A Phase 2, Parallel-Group, Double-Blind, 4-Arm Study to Investigate Weight Management With LY3305677 Compared With Placebo and in Adult Participants With Obesity or Overweight
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 179
- 试验地点
- 58
- 主要终点
- Percent Change From Baseline in Body Weight at Week 32
研究概览
简要总结
The main purpose of this study, performed under a master protocol W8M-MC-CWMM (NCT06143956), is to investigate weight management efficacy and safety with Mazdutide compared with placebo and in adult participants with obesity or overweight. The study will last about 62 weeks.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •W8M-MC-OXA1:
- •Are males and females who agree to abide by the reproductive and contraceptive requirements
- •W8M-MC-CWMM:
- •Have a BMI ≥27 kilograms per square meter (kg/m²)
排除标准
- •W8M-MC-OXA1:
- •Have any prior diagnosis of diabetes mellitus, that is type 2 diabetes mellitus (T2DM), or rare forms of diabetes mellitus, except gestational diabetes.
- •Have any of the following cardiovascular conditions within 6 months prior to screening:
- •acute myocardial infarction
- •cerebrovascular accident (stroke)
- •unstable angina, or
- •hospitalization due to congestive heart failure (CHF).
- •Have a history of New York Heart Association (NYHA) Functional Classification I-IV CHF.
- •Participants with hypertension who do not have well-controlled blood pressure (BP) (>140/90 mmHg), regardless of antihypertensive treatment. Participants receiving treatment for hypertension should be on a stable antihypertensive regimen for at least 3 months prior to screening.
- •Have a history of acute or chronic pancreatitis.
- •Note: If the investigator anticipates a need to add antihypertensive medication during the study, the participant should not be included in the ambulatory blood pressure monitoring (ABPM) procedures.
- •Have a prior or planned surgical treatment for obesity, except prior liposuction or abdominoplasty, if performed >1 year prior to screening.
- •Have type 1 diabetes mellitus, latent autoimmune diabetes in adults, or history of ketoacidosis or hyperosmolar coma.
- •Have poorly controlled hypertension.
- •Have signs and symptoms of any liver disease other than nonalcoholic fatty liver disease.
- •Have a history of symptomatic gallbladder disease within the past 2 years.
- •Have a lifetime history of suicide attempts.
研究组 & 干预措施
16 mg Mazdutide
Participants received once-weekly subcutaneous Mazdutide with dose escalation until the target dose (16 mg) was achieved, starting at 1.5 mg from Weeks 0-3, followed by 3 mg from Weeks 4-7, 6 mg from Weeks 8-11, 9 mg from Weeks 12-15, 12 mg from Weeks 16-19, and then16 mg from Weeks 20-48.
干预措施: Mazdutide (Drug)
3/6 Milligrams (mg) Mazdutide
Participants received once-weekly subcutaneous Mazdutide with dose escalation until the target dose (3 or 6 mg) was achieved, starting at 1.5 mg from Weeks 0-3, followed by 3 mg from Weeks 4-31, then 6 mg from Weeks 32-48.
干预措施: Mazdutide (Drug)
10 mg Mazdutide
Participants received once-weekly subcutaneous Mazdutide with dose escalation until the target dose (10 mg) was achieved, starting at 1.5 mg from Weeks 0-3, followed by 3 mg from Weeks 4-7, 6 mg from Weeks 8-11, 8 mg from Weeks 12-15, and then 10 mg from Weeks 16-48.
干预措施: Mazdutide (Drug)
Placebo
Participants received Mazdutide matched placebo subcutaneously once weekly from Weeks 0 to 48.
干预措施: Placebo (Drug)
结局指标
主要结局
Percent Change From Baseline in Body Weight at Week 32
时间窗: Baseline, Week 32
Least squares means were calculated using an MMRM model for post-baseline measures: Variable = Baseline\*Time + Strata\*Time + Treatment\*Time, where Treatment and Strata are factors. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. Strata is defined by joint levels of Sex and Baseline BMI (\<=30, \>30 kg/m\^2).
