NCT03596177CompletedPhase 2
An Exploratory Phase 2a, Randomised, Double-blind, Placebo-controlled Study to Evaluate the Effect of MEDI0382 on Energy Balance in Overweight and Obese Subjects With Type 2 Diabetes Mellitus
Conditions
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- MedImmune LLC
- Enrollment
- 28
- Locations
- 1
- Primary Endpoint
- Percent Change in Body Weight From Baseline to Day 59
Study Overview
Brief Summary
An exploratory study to evaluate the effect of MEDI0382 on energy balance in overweight and obese participants with type 2 diabetes mellitus
Detailed Description
An exploratory Phase 2a, randomised, double-blind, placebo-controlled study to evaluate the effect of MEDI0382 on energy balance in overweight and obese participants with type 2 diabetes mellitus
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 30 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participants aged >= 30 and <= 75 years at screening
- •Provision of signed and dated written informed consent (except for consent for genetic and non-genetic research and additional optional assessments) prior to any protocol-related procedures
- •Body Mass Index > 28 and <= 40 kg/m^2 at screening
- •Glycated haemoglobin (HbA1c) <= 8.0% at screening
- •Diagnosed with type 2 diabetes (T2DM) with glucose control managed with metformin, with or without a dipeptidyl peptidase 4 (DPPIV) inhibitor, Sodium-glucose co-transporter-2 inhibitors (SGLT2i), sulfonylurea, or meglitinide, where no significant dose change (increase or decrease > 50%) has occurred in the 3 months prior to screening; if the participant is on dual therapy, a 4-week washout of the non-metformin therapy (DPPIV inhibitor, SGLT2i, sulfonylurea, or meglitinide) will be required prior to Visit
- •Female participants of childbearing potential must have a negative pregnancy test at screening and randomisation, and must not be lactating.
- •Female participants of childbearing potential who are sexually active with a non-sterilised male partner must be using at least one highly effective method of contraception from screening and must agree to continue using such precautions up until 4 weeks after the last dose of study drug
Exclusion Criteria
- •History of, or any existing condition(s) that, in the opinion of the investigator, would interfere with evaluation of the study drug, put the participant at risk, influence the participant's ability to participate or affect the interpretation of the results of the study and/or any participant unable or unwilling to follow study procedures
- •Any participant with a cardiac pacemaker or implanted/portable electronic device
- •Any participant who has received another study drug as part of a clinical study or a Glucagon-like peptide-1 (GLP-1) analogue-containing preparation within the last 30 days or 5 half-lives of the drug (whichever is longer) at the time of screening (Visit 1)
- •Any participant who has received any of the following medications within the specified timeframe prior to Visit 2: herbal preparations or drugs licensed for control of body weight or appetite (eg, orlistat, bupropion, naltrexone, phentermine-topiramate, phentermine, lorcaserin, opiates, domperidone, metoclopramide, or other drugs known to alter gastric emptying)
- •Concurrent participation in another study with a study drug and prior randomisation in this study is prohibited
- •Severe allergy/hypersensitivity to any of the proposed study treatments, excipients, or standardised meals
- •Symptoms of acutely decompensated blood glucose control (eg, thirst, polyuria, weight loss), a history of type 1 diabetes mellitus or diabetic ketoacidosis, or if the participant has been treated with daily SC insulin within 90 days prior to screening.
- •Abnormal thyroid stimulating hormone (TSH) level of < 0.03 Milli-International Units Per Litre (mIU/L) or > 10 mIU/L confirmed on two consecutive tests
- •Regularly engage in high intensity exercise at least three times per week or have done so in the prior three months
- •Clinically significant inflammatory bowel disease, gastroparesis or other severe disease or surgery affecting the upper gastrointestinal tract (including weight-reducing surgery and procedures) which may affect gastric emptying or could affect the interpretation of safety and tolerability data
- •Acute or chronic pancreatitis
- •Significant hepatic disease (except for nonalcoholic steatohepatitis or nonalcoholic fatty liver disease without portal hypertension or cirrhosis) and/or participants with any of the following results at screening:
- •Aspartate transaminase (AST) >= 3 × upper limit of normal (ULN)
- •Alanine transaminase (ALT) >= 3 × ULN
- •Total bilirubin >= 2 × ULN
- •Impaired renal function defined as estimated glomerular filtration rate (eGFR) < 45 mL/minute/1.73 m^2 at screening (GFR estimated according to the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) or the Modification of Diet in Renal Disease (MDRD) using MDRD Study Equation isotope dilution mass spectrometry-traceable [International System of Units (SI) units]
- •Poorly controlled hypertension defined as:
- •Systolic blood pressure (BP) > 180 mm Hg
- •Diastolic BP or > 100 mm Hg After 10 minutes of supine rest and confirmed by repeated measurement at screening.
