A Study of LY3305677 Compared With Placebo in Adult Participants With Obesity or Overweight

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Overweight and Obesity
• Intervention / Treatment: Drug: Placebo; Drug: Mazdutide

• Study Type: Interventional
• Enrollment (Actual): 179
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Chandler, Arizona, United States, 85225
      • The Institute for Liver Health II dba Arizona Clinical Trials - Mesa
    • Scottsdale, Arizona, United States, 85260
      • Headlands Research - Scottsdale
    • Tucson, Arizona, United States, 85712
      • The Institute for Liver Health II dba Arizona Liver Health-Tucson
  • California
    • Huntington Park, California, United States, 90255
      • Velocity Clinical Research, Huntington Park
    • Rolling Hills Estates, California, United States, 90274
      • Peninsula Research Associates
    • Walnut Creek, California, United States, 94598
      • Diablo Clinical Research, Inc.
  • Florida
    • Fleming Island, Florida, United States, 32003
      • Northeast Research Institute (NERI)
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research, Inc.
    • Orlando, Florida, United States, 32803
      • Charter Research - Winter Park
    • The Villages, Florida, United States, 32162
      • Charter Research - Lady Lake
  • Hawaii
    • Honolulu, Hawaii, United States, 96817
      • Pacific Diabetes & Endocrine Center
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials - Andersonville
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials - Ravenswood
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Diabetes & Endocrinology
  • Kentucky
    • Louisville, Kentucky, United States, 40213
      • L-MARC Research Center
  • Massachusetts
    • Needham, Massachusetts, United States, 02492
      • Knownwell
  • Missouri
    • City of Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Las Vegas Medical Research
  • New York
    • Amherst, New York, United States, 14226
      • Dent Neurologic Institute
    • Port Jefferson Station, New York, United States, 11776
      • North Suffolk Neurology
  • North Carolina
    • New Bern, North Carolina, United States, 28562
      • Lucas Research, Inc.
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • CTI Clinical Research Center
  • Tennessee
    • Nashville, Tennessee, United States, 37211
      • Quality Medical Research
  • Texas
    • Austin, Texas, United States, 78745
      • IMA Clinical Research Austin
    • Dallas, Texas, United States, 75230
      • Velocity Clinical Research, Dallas
    • Houston, Texas, United States, 77079
      • PlanIt Research, PLLC
    • San Antonio, Texas, United States, 78229
      • Tekton Research - Fredericksburg Road
  • Virginia
    • Danville, Virginia, United States, 24541
      • Spectrum Medical, Inc.
  • Washington
    • Wenatchee, Washington, United States, 98801
      • Central Washington Health Services Association d/b/a Confluence Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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)

Exclusion Criteria:

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.

CWMM:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Mazdutide; Administered subcutaneous (SC); Other Names: LY3305677
Experimental: 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.	Drug: Mazdutide; Administered subcutaneous (SC); Other Names: LY3305677
Experimental: 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.	Drug: Mazdutide; Administered subcutaneous (SC); Other Names: LY3305677
Placebo Comparator: Placebo; Participants received Mazdutide matched placebo subcutaneously once weekly from Weeks 0 to 48.	Drug: Placebo; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Body Weight at 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).	Baseline, Week 32

