A Randomized, Double-blind, Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MET233 in Otherwise Healthy Adult Participants With Obesity or Overweight
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 144
- 试验地点
- 1
- 主要终点
- Occurrence of Treatment Emergent Adverse Events
研究概览
简要总结
The goal of this clinical trial is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of once-weekly subcutaneous injections of MET233 in otherwise healthy adults with overweight or obesity.
This study will be conducted in four parts:
- Part A will evaluate single ascending doses of MET233 or placebo.
- Part B will evaluate multiple ascending doses, with participants receiving five once-weekly doses of MET233 or placebo.
- Part C will evaluate once-weekly dosing of MET233 or placebo for 12 weeks, followed by a single higher, potential monthly dose.
- Part D will evaluate a longer dosing schedule, in which participants will receive twelve once-weekly doses, followed by three monthly doses of MET233 or placebo. Participants in this part will be followed for 14 weeks after the final dose.
详细描述
This is a randomized, placebo-controlled, double-blind study designed to investigate the safety, tolerability, PK and pharmacodynamic (PD) of single and multiple ascending subcutaneous (SC) doses of MET233 in otherwise healthy adult participants with obesity or overweight (body mass index [BMI] 27.0 kg/m2 to 38.0 kg/m2, inclusive for Parts A-C and BMI in Part D 30- 45.0 kg/m2 (inclusive).
- In Part A, participants will receive a single dose of MET233 at up to five dose levels.
- In Part B, participants will receive five weekly doses of MET233 at up to four dose levels.
- In Part C, participants will receive 12 weekly doses of MET233. These doses may include titration. For all cohorts in Part C, a 13th dose administered on Day 85 may be a monthly-equivalent dose to evaluate the potential for switching to a monthly dosing regimen.
- In Part D, participants will receive 12 once-weekly doses, followed by three monthly doses of MET233 or placebo.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Adult (≥18 to ≤70 years) male and female participants with obesity or overweight (BMI 27.0 kg/m2 to 38.0 kg/m2, inclusive) but otherwise healthy.
排除标准
- •Female who is lactating or who is pregnant according to the pregnancy test at the Screening visit or prior to the first study drug administration
- •Seated blood pressure higher than 160/95 mmHg at the Screening visit
- •Elevated resting pulse greater than 100 beats per minute at Screening visit
- •Presence of clinically significant ECG abnormalities
- •Diagnosis of diabetes (type 1 or type 2)
- •Participation in a weight loss program with or without pharmacotherapy during the 3 months prior to study administration
- •Obesity induced by endocrinologic disorders (e.g., Cushing's syndrome) or diagnosed monogenetic or syndromic forms of obesity (e.g., Melanocortin 4 Receptor deficiency or Prader-Willi Syndrome).
研究组 & 干预措施
(Part B) MET233
Participants will receive five weekly doses of MET233 at up to 4 dose levels
干预措施: MET233 (Biological)
(Part A) MET233
Participants will receive a single dose of MET233 at up to 5 dose levels
干预措施: MET233 (Biological)
(Part A) Placebo
Participants will receive a single dose of placebo
干预措施: Placebo (Biological)
(Part D) MET233
Participants will receive twelve weekly doses of MET233, followed by three monthly doses.
干预措施: MET233 (Biological)
(Part D) Placebo
Participants will receive twelve weekly doses of placebo, followed by three monthly doses.
干预措施: Placebo (Biological)
(Part B) Placebo
Participants will receive five weekly doses of placebo
干预措施: Placebo (Biological)
(Part C) MET233
Participants will receive twelve weekly doses of MET233 at up to 4 dose levels, followed by a 13th potential monthly dose
干预措施: MET233 (Biological)
(Part C) Placebo
Participants will receive twelve weekly doses of placebo, followed by a 13th potential monthly dose
干预措施: Placebo (Biological)
结局指标
主要结局
Occurrence of Treatment Emergent Adverse Events
时间窗: Part A (Baseline to Day 85), Part B (Baseline to Day 113), Part C (Baseline to Day 162), Part D (Baseline to Day 239)
次要结局
- Area under the concentration versus time curve extrapolated to infinity (AUCinf)(Part A (Baseline to Day 85))
- Area under the concentration versus time curve during the dosing interval (AUCtau)(Part B (Baseline to Day 113), Part C (Baseline to Day 162), Part D (Baseline to Day 239))
- Maximum observed concentration (Cmax)(Part A (Baseline to Day 85), Part B (Baseline to Day 113), Part C (Baseline to Day 162), Part D (Baseline to Day 239))
- Time to maximum observed concentration (Tmax)(Part A (Baseline to Day 85), Part B (Baseline to Day 113), Part C (Baseline to Day 162), Part D (Baseline to Day 239))
- Elimination half-life (t1/2)(Part A (Baseline to Day 85), Part B (Baseline to Day 113), Part C (Baseline to Day 162), Part D (Baseline to Day 239))
- Percent change from baseline in body weight at the protocol-specified weekly post-baseline measurements(Part A (Baseline to Day 85), Part B (Baseline to Day 113), Part C (Baseline to Day 162), Part D (Baseline to Day 239))