Overweight or Obese, Type 2 Diabetes Mellitus (T2DM)
Conditions
Brief summary
This is a multi-center, randomized, double-blind, placebo-controlled, parallel group dose-finding study to evaluate the efficacy and safety of enicepatide at low, middle, and high doses in participants who are overweight or obese with Type 2 diabetes mellitus (T2DM).
Interventions
DRUGPlacebo
Placebo will be volume-matched and administered subcutaneously (SC) once weekly.
DRUGEnicepatide
Enicepatide will be administered subcutaneously (SC) once weekly at the randomized dosing regimen.
Sponsors
Carmot Therapeutics, Inc.
Hoffmann-La Roche
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
* Male or female, 18 to 75 years of age * Body mass index (BMI) ≥25.0 kg/m\^2 * Have a diagnosis of Type 2 Diabetes Mellitus (T2DM) according to the World Health Organization classification or other locally applicable standards * Have an HbA1c ≥7% and ≤10.5% * Management of T2DM with diet and exercise alone, metformin, or a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, as monotherapy or in combination, per approved local label * At least one self-reported unsuccessful diet/exercise effort to lose body weight
Exclusion criteria
* Have Type 1 Diabetes Mellitus (T1DM), history of ketosis or hyperosmolar state/coma, or any other types of diabetes except T2DM * Have had 1 or more episodes of Level 3 hypoglycemia or have had hypoglycemia unawareness within 3 months prior to screening * Have history or presence of proliferative diabetic retinopathy, diabetic macular edema, or non-proliferative diabetic retinopathy that requires acute treatment * Have evidence of clinically significant autonomic neuropathy (symptoms may include resting tachycardia, orthostatic hypotension, or diabetic diarrhea) * Had treatment with any oral antihyperglycemic medications, with the exception of metformin or SGLT-2 inhibitors, within 3 months prior to screening or planned concurrent treatment with these medications during the study * Had treatment with injectable antihyperglycemic medication, with the exception of short-term insulin, within 6 months prior to screening or planned concurrent treatment with these medications during the study * Self-reported body weight change of \>5 kg within 3 months before screening * Any unbalanced/extreme diets, such as very low calorie, low carbohydrate, very high protein, ketogenic, or intermittent diets, within 3 months of the screening visit, or plan to be on such diets during the study * Current or recent use of any treatment that promotes weight loss or glucose metabolism * Current or recent use of treatment that may cause weight gain * Prior or planned surgical treatment or procedure for obesity, except for liposuction or abdominoplasty if performed \>1 year prior to screening. Participants with a history of devices, such as LAP-BAND® or intragastric balloon, are permitted, if devices were removed \>1 year prior to screening. * History of clinically significant or active gastric emptying abnormality (e.g., severe gastroparesis or gastric outlet obstruction, intestinal obstruction), or chronic use of medications that directly affect GI motility * History of chronic pancreatitis or acute pancreatitis or have signs and symptoms of acute pancreatitis at screening * Have obesity induced by other endocrinologic disorders (e.g., Cushing syndrome) or diagnosed monogenetic or syndromic forms of obesity * History or diagnosis of significant active or unstable major depressive disorder or any history/diagnosis of other severe psychiatric conditions (e.g., schizophrenia; bipolar disorder; other serious mood disorder or anxiety disorder, or hyperactivity disorder) within the last year before screening * History of any hematologic conditions that may interfere with HbA1c measurement (e.g., hemolytic anemias, sickle cell disease, other hemoglobinopathies) * Family or personal history of medullary thyroid carcinoma * Women who are pregnant, breastfeeding, or intend to become pregnant, or are of childbearing potential and not using a highly effective contraceptive method as required per protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change in Body Weight from Baseline to Week 36 | Baseline to Week 36 |
| Change in Glycated Hemoglobin (HbA1c) from Baseline to Week 36 | Baseline to Week 36 |
Secondary
| Measure | Time frame |
|---|---|
| Percent Change in Body Weight from Baseline to Week 48 | Baseline to Week 48 |
| Change in HbA1c from Baseline to Week 48 | Baseline to Week 48 |
| Percentage of Participants with HbA1c <7.0% at Weeks 36 and 48 | Weeks 36 and 48 |
| Percentage of Participants with Body Weight Reduction ≥5%, ≥10%, ≥15%, ≥20%, and ≥25% from Baseline to Week 36 | Baseline and Week 36 |
| Percentage of Participants with Body Weight Reduction ≥5%, ≥10%, ≥15%, ≥20%, and ≥25% from Baseline to Week 48 | Baseline and Week 48 |
| Percent Change in Body Weight from Baseline to Week 28 | Baseline and Week 28 |
| Absolute Change in Body Weight (kg) from Baseline to Weeks 36 and 48 | Baseline to Weeks 36 and 48 |
| Percent Change in Body Weight from Baseline to Weeks 16, 28, 36, and 48 by Obesity Class | Baseline to Weeks 16, 28, 36, and 48 |
| Change in HbA1c from Baseline to Weeks 16 and 28 | Baseline to Weeks 16 and 28 |
| Change in HbA1c from Baseline to Weeks 16, 28, 36, and 48 by Obesity Class | Baseline to Weeks 16, 28, 36, and 48 |
| Percentage of Participants with HbA1c ≤6.5% at Weeks 16, 28, 36, and 48 | Weeks 16, 28, 36, and 48 |
| Percentage of Participants with HbA1c <5.7% at Weeks 16, 28, 36, and 48 | Weeks 16, 28, 36, and 48 |
| Change in 7-point Self-Monitored Blood Glucose (SMBG) Profile at Weeks 16, 28, 36, and 48 | Weeks 16, 28, 36, and 48 |
| Percentage of Participants who Achieve HbA1c ≤6.5% and ≥10.0% Weight Reduction at Weeks 16, 28, 36, and 48 | Baseline, Weeks 16, 28, 36, and 48 |
| Percentage of Participants who Achieve HbA1c <7.0% and ≥5.0% Weight Reduction at Weeks 16, 28, 36, and 48 | Baseline, Weeks 16, 28, 36, and 48 |
| Change in Body Mass Index (BMI) from Baseline to Weeks 36 and 48 | Baseline, Weeks 36 and 48 |
| Change in Waist Circumference from Baseline to Weeks 36 and 48 | Baseline, Weeks 36 and 48 |
| Change in Hip Circumference from Baseline to Weeks 36 and 48 | Baseline, Weeks 36 and 48 |
| Change in Waist-to-Hip Ratio from Baseline to Weeks 36 and 48 | Baseline, Weeks 36 and 48 |
| Change in Waist-to-Height Ratio from Baseline to Weeks 36 and 48 | Baseline, Weeks 36 and 48 |
| Change in Fasting Plasma Glucose from Baseline to Weeks 16, 28, 36, and 48 | Baseline to Weeks 16, 28, 36, and 48 |
| Change in Fasting Insulin from Baseline to Weeks 16, 28, 36, and 48 | Baseline to Weeks 16, 28, 36, and 48 |
| Change in Fasting C-peptide from Baseline to Weeks 16, 28, 36, and 48 | Baseline to Weeks 16, 28, 36, and 48 |
| Change in Fasting Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) from Baseline to Weeks 16, 28, 36, and 48 | Baseline to Weeks 16, 28, 36, and 48 |
Countries
Argentina, Canada, Mexico, New Zealand, Puerto Rico, United States
Contacts
STUDY_DIRECTORClinical Trials
Carmot Therapeutics, Inc., a Member of the Roche Group
Outcome results
None listed