NCT05929066 - A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight | Crick

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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.

Outcomes

Primary Outcomes

Percent Change From Baseline in Body Weight

Time frame: Baseline, Week 80

Change from Baseline in Apnea-Hypopnea Index (AHI) Events Per Hour for GSA1 Subset

Time frame: Baseline, Week 80

Change from Baseline in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Subscale Score for GOA1 Subset

Time frame: Baseline, Week 80

Percent Change from Baseline in Body Weight in Participants in Extension Subset

Time frame: Baseline, Week 104

Secondary Outcomes

Percent Change from Baseline in Body Weight in Participants with Baseline BMI ≥ 35 kg/m2

Time frame: Baseline, Week 80

Percentage of Participants who Achieve Body Weight Reduction of ≥ 5%

Time frame: Baseline through Week 80

Percentage of Participants who Achieve Body Weight Reduction of ≥ 10%

Time frame: Baseline through Week 80

Percentage of Participants who Achieve Body Weight Reduction of ≥ 15%

Time frame: Baseline through Week 80

Percentage of Participants who Achieve Body Weight Reduction of ≥ 20%

Time frame: Baseline through Week 80

Percentage of Participants who Achieve Body Weight Reduction of ≥ 25%

Time frame: Baseline through Week 80

Percentage of Participants who Achieve Body Weight Reduction of ≥ 30%

Time frame: Baseline through Week 80

Percentage of Participants who Achieve Body Weight Reduction of ≥ 35%

Time frame: Baseline through Week 80

Change from Baseline in Waist Circumference

Time frame: Baseline, Week 80

Change from Baseline in Systolic Blood Pressure (SBP)

Time frame: Baseline, Week 80

Percent Change from Baseline in Triglycerides

Time frame: Baseline, Week 80

Percent Change from Baseline in Non-High-Density Lipoprotein (HDL)-Cholesterol

Time frame: Baseline, Week 80

Percent Change form Baseline in Fasting Insulin

Time frame: Baseline, Week 80

Percent Change from Baseline in High-Sensitivity C-Reactive Protein (hsCRP)

Time frame: Baseline, Week 80

Change from Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score

Time frame: Baseline, Week 80

Change from Baseline in Impact of Weight on Quality of Life-Lite Clinical Trial (IWQOL-Lite-CT) Physical Function Composite Score

Time frame: Baseline, Week 80

Change from Baseline in IWQOL-Lite-CT Psychosocial Composite Score

Time frame: Baseline, Week 80

Change from Baseline in Body Mass Index (BMI)

Time frame: Baseline, Week 80

Percentage of Participants who Achieve Waist-to-Height Ratio (WHtR) <0.5

Time frame: Baseline through Week 80

Change from Baseline in HbA1c

Time frame: Baseline, Week 80

Change from Baseline in Estimated Glomerular Filtration Rate (eGFR)

Time frame: Baseline, Week 80

Percentage of Participants with a Change in Medication Use

Time frame: Baseline through Week 80

Percentage of Participants who Develop Type 2 Diabetes

Time frame: Baseline through Week 80

Time to Onset of Type 2 Diabetes

Time frame: Baseline through Week 80

Percent Change from Baseline in AHI for GSA1 Subset

Time frame: Baseline, Week 80

Percentage of Participants with ≥50% AHI Reduction from Baseline for GSA1 Subset

Time frame: Baseline to Week 80

Percentage of Participants with AHI <5 or with AHI 5-14 with Epworth Sleepiness Scale (ESS) ≤10 for GSA1 Subset

Time frame: Week 80

Percent Change from Baseline in Sleep Apnea-Specific Hypoxic Burden for GSA1 Subset

Time frame: 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

Time frame: 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

Time frame: Baseline, Week 80

Percentage of Participants who Achieve AHI < 5 for GSA1 Subset

Time frame: Baseline, Week 80

Change from Baseline in ESS Score for GSA1 Subset

Time frame: Baseline, Week 80

Change from Baseline in Functional Outcomes of Sleep Questionnaire (FOSQ) Total Score

Time frame: Baseline to Week 80

Change from Baseline in PROMIS Sleep Disturbance Short Form 8b T-Score for GSA1 Subset

Time frame: Baseline, Week 80

Change from Baseline in Neck Circumference for GSA1 Subset

Time frame: Baseline, Week 80

Change from Baseline in the WOMAC Physical Function Subscale Score for GOA1 Subset

Time frame: Baseline, Week 80

Percentage of Participants who Achieve ≥ 50% Reduction in the WOMAC Pain Subscale for GOA1 Subset

Time frame: Baseline through Week 80

Percentage of Participants who Achieve ≥ 50% Reduction in the WOMAC Physical Function Subscale for GOA1 Subset

Time frame: Baseline through Week 80

Change from Baseline in the WOMAC Pain Subscale Score for GOA1 Subset with Baseline BMI ≥ 35 kg/m2

Time frame: Baseline, Week 80

Change from Baseline in the WOMAC Stiffness Subscale Score for GOA1 Subset

Time frame: Baseline, Week 80

Change from Baseline in the WOMAC Total Score for GOA1 Subset

Time frame: Baseline, Week 80

Change from Baseline in Average Pain Intensity Numeric Rating Scale (API-NRS) Score for GOA1 Subset

Time frame: Baseline, Week 80

Change from Baseline in Worst Pain Intensity Numeric Rating Scale (WPI-NRS) Score for GOA1 Subset

Time frame: Baseline, Week 80

Percentage of Participants with an Improved Categorical Shift in Patient Global Impression of Severity (PGIS) - Target Knee Function for GOA1 Subset

Time frame: Baseline through Week 80

Percentage of Participants with an Improved Categorical Shift in PGIS - Target Knee Pain for GOA1 Subset

Time frame: Baseline through Week 80

Change from Baseline in EQ-5D-5L for GOA1 Subset

Time frame: Baseline, Week 80

Percentage of Participants with a Change in Use of Allowed Concomitant Pain Medication for GOA1 Subset

Time frame: Baseline through Week 80

Change from Baseline in Joint Space Width for GOA1 Subset

Time frame: Baseline, Week 80

Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC)

AUC is presented as a single average measure of AUC across the study duration.

Time frame: Baseline through Week 80

A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight

Overview

Conditions

Interventions

Eligibility

Locations (134)

Outcomes

Primary Outcomes

Secondary Outcomes