- •Participants who fail BP screening criteria may be considered for 24-hour ambulatory BP monitoring at the discretion of the investigator. Participants who maintain a mean 24-hour BP <= 180/100 mmHg with a preserved nocturnal dip of > 15% will be considered eligible
- •Unstable angina pectoris, myocardial infarction, transient ischemic attack or stroke within 3 months prior to screening, or participants who have undergone percutaneous coronary intervention or a coronary artery bypass graft within the past 6 months or who are due to undergo these procedures at the time of screening
- •Severe congestive heart failure (New York Heart Association Class III or IV)
- •Basal calcitonin level > 50 ng/L at screening or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia
- •History of neoplastic disease within 5 years prior to screening, except for adequately treated basal cell, squamous cell skin cancer, or in situ cervical cancer
- •Any positive results for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) antibody
- •Substance dependence or history of alcohol abuse and/or excess alcohol intake
- •Involvement of any AstraZeneca, Medimmune Ltd, contract research organization (CRO), or National Institute for Health Research/Wellcome Trust Cambridge Clinical Research Facility employee or their close relatives
Arms & Interventions
MEDI0382
Experimental
Participants will receive subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Intervention: MEDI0382 (Drug)
MEDI0382
Experimental
Participants will receive subcutaneous (SC) injection of placebo for 16 days in the single-blind treatment period, and then SC injection of MEDI0382 titrated up to 300 μg for 42 days (100 μg for 4 days, followed by 200 μg for 4 days, and finally 300 μg for 34 days) in double-blind treatment period.
Intervention: Placebo (Drug)
Placebo
Placebo Comparator
Participants will receive SC injection of placebo for 16 days in the single-blind treatment period, and then SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period.
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Percent Change in Body Weight From Baseline to Day 59
Time Frame: Baseline (Day 17) and Day 59
Percent change in body weight from baseline to Day 59 is reported. Day 17 was considered as baseline for this outcome measure. The last observation carried forward (LOCF) analysis was used for missing data imputation for Day 59.
Secondary Outcomes
- Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59(Baseline (Day 16) to Day 32 and Day 59)
- Percent Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59(Baseline (Day 16), Day 32, and Day 59)
- Percent Change in Total Energy Expenditure (TEE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58(Baseline (Day 15) and Day 58)
- Change in TEE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58(Baseline (Day 15) and Day 58)
- Percent Change in Activity Energy Expenditure (AEE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58(Baseline (Day 15) and Day 58)
- Change in AEE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58(Baseline (Day 15) and Day 58)
- Percent Change in Resting Energy Expenditure (REE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58(Baseline (Day 15) and Day 58)
- Change in REE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58(Baseline (Day 15) and Day 58)
- Percent Change in REE as Measured by Hood Indirect Calorimetry From Baseline to Day 32(Baseline (Day 16) and Day 32)
- Change in REE as Measured by Hood Indirect Calorimetry From Baseline to Day 32(Baseline (Day 16) and Day 32)
- Change in Body Weight From Baseline to Day 59(Baseline (Day 17) and Day 59)
- Percent Change in Total Body Fat Mass as Measured by Dual-energy X-ray Absorptiometry (DXA) From Baseline to Day 59(Baseline (Day -1) and Day 59)
- Change in Total Body Fat Mass as Measured by DXA From Baseline to Day 59(Baseline (Day -1) and Day 59)
- Percent Change in Total Body Fat Mass: Lean Mass Ratio as Measured by DXA From Baseline to Day 59(Baseline (Day -1) and Day 59)
- Change in Total Body Fat Mass: Lean Mass Ratio as Measured by DXA From Baseline to Day 59(Baseline (Day -1) and Day 59)
- Change in Fasting Glucose During a Mixed-meal Tolerance Test (MMTT) From Baseline to Day 59(Baseline (Day -1) and Day 59)
- Percent Change in Glucose Area Under the Concentration-time Curve at 0 to 4 Hours (AUC0-4hrs) During a MMTT From Baseline to Day 59(Baseline (Day -1) and Day 59)
- Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs(Day 17 through 28 days post last dose (approximately 14 months))
- Number of Participants With Abnormal Vital Signs Reported as TEAEs(Day 17 through 28 days post last dose (approximately 14 months))
- Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs(Day 17 through 28 days post last dose (approximately 14 months))
- Number of Participants With Positive Anti-drug Antibodies (ADAs) to MEDI0382(Day 17 (predose), Day 32 (predose), Day 59; and 28 days post last dose (approximately 14 months))
- Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)(Day 17 through 28 days post last dose (approximately 14 months))
Investigators
Study Sites (1)
Loading locations...
Similar Trials
Completed
Phase 2
A Study to Evaluate DD01 in Overweight/Obese Subjects With MASLD/MASHNAFLDNASHNCT06410924Neuraly, Inc.67
Completed
Phase 2
A Study to Investigate the Effect of MEDI0382 on Hepatic Glycogen Metabolism in Overweight and Obese Subjects With Type 2 Diabetes Mellitus.Type 2 Diabetes MellitusNCT03555994MedImmune LLC51
Completed
Phase 2
A Study of LY3502970 in Participants With Obesity or Overweight With Weight-related ComorbiditiesOverweight and ObesityObesityNCT05051579Eli Lilly and Company272
Completed
Phase 2
A Study of LY3437943 in Participants Who Have Obesity or Are OverweightOverweightObesityNCT04881760Eli Lilly and Company338
Completed
Phase 2
A Phase 2b Study to Examine the Safety and Efficacy of Once-Weekly MET097 in Adults With Obesity or OverweightObesityNCT06712836Pfizer239