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Body Weight at Week 48	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).	Baseline, Week 48
Change From Baseline in Body Weight	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 (Change from Baseline) = Unstructured. Strata is defined by joint levels of Sex and Baseline BMI (<=30, >30 kg/m^2).	Baseline, Week 32, Week 48
Mean Percentage of Participants Who Achieve ≥5% Body Weight Reduction	Mean percentage of participants who achieve ≥5% body weight reduction was calculated using imputed data with the logistic regression model Variable = Baseline + Treatment + Strata (Sex), where Treatment and Strata (Sex) are factors. Mean percentage of participants was calculated by combining percentage of participants achieving target at week 32 and week 48 respectively in imputed data sets using Rubin's rule.	Baseline, Week 32, Week 48
Mean Percentage of Participants Who Achieve ≥10% Body Weight Reduction	Mean percentage of participants who achieve ≥10% body weight reduction was calculated using imputed data with the logistic regression model Variable = Baseline + Treatment + Strata (Sex), where Treatment and Strata (Sex) are factors. Mean percentage of participants was calculated by combining percentage of participants achieving target at week 32 and week 48 respectively in imputed data sets using Rubin's rule.	Baseline, Week 32, Week 48
Change From Baseline in Body Mass Index (BMI)	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 (Change from Baseline) = Unstructured. Strata is defined by joint levels of Sex and Baseline BMI (<=30, >30 kg/m^2).	Baseline, Week 32, Week 48
Number of Participants With Treatment Emergent Anti-drug Antibodies (TE-ADAs)	Blood samples were tested to determine if a participant reacted to Mazdutide by producing anti-Mazdutide antibodies. A participant is TE ADA evaluable if there is at least one non-missing test result for ADA for each of the baseline period and the postbaseline period. A TE ADA evaluable participant is considered to be TE ADA+ if the participant has at least one postbaseline titer that is a 4-fold or greater increase in titer from baseline measurement. If baseline result is ADA Not Present, then the subject is TE ADA+ if there is at least one postbaseline result of ADA Present with titer >=1:20.	Baseline up to week 56
Pharmacokinetics (PK): Area Under the Curve (AUC) of Mazdutide at Steady State	PK samples were analyzed using a population PK approach to estimate AUC at steady state. Data presented are Geometric mean with 90% prediction interval.	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	PK samples were analyzed using a population PK approach to estimate Cmax at steady state. Data presented are Geometric mean with 90% prediction interval.	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%	Least squares means were calculated using an MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = Treatment*Time + log(Baseline)*Time + Strata*Time, where Treatment and Strata are factors. Variance-Covariance structure (Change from Baseline) = Unstructured. Strata is defined by joint levels of Sex and Baseline BMI (<=30, >30 kg/m^2).	Baseline, Week 32, Week 48
Percent Change From Baseline in Liver Fat Content by MRI-PDFF in Participants With Baseline LFC >=5%	Least squares means were calculated using an MMRM model for post-baseline measures: log (Actual Measurement/Baseline) = Treatment*Time + log (Baseline)*Time + Strata*Time, where Treatment and Strata are factors. Variance-Covariance structure (Change from Baseline) = Unstructured. Strata is defined by joint levels of Sex and Baseline BMI (<=30, >30 kg/m^2).	Baseline, Week 32, Week 48
Change From Baseline in Liver Fat Content by MRI-PDFF in Participants With Baseline LFC >=10%	Least squares means were calculated using an MMRM model for post-baseline measures: log (Actual Measurement/Baseline) = Treatment*Time + log (Baseline)*Time + Strata*Time, where Treatment and Strata are factors. Variance-Covariance structure (Change from Baseline) = Unstructured. Strata is defined by joint levels of Sex and Baseline BMI (<=30, >30 kg/m^2).	Baseline, Week 32, Week 48
Percent Change From Baseline in Liver Fat Content by MRI-PDFF in Participants With Baseline LFC >=10%	Least squares means were calculated using an MMRM model for post-baseline measures: log (Actual Measurement/Baseline) = Treatment*Time + log (Baseline)*Time + Strata*Time, where Treatment and Strata are factors. Variance-Covariance structure (Change from Baseline) = Unstructured. Strata is defined by joint levels of Sex and Baseline BMI (<=30, >30 kg/m^2).	Baseline, Week 32, Week 48
Mean Percentage of Participants With Baseline Liver Fat Content (LFC) >= 5% Who Achieved >30% Relative Reduction in LFC	mean Percentage of participants with baseline liver fat content (LFC) >= 5% who achieved >30% relative reduction in LFC was estimated using imputed data with the logistic regression model Variable = Baseline + Treatment + Strata (Sex), where Treatment and Strata (Sex) are factors. Mean percentage of participants was calculated by combining percentage of participants achieving target at week 32 and week 48 respectively in imputed data sets using Rubin's rule.	Baseline, Week 32, Week 48
Mean Percentage of Participants With Baseline Liver Fat Content (LFC) >=10% Who Achieved >30% Relative Reduction in LFC	Mean Percentage of participants with baseline liver fat content (LFC) >=10% who achieved >30% relative reduction in LFC was estimated using imputed data with the logistic regression model Variable = Baseline + Treatment + Strata (Sex), where Treatment and Strata (Sex) are factors. Mean percentage of participants was calculated by combining percentage of participants achieving target at week 32 and week 48 respectively in imputed data sets using Rubin's rule.	Baseline, Week 32, Week 48

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

• A Study of LY3305677 Compared With Placebo in Adult Participants With Obesity or Overweight

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2023
• Primary Completion (Actual): January 22, 2025
• Study Completion (Actual): July 9, 2025

Study Registration Dates

• First Submitted: November 6, 2023
• First Submitted That Met QC Criteria: November 6, 2023
• First Posted (Actual): November 9, 2023

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: March 31, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Weight Loss; Incretins; Overnutrition
• Additional Relevant MeSH Terms: Nutrition Disorders; Body Weight; Body Weight Changes; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Weight Loss; Overnutrition; mazdutide
• Other Study ID Numbers: 18661; W8M-MC-OXA1 (Other Identifier: Eli Lilly and Company); CWMM Master Protocol (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Plan Description:

Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No