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Completed

NCT Number: NCT06124807

A Study of LY3305677 Compared With Placebo 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.

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Key information

Conditions

Obesity Body Weight Body Weight Changes Nutrition Disorders Nutritional and Metabolic Diseases Overnutrition Overweight Overweight and Obesity Pathological Conditions, Signs and Symptoms Signs and Symptoms Weight Loss

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

The Institute for Liver Health II dba Arizona Clinical Trials - Mesa, Chandler, Arizona, United States

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Mazdutide

Drug

Administered subcutaneous (SC)

Other names: LY3305677

Placebo

Drug

Administered SC

Primary outcomes

  1. Percent Change From Baseline in Body Weight at Week 32

    Time frame: Baseline, 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).

Secondary outcomes

  1. Percent Change From Baseline in Body Weight at Week 48

    Time frame: Baseline, 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).

  2. Change From Baseline in Body Weight

    Time frame: Baseline, Week 32, 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 (Change from Baseline) = Unstructured. Strata is defined by joint levels of Sex and Baseline BMI (<=30, >30 kg/m^2).

  3. Mean Percentage of Participants Who Achieve ≥5% Body Weight Reduction

    Time frame: Baseline, Week 32, Week 48

    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.

  4. Mean Percentage of Participants Who Achieve ≥10% Body Weight Reduction

    Time frame: Baseline, Week 32, Week 48

    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.

  5. Change From Baseline in Body Mass Index (BMI)

    Time frame: Baseline, Week 32, 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 (Change from Baseline) = Unstructured. Strata is defined by joint levels of Sex and Baseline BMI (<=30, >30 kg/m^2).

  6. Number of Participants With Treatment Emergent Anti-drug Antibodies (TE-ADAs)

    Time frame: Baseline up to week 56

    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.

  7. Pharmacokinetics (PK): Area Under the Curve (AUC) of Mazdutide at Steady State

    Time frame: 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 samples were analyzed using a population PK approach to estimate AUC at steady state. Data presented are Geometric mean with 90% prediction interval.

  8. PK: Maximum Concentration (Cmax) of Mazdutide at Steady State

    Time frame: 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 samples were analyzed using a population PK approach to estimate Cmax at steady state. Data presented are Geometric mean with 90% prediction interval.

  9. Change From Baseline in Liver Fat Content (LFC) by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) in Participants With Baseline LFC >=5%

    Time frame: Baseline, Week 32, Week 48

    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).

  10. Percent Change From Baseline in Liver Fat Content by MRI-PDFF in Participants With Baseline LFC >=5%

    Time frame: Baseline, Week 32, Week 48

    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).

  11. Change From Baseline in Liver Fat Content by MRI-PDFF in Participants With Baseline LFC >=10%

    Time frame: Baseline, Week 32, Week 48

    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).

  12. Percent Change From Baseline in Liver Fat Content by MRI-PDFF in Participants With Baseline LFC >=10%

    Time frame: Baseline, Week 32, Week 48

    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).

  13. Mean Percentage of Participants With Baseline Liver Fat Content (LFC) >= 5% Who Achieved >30% Relative Reduction in LFC

    Time frame: Baseline, Week 32, Week 48

    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.

  14. Mean Percentage of Participants With Baseline Liver Fat Content (LFC) >=10% Who Achieved >30% Relative Reduction in LFC

    Time frame: Baseline, Week 32, Week 48

    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.

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

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

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Nov 9, 2023
Registry last updated
Apr 21, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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