Obesity, Overweight and Obesity
Conditions
Keywords
Incretins, Weight Loss, Overnutrition
Brief summary
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.
Interventions
DRUGMazdutide
Administered subcutaneous (SC)
DRUGPlacebo
Administered SC
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Body Weight at Week 32 | 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
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Body Weight at Week 48 | 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). |
| Change From Baseline in Body Weight | 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). |
| Mean Percentage of Participants Who Achieve ≥5% Body Weight Reduction | 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. |
| Mean Percentage of Participants Who Achieve ≥10% Body Weight Reduction | 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. |
| Change From Baseline in Body Mass Index (BMI) | 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). |
| Number of Participants With Treatment Emergent Anti-drug Antibodies (TE-ADAs) | 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. |
| Pharmacokinetics (PK): Area Under the Curve (AUC) of Mazdutide at Steady State | 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. |
| PK: Maximum Concentration (Cmax) of Mazdutide at Steady State | 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. |
| Change From Baseline in Liver Fat Content (LFC) by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) in Participants With Baseline LFC >=5% | 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). |
| Percent Change From Baseline in Liver Fat Content by MRI-PDFF in Participants With Baseline LFC >=5% | 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). |
| Change From Baseline in Liver Fat Content by MRI-PDFF in Participants With Baseline LFC >=10% | 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). |
| Percent Change From Baseline in Liver Fat Content by MRI-PDFF in Participants With Baseline LFC >=10% | 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). |
| Mean Percentage of Participants With Baseline Liver Fat Content (LFC) >= 5% Who Achieved >30% Relative Reduction in LFC | 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. |
| Mean Percentage of Participants With Baseline Liver Fat Content (LFC) >=10% Who Achieved >30% Relative Reduction in LFC | 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. |
Countries
United States
Contacts
STUDY_DIRECTORCall 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
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 47.7 years STANDARD_DEVIATION 12.3 |
| Body Weight | 103.1 Kilograms (Kg) STANDARD_DEVIATION 21.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 9 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 6 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 125 Participants |
| Region of Enrollment United States | 32 Participants |
| Sex: Female, Male Female | 118 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 32 | 0 / 47 | 0 / 51 |
| other Total, other adverse events | 34 / 47 | 29 / 32 | 37 / 47 | 45 / 51 |
| serious Total, serious adverse events | 1 / 47 | 1 / 32 | 1 / 47 | 2 / 51 |
Outcome results
None listed