Percent Change from Baseline in Body Weight
时间窗: Baseline to Week 32
次要结局
- Percent Change From Baseline in Body Weight at Week 48(Baseline, Week 48)
- Change From Baseline in Body Weight(Baseline, Week 32, Week 48)
- Mean Percentage of Participants Who Achieve ≥5% Body Weight Reduction(Baseline, Week 32, Week 48)
- Mean Percentage of Participants Who Achieve ≥10% Body Weight Reduction(Baseline, Week 32, Week 48)
- Change From Baseline in Body Mass Index (BMI)(Baseline, Week 32, Week 48)
- Number of Participants With Treatment Emergent Anti-drug Antibodies (TE-ADAs)(Baseline up to week 56)
- Pharmacokinetics (PK): Area Under the Curve (AUC) of Mazdutide at Steady State(Predose at Week 0, Week 4, Week 8, Week 12, Week 24, Week 32, Week 48; Post dose (2 to 6 hours after dosing) at Week 0, Week 12, Week 24)
- PK: Maximum Concentration (Cmax) of Mazdutide at Steady State(Predose at Week 0, Week 4, Week 8, Week 12, Week 24, Week 32, Week 48; Post dose (2 to 6 hours after dosing) at Week 0, Week 12, Week 24)
- Change From Baseline in Liver Fat Content (LFC) by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) in Participants With Baseline LFC >=5%(Baseline, Week 32, Week 48)
- Percent Change From Baseline in Liver Fat Content by MRI-PDFF in Participants With Baseline LFC >=5%(Baseline, Week 32, Week 48)
- Change From Baseline in Liver Fat Content by MRI-PDFF in Participants With Baseline LFC >=10%(Baseline, Week 32, Week 48)
- Percent Change From Baseline in Liver Fat Content by MRI-PDFF in Participants With Baseline LFC >=10%(Baseline, Week 32, Week 48)
- Mean Percentage of Participants With Baseline Liver Fat Content (LFC) >= 5% Who Achieved >30% Relative Reduction in LFC(Baseline, Week 32, Week 48)
- Mean Percentage of Participants With Baseline Liver Fat Content (LFC) >=10% Who Achieved >30% Relative Reduction in LFC(Baseline, Week 32, Week 48)
- Change from Baseline in Body Weight(Baseline, Week 48)
- Pharmacokinetics (PK): Area Under the Curve (AUC) of LY3305677(Baseline to Week 56)
- Absolute Change from Baseline in Liver Fat Content by MRI-PDFF in Participants with Baseline LFC ≥5% and Baseline LFC≥10%(Baseline to Week 48)
- Percent Change from Baseline in Liver Fat Content by MRI-PDFF in Participants with Baseline LFC ≥5% and Baseline LFC≥10%(Baseline, Week 48)
- Percent Change from Baseline in Body Weight(Baseline, Week 48)
- PK: Maximum Concentration (Cmax) of LY3305677(Baseline to Week 56)
- Percentage of Participants Who Achieve ≥5% Body Weight Reduction(Baseline to Week 48)
- Percentage of Participants Who Achieve ≥10% Body Weight Reduction(Baseline to Week 48)
- Change from Baseline in Body Mass Index (BMI)(Baseline to Week 32)
- Change from Baseline in BMI(Baseline to Week 48)
- Number of Participants with Treatment Emergent Drug Antibodies (TE-ADAs)(Baseline to Week 56)
- Absolute Change from Baseline in Liver Fat Content (LFC) by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) in Participants with Baseline LFC≥5% and Baseline LFC≥10%(Baseline to Week 32)
- Percent Change from Baseline in Liver Fat Content by MRI-PDFF in Participants with Baseline LFC≥5% and Baseline LFC≥10%(Baseline to Week 32)
- Percentage of Participants Who Achieve ≥30% Relative Reduction in LFC(Baseline to Week 32)
- Percentage of Participants Who Achieve >30% Relative Reduction in LFC(Baseline to Week 48)