT006.
In the single dose-escalation study, participants will receive a single dose (ZT006 dose level 1 - 5 or corresponding placebo) of ZT006 under fasted condition. A higher dose can only be given after obtaining acceptable safety and tolerability data for at least 7 days after the previous dose. After study drug administration, there will be a 7-day in-house period for safety observation and pharmacokinetics samples collection. Participants will join ambulatory visits until 42 days post-dose.
In the multiple dose-escalation study, participants will receive a daily dose of ZT006 or corresponding placebo over 42 days in a dose up-titration fashion according to the following regimen:
- Cohort 1: dose level 1 - dose level 2 - dose level 3
- Cohort 2: dose level 1 - dose level 2 - dose level 3 - dose level 4
- Cohort 3: dose level 2 - dose level 3 - dose level 4
- Cohort 4: dose level 2 - dose level 3 - dose level 4 - dose level 5
Dosing of a cohort with higher drug exposure can only be done after evaluation of safety and tolerability data for at least 14 days after the first dose in the previous cohort. Participants will join ambulatory visits until 35 days after the last dose.
To evaluate the food effect on the pharmacokinetics of ZT006, participants who have received single dose of ZT006 or placebo of dose level 4 in the single dose-escalation study will receive another dose of ZT006 or placebo after a high fat, high caloric breakfast.
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 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, 12-lead electrocardiogram and clinical laboratory tests (hematology, urinalysis, chemistry, coagulation), as judged by the investigator.
- •Male or female, age between 18 - 55 years (both inclusive) at the time of signing of the informed consent.
- •Body mass index (BMI) 19.0 - 35.0 kg/m²(both inclusive). Body weight >50.0 kg for male participants and >45.0 kg for female participants. BMI 19 - 28.0 kg/m²(both inclusive) for single-dose escalation study, BMI 19.0 - 28.0 kg/m²(both inclusive) for cohorts 1 and 2 of multiple-dose escalation study, BMI 24.0 - 35.0 kg/m²(both inclusive) for cohorts 3 and 4 of multiple-dose escalation study.
- •Having dietary caloric restriction and increased physical activity for ≥3 months, with change in body weight (increase or decrease) no more than 5%, irrespective of medical records.
排除标准
- •Known hypersensitivity to the study drug or excipients or GLP-1 receptor agonists.
- •Medical history of hypoglycemia.
- •History or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2, or history of pancreatitis or symptomatic gallbladder disease.
- •Previous diagnosis of endocrine disorders or monogenic mutations causing obesity, including but not limited to hypothalamic obesity, pituitary obesity, hypothyroidism-induced obesity, Cushing's syndrome, insulinoma, acromegaly, or hypogonadism.
- •Use of GLP-1 receptor agonists within 30 days or 5 half-lives (whichever is longer) before the first dose of the investigational intervention.
- •Glycated hemoglobin (HbA1c) > 6.0% or fasting plasma glucose < 3.9 mmol/L or > 6.1 mmol/L at screening, or diagnosed with diabetes mellitus of type 1 or type 2 diabetes or other specific types derived from other causes.
- •Aspartate aminotransferase ≥ 2 × upper limit of normal (ULN), Alanine aminotransferase ≥ 2 × ULN, or total bilirubin ≥ 1.5 × ULN
- •Calcitonin above ULN at screening.
- •Other clinically significant diseases detected within 12 months before screening (including but not limited to gastrointestinal, renal, hepatic, neurological, hematological, endocrine, oncological, pulmonary, immunological, psychiatric, or cardiovascular diseases).
- •Use of prescription drugs (excluding topical eye/nose drops and creams without systemic exposure risk), over-the-counter drugs, dietary supplements, vitamins, or herbal medicines (excluding routine vitamins) within 2 weeks before screening.
- •Long-term use of medications directly affecting gastrointestinal motility prior to screening. Use of weight-loss medications (including but not limited to orlistat) within 3 months before dosing.
研究组 & 干预措施
ZT006 tablet, multiple doses, cohort 1
干预措施: ZT006 (Drug)
ZT006 tablet, dose level 1, single dose, fasted
干预措施: ZT006 (Drug)
ZT006 tablet, dose level 2, single dose, fasted
干预措施: ZT006 (Drug)
ZT006 tablet, dose level 3, single dose, fasted
干预措施: ZT006 (Drug)
ZT006 tablet, dose level 4, single dose, fasted and fed
干预措施: ZT006 (Drug)
ZT006 tablet, dose level 5, single dose, fasted
干预措施: ZT006 (Drug)
ZT006 tablet, multiple doses, cohort 2
干预措施: ZT006 (Drug)
ZT006 tablet, multiple doses, cohort 3
干预措施: ZT006 (Drug)
ZT006 tablet, multiple doses, cohort 4
干预措施: ZT006 (Drug)
placebo of ZT006, single dose, fasted
干预措施: Placebo of ZT006 (Drug)
placebo of ZT006, single dose, fasted and fed
干预措施: Placebo of ZT006 (Drug)
placebo of ZT006, multiple doses
干预措施: Placebo of ZT006 (Drug)
结局指标
主要结局
Rate of treatment-emergent adverse events after single dose administration under fasted condition.
时间窗: From baseline to Day 43
Summarized from adverse event reporting in %
Rate of treatment-emergent adverse events during and after multiple-dose administration.
时间窗: From baseline to end of study (Day 77)
Summarized from adverse event reporting in %
Rate of treatment-emergent adverse events after single dose administration under fed condition.
时间窗: From Day 44 to end of study (Day 86)
Summarized from adverse event reporting in %
次要结局
- Incidence of ZT006 anti-drug antibody after single-dose administration under fasted condition.(From baseline to Day 43)
- Incidence of ZT006 anti-drug antibody during and after multiple-dose administration.(From baseline to end of study (Day 77))
- Area under the concentration-time curve from time zero to infinity after single-dose administration under fasted condition.(From baseline to Day 43)
- Area under the concentration-time curve during the dosing interval at steady state.(Day 42 to Day 77)
- Terminal half-life after single-dose administration under fed condition.(From Day 44 to end of study (Day 86))
- Maximal observed concentration after single-dose administration under fasted condition.(From baseline to Day 43)
- Maximal observed concentration at steady state.(Day 42 to Day 77)
- Time to reach the maximal observed concentration after single-dose administration under fasted condition.(From baseline to Day 43)
- Terminal half-life after single-dose administration under fasted condition.(From baseline to Day 43)
- Time to reach the maximal observed concentration at steady state.(From Day 42 to Day 77)
- Terminal half-life at steady state.(From Day 42 to Day 77)
- Area under the concentration-time curve from time zero to infinity after single-dose administration under fed condition.(From Day 44 to end of study (Day 86))
- Maximal observed concentration after single-dose administration under fed condition.(From Day 44 to end of study (Day 86))
- Time to reach the maximal observed concentration after single-dose administration under fed condition.(From Day 44 to end of study (Day 86))