NCT05929066已完成3 期
A Master Protocol to Investigate the Efficacy and Safety of LY3437943 Once Weekly in Participants Without Type 2 Diabetes Who Have Obesity or Overweight: A Randomized, Double-Blind, Placebo-Controlled Trial (TRIUMPH-1)
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 2,335
- 试验地点
- 266
- 主要终点
- Percent Change From Baseline in Body Weight
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of retatrutide in participants who have obesity or overweight (J1I-MC-GZBJ master protocol) including subsets of participants who have knee osteoarthritis (OA) (J1I-MC-GOA1) or who have obstructive sleep apnea (OSA) (J1I-MC-GSA1). This study will last about 89 weeks and will include up to 24 visits. Addendum (2) is optional and available to approximately 500 participants to continue treatment with retatrutide for up to an additional 24 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have body mass index (BMI) ≥30.0 kilograms per square meter (kg/m²), or ≥27.0 kg/m² with at least one of the following:
- •hypertension
- •dyslipidemia
- •obstructive sleep apnea, or
- •cardiovascular disease
- •History of at least one unsuccessful dietary effort to reduce body weight
- •GOA1 Inclusion Criteria:
- •Have index knee pain for >12 weeks prior to screening, and presence of index knee pain for >15 days over the previous month
- •Have knee X-ray with moderate radiographic changes (Kellgren-Lawrence Grade 2 or 3) per central reading at screening
- •Currently meets American College of Rheumatology (ACR) Criteria (clinical and radiological) for OA.
- •GSA1 Inclusion Criteria:
- •Previously diagnosed with OSA
- •Have AHI ≥15 on polysomnography at screening (definition of moderate-to-severe OSA)
- •For participants not on positive airway pressure (PAP) therapy: unable or unwilling to use PAP therapy and have not used PAP for at least 4 weeks prior to screening.
- •If on PAP therapy, have been on PAP therapy for at least 3 consecutive months prior to screening, and willing to temporarily stop using PAP therapy for approximately 7 days prior to each of the sleep study (PSG) visits.
- •GZBJ Addenda (2) inclusion criteria:
- •Have completed the final treatment visit of GZBJ Week 80.
排除标准
- •Have a self-reported or documented change in body weight >5 kg (11 pounds) within 90 days.
- •Have taken weight loss drugs, including over-the-counter medications, within 90 days prior to screening.
- •Have a prior or planned surgical treatment for obesity.
- •Have diabetes mellitus.
- •Have family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2)
- •Have had pancreatitis.
- •GOA1 exclusion criteria
- •Have had steroid joint injections within 90 days of screening.
- •Have had other joint injections and procedures within 6 months of screening.
- •Have joint disease other than osteoarthritis.
- •GSA1 exclusion criteria
- •Use stimulants (for example, modafinil, armodafinil, solriamfetol, pitolisant, amphetamine) less than 3 months prior to screening.
- •Use hypnotics, mirtazapine, opioids, trazodone, and zonisamide less than 3 months prior to screening.
- •Use a dental appliance or other device to treat OSA other than PAP therapy.
- •GZBJ Addenda (2) exclusion criteria
- •Have had study intervention discontinuation.
- •Have had permanent dose reduction.
研究组 & 干预措施
Retatrutide Dose 2
Experimental
Participants will receive retatrutide SC.
干预措施: Retatrutide (Drug)
Retatrutide Dose 3
Experimental
Participants will receive retatrutide SC.
干预措施: Retatrutide (Drug)
Retatrutide Dose 1
Experimental
Participants will receive retatrutide subcutaneously (SC).
干预措施: Retatrutide (Drug)
Placebo
Placebo Comparator
Participants will receive placebo.
干预措施: Placebo (Drug)
Retatrutide Extension Period
Experimental
Participants will receive retatrutide after the placebo-controlled 80 week treatment period for an additional 24 weeks.
