A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once-Daily Oral Orforglipron Compared With Placebo in Adult Participants With Obesity or Overweight With Weight-Related Comorbidities (ATTAIN-1)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 3,127
- 试验地点
- 273
- 主要终点
- Mean Percent Change from Baseline in Body Weight
研究概览
简要总结
This study will investigate the efficacy and safety of once daily oral orforglipron in adult participants with obesity or overweight with weight-related comorbidities. The study has two phases: a main phase and an extension phase. The main phase of the study lasted 72 weeks. Participants with prediabetes will continue in the extension for another 2 years.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a BMI
- •≥30.0 kilogram/square meter (kg/m²),
- •≥27.0 kg/m² and presence of at least 1 of the following weight-related comorbidities (treated or untreated) at screening:
- •Hypertension, dyslipidemia, obstructive sleep apnea, cardiovascular disease (for example, ischemic cardiovascular disease, New York Heart Association Functional Class I-III heart failure).
- •Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight.
排除标准
- •Have Type 1 diabetes, Type 2 diabetes, or any other types of diabetes, history of ketoacidosis, or hyperosmolar state/coma
- •Have a self-reported change in body weight >5 kg (11 pounds) within 90 days prior to screening.
- •Have family (first-degree relative) or personal history of medullary thyroid cancer (MTC) or multiple endocrine neoplasia (MEN)2 syndrome.
- •Have had a history of chronic or acute pancreatitis.
研究组 & 干预措施
36 mg Orforglipron
Primary Treatment Period (Week 0-Week 72): Participants with normoglycemia or prediabetes at the time of randomization received orforglipron, administered orally QD, starting at a dose of 1 mg and escalated every 4 weeks until reaching a dose of 36 mg at week 20, which was then maintained up to week 72.
干预措施: Orforglipron (Drug)
6 mg Orforglipron
Primary Treatment Period (Week 0-Week 72): Participants with normoglycemia or prediabetes at the time of randomization received orforglipron, administered orally QD, starting at a dose of 1 milligrams (mg) and escalated every 4 weeks until reaching a dose of 6 mg at week 8, which was then maintained up to week 72.
干预措施: Orforglipron (Drug)
12 mg Orforglipron
Primary Treatment Period (Week 0-Week 72): Participants with normoglycemia or prediabetes at the time of randomization received orforglipron, administered orally QD, starting at a dose of 1 mg and escalated every 4 weeks until reaching a dose of 12 mg at week 12, which was then maintained up to week 72.
干预措施: Orforglipron (Drug)
Placebo
Primary Treatment Period (Week 0-Week 72): Participants with normoglycemia or prediabetes at the time of randomization received orforglipron-matching placebo, administered orally once daily (QD), for a period of 72 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Mean Percent Change from Baseline in Body Weight
时间窗: Baseline to Week 72
Percent Change From Baseline in Body Weight (Primary Treatment Period)
时间窗: Baseline, Week 72
Values represented under "Least Squares (LS) Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a mixed-model repeated measures (MMRM) for post-baseline measures with geographic region, baseline by time by treatment, and strata by time by treatment in the model. Strata was defined by joint levels of Sex (female, male) and prediabetes status (yes, no). Variance-covariance structure for change from baseline was unstructured.
次要结局
- Change From Baseline in Waist Circumference (Primary Treatment Period)(Baseline, Week 72)
- Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg) - Primary Treatment Period(Baseline, Week 72)
- Percent Change From Baseline in Non-High Density Lipoprotein (Non-HDL) Cholesterol (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg) - Primary Treatment Period(Baseline, Week 72)
- Percent Change From Baseline in Triglycerides (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg) - Primary Treatment Period(Baseline, Week 72)
- Change From Baseline in HbA1c (Primary Treatment Period)(Baseline, Week 72)
- Change From Baseline in Fasting Serum Glucose (FSG) (Primary Treatment Period)(Baseline, Week 72)
- Percent Change From Baseline in Fasting Insulin (Primary Treatment Period)(Baseline, Week 72)
- Change From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg) - Primary Treatment Period(Baseline, Week 72)
- Change From Baseline in Short Form-36 Health Survey Version 2 (SF-36v2) Acute Form (Physical Component and Mental Component) Scores - (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg) - Primary Treatment Period(Baseline, Week 72)
- Percent Change From Baseline in Body Weight (Primary and Additional Treatment Periods: Participants With Prediabetes at Randomization)(Baseline, Week 176)
- Time to Onset of Type 2 Diabetes (Primary and Additional Treatment Periods: Participants With Prediabetes at Randomization)(Baseline through Week 176, Baseline through Week 190)
- Mean Change from Baseline in Waist Circumference(Baseline, Week 72)
- Mean Change from Baseline in Systolic Blood Pressure (SBP)(Baseline, Week 72)
- Mean Percent Change from Baseline in Fasting non-HDL Cholesterol(Baseline, Week 72)
- Mean Percent Change from Baseline in Fasting Triglycerides(Baseline, Week 72)
- Mean Change from Baseline in Hemoglobin A1c (HbA1c) %(Baseline, Week 72)
- Mean Change from Baseline in Fasting Glucose(Baseline, Week 72)
- Mean Percent Change from Baseline in Fasting Insulin(Baseline, Week 72)
- Mean Change from Baseline in Diastolic Blood Pressure (DBP)(Baseline, Week 72)
- Mean Change from Baseline in Short Form Version 2 (SF-36v2) Acute Form Domain Scores(Baseline, Week 72)
- Mean Percent Change from Baseline in Body Weight in Participants with Prediabetes at Randomization(Baseline, Week 176)
- Time to Onset of Type 2 Diabetes(Baseline through Week 176, Baseline through Week 190)