Clinical trial NCT03596177: A Study to Evaluate the Effect of MEDI0382 on Energy Balance in Overweight and Obese Participants With Type 2 Diabetes Mellitus
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type II
Obesity
Keywords: Diabetes Mellitus, Type II
Obesity
MEDI0382
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2018-07-23
Enrollment: 28
Sex: ALL
Minimum age (years): 30
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised, Double-Blind, Placebo-Controlled
Primary purpose: TREATMENT

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

Eligibility criteria: Inclusion Criteria:

1. Participants aged \>= 30 and \<= 75 years at screening
2. 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
3. Body Mass Index \> 28 and \<= 40 kg/m\^2 at screening
4. Glycated haemoglobin (HbA1c) \<= 8.0% at screening
5. 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 4.
6. Female participants of childbearing potential must have a negative pregnancy test at screening and randomisation, and must not be lactating.
7. 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:

1. 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
2. Any participant with a cardiac pacemaker or implanted/portable electronic device
3. 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)
4. 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)
5. Concurrent participation in another study with a study drug and prior randomisation in this study is prohibited
6. Severe allergy/hypersensitivity to any of the proposed study treatments, excipients, or standardised meals
7. 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.
8. 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
9. Regularly engage in high intensity exercise at least three times per week or have done so in the prior three months
10. 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
11. Acute or chronic pancreatitis
12. 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:

    1. Aspartate transaminase (AST) \>= 3 × upper limit of normal (ULN)
    2. Alanine transaminase (ALT) \>= 3 × ULN
    3