干预措施: Retatrutide (Drug)
结局指标
主要结局
Percent Change From Baseline in Body Weight
时间窗: Baseline, Week 80
Change from Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score for GOA1 Subset
时间窗: Baseline, Week 80
Change from Baseline in Apnea-Hypopnea Index (AHI) Events Per Hour for GSA1 Subset
时间窗: Baseline, Week 80
Percent Change from Baseline in Body Weight to
时间窗: Baseline, Week 104
Percent Change from Baseline in Body Weight in Participants in Extension Subset
时间窗: Baseline, Week 104
次要结局
- Change from Baseline in HbA1c(Baseline, Week 80)
- Change from Baseline in Body Mass Index (BMI)(Baseline, Week 80)
- Change from Baseline in Average Pain Intensity Numeric Rating Scale (API-NRS) Score for GOA1 Subset(Baseline, Week 80)
- Percent Change from Baseline in AHI for GSA1 Subset(Baseline, Week 80)
- Percent Change form Baseline in Fasting Insulin(Baseline, Week 80)
- Change from Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score(Baseline, Week 80)
- Change from Baseline in Worst Pain Intensity Numeric Rating Scale (WPI-NRS) Score for GOA1 Subset(Baseline, Week 80)
- Change from Baseline in Waist Circumference(Baseline, Week 80)
- Change from Baseline in Systolic Blood Pressure (SBP)(Baseline, Week 80)
- Percentage of Participants with ≥50% AHI Reduction from Baseline for GSA1 Subset(Baseline to Week 80)
- Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC)(Baseline through Week 80)
- A Hierarchical Combination of Functional Outcomes of Sleep Questionnaire (FOSQ) 10 Score, FOSQ Vigilance Domain Score, and FOSQ Activity Level Domain Score for GSA1 Subset(Baseline to Week 80)
- Percentage of Participants with AHI <5 or with AHI 5-14 with Epworth Sleepiness Scale (ESS) ≤10 for GSA1 Subset(Week 80)
- Change from Baseline in the WOMAC Physical Function Subscale Score for GOA1 Subset(Baseline, Week 80)
- Percent Change from Baseline in Body Weight in Participants with Baseline BMI ≥ 35 kg/m2(Baseline, Week 80)
- Percentage of Participants who Achieve Body Weight Reduction of ≥ 5%(Baseline through Week 80)
- Percentage of Participants who Achieve Body Weight Reduction of ≥ 10%(Baseline through Week 80)
- Percentage of Participants who Achieve Body Weight Reduction of ≥ 15%(Baseline through Week 80)
- Percentage of Participants who Achieve Body Weight Reduction of ≥ 20%(Baseline through Week 80)
- Percentage of Participants who Achieve Body Weight Reduction of ≥ 25%(Baseline through Week 80)
- Percentage of Participants who Achieve Body Weight Reduction of ≥ 30%(Baseline through Week 80)
- Percentage of Participants who Achieve Body Weight Reduction of ≥ 35%(Baseline through Week 80)
- Percent Change from Baseline in Triglycerides(Baseline, Week 80)
- Percent Change from Baseline in Non-High-Density Lipoprotein (HDL)-Cholesterol(Baseline, Week 80)
- Percent Change from Baseline in High-Sensitivity C-Reactive Protein (hsCRP)(Baseline, Week 80)
- Change from Baseline in Impact of Weight on Quality of Life-Lite Clinical Trial (IWQOL-Lite-CT) Physical Function Composite Score(Baseline, Week 80)
- Change from Baseline in IWQOL-Lite-CT Psychosocial Composite Score(Baseline, Week 80)
- Percentage of Participants who Achieve Waist-to-Height Ratio (WHtR) <0.5(Baseline through Week 80)
- Change from Baseline in Estimated Glomerular Filtration Rate (eGFR)(Baseline, Week 80)
- Percentage of Participants with a Change in Medication Use(Baseline through Week 80)
- Percentage of Participants who Develop Type 2 Diabetes(Baseline through Week 80)
- Time to Onset of Type 2 Diabetes(Baseline through Week 80)
- Percent Change from Baseline in Sleep Apnea-Specific Hypoxic Burden for GSA1 Subset(Baseline, Week 80)
- Change from Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form Sleep-related Impairment 8a T-score for GSA1 Subset(Baseline, Week 80)
- Change from Baseline in AHI Events Per Hour for GSA1 Subset in Participants with Baseline Body Mass Index (BMI) ≥ 35 kg/m2(Baseline, Week 80)
- Percentage of Participants who Achieve AHI < 5 for GSA1 Subset(Baseline, Week 80)
- Change from Baseline in ESS Score for GSA1 Subset(Baseline, Week 80)
- Change from Baseline in Functional Outcomes of Sleep Questionnaire (FOSQ) Total Score(Baseline to Week 80)
- Change from Baseline in PROMIS Sleep Disturbance Short Form 8b T-Score for GSA1 Subset(Baseline, Week 80)
- Change from Baseline in Neck Circumference for GSA1 Subset(Baseline, Week 80)
- Percentage of Participants who Achieve ≥ 50% Reduction in the WOMAC Pain Subscale for GOA1 Subset(Baseline through Week 80)
- Percentage of Participants who Achieve ≥ 50% Reduction in the WOMAC Physical Function Subscale for GOA1 Subset(Baseline through Week 80)
- Change from Baseline in the WOMAC Pain Subscale Score for GOA1 Subset with Baseline BMI ≥ 35 kg/m2(Baseline, Week 80)
- Change from Baseline in the WOMAC Stiffness Subscale Score for GOA1 Subset(Baseline, Week 80)
- Change from Baseline in the WOMAC Total Score for GOA1 Subset(Baseline, Week 80)
- Percentage of Participants with an Improved Categorical Shift in Patient Global Impression of Severity (PGIS) - Target Knee Function for GOA1 Subset(Baseline through Week 80)
- Percentage of Participants with an Improved Categorical Shift in PGIS - Target Knee Pain for GOA1 Subset(Baseline through Week 80)
- Change from Baseline in EQ-5D-5L for GOA1 Subset(Baseline, Week 80)
- Percentage of Participants with a Change in Use of Allowed Concomitant Pain Medication for GOA1 Subset(Baseline through Week 80)
- Change from Baseline in Joint Space Width for GOA1 Subset(Baseline, Week 80)
研究者
研究点 (266)
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