A Study of LY3502970 in Participants With Obesity or Overweight With Weight-related Comorbidities

Study Overview
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Brief Summary
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The main purpose of the study was to assess the effect of LY3502970 in participants who have obesity or are overweight.

Official Title
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A Phase 2 Study of Once-Daily LY3502970 Compared With Placebo in Participants Who Have Obesity or Are Overweight With Weight-Related Comorbidities

Conditions
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Obesity, Overweight and Obesity

Intervention / Treatment
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* Drug: LY3502970
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a body mass index (BMI) of ≥30-kilogram square meter (kg/m²) Have a BMI ≥27 kg/m² and <30 kg/m² with at least 1 of the following weight-related comorbidities eg; [Have hypertension, or dyslipidemia, cardiovascular disease] Have had a stable body weight for the 3 months prior to randomization (not more than 5% body weight gain and/or loss) Exclusion Criteria: Have any prior diagnosis of diabetes Have a prior or planned surgical treatment for obesity Have obesity induced by other endocrinological disorders or diagnosed monogenetic or syndromic forms of obesity Have renal impairment measured as estimated glomerular filtration rate (eGFR) <30 milliliter (mL)/minute (min)/1.73 m² Have a history of acute chronic pancreatitis Have a history of significant active or unstable Major Depressive Disorder (MDD) or other severe psychiatric disorder (for example, schizophrenia, bipolar disorder, or other serious mood or anxiety disorder) within the last 2 years Note: Participants with MDD or generalized anxiety disorder whose disease state is considered stable for the past 2 years and expected to remain stable throughout the course of the study, may be considered for inclusion if they are not on excluded medications. Within 3 months prior to screening: Have poorly controlled hypertension Have history of acute myocardial infarction Have history of cerebrovascular accident (stroke) Had hospitalization due to congestive heart failure (CHF) Have cancer Have human immunodeficiency virus (HIV) and/or positive HIV antibodies historically or at screening Have hepatitis B and/or positive hepatitis B surface antigen

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 12 milligram (mg) LY3502970<br>Participants received maintenance dose 12 mg with dose escalation starting from 3 mg,6 mg and then 12 mg LY3502970 administered orally once daily until 36 weeks. | Drug: LY3502970<br>* Administered orally<br>|
| Experimental: 24 mg LY3502970<br>Participants received maintenance dose 24 mg with dose escalation starting from 3 mg, 6 mg, 8 mg,12 mg and then 24 mg LY3502970 administered orally once daily until 36 weeks. | Drug: LY3502970<br>* Administered orally<br>|
| Experimental: 36 mg-1 LY3502970<br>Participants received maintenance dose 36 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 8 mg, 12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks. | Drug: LY3502970<br>* Administered orally<br>|
| Experimental: 36 mg-2 LY3502970<br>Participants received maintenance dose 36 mg with dose escalation starting from 3 mg, 6 mg,12 mg, 24 mg and then 36 mg LY3502970 administered orally once daily until 36 weeks. | Drug: LY3502970<br>* Administered orally<br>|
| Experimental: 45 mg-1 LY3502970<br>Participants received maintenance dose 45 mg with dose escalation starting from 3 mg, 6 mg, 8 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks. | Drug: LY3502970<br>* Administered orally<br>|
| Experimental: 45 mg-2 LY3502970<br>Participants received maintenance dose 45 mg with dose escalation starting from 2 mg, 3 mg, 6 mg, 12 mg, 24 mg, 36 mg and then 45 mg LY3502970 administered orally once daily until 36 weeks. | Drug: LY3502970<br>* Administered orally<br>|
| Placebo Comparator: Placebo<br>Participants received placebo administered orally once daily until 36 weeks. | Drug: Placebo<br>* Administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Body Weight in LY3502970 and Placebo | Least Squares (LS) mean was determined by mixed model repeated measures (MMRM) model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. | Baseline, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Body Weight in LY3502970 and Placebo | LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. | Baseline, Week 36 | 
| Change From Baseline in Body Weight in LY3502970 and Placebo | LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. | Baseline, Week 26 | 
| Change From Baseline in Body Weight in LY3502970 and Placebo | LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. | Baseline, Week 36 | 
| Change From Baseline in Waist Circumference in LY3502970 and Placebo | LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. | Baseline, Week 26 | 
| Change From Baseline in Waist Circumference in LY3502970 and Placebo | LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. | Baseline, Week 36 | 
| Change From Baseline in BMI in LY3502970 and Placebo | LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. | Baseline, Week 26 | 
| Change From Baseline in BMI in LY3502970 and Placebo | LS mean was determined by MMRM model with Baseline + Baseline BMI Group + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables. Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Percent Change from Baseline) = Unstructured. | Baseline, Week 36 | 
| Percentage of Participants With >=5% Body Weight Loss | Percentage of participants with >=5% body weight loss was reported. | Week 26 | 
| Percentage of Participants With >=10% Body Weight Loss | Percentage of participants with >=10% body weight loss was reported. | Week 26 | 
| Percentage of Participants With >=5% Body Weight Loss | Percentage of participants with >=5% body weight loss was reported. | Week 36 | 
| Percentage of Participants With >=10% Body Weight Loss | Percentage of participants with >=10% body weight loss was reported. | Week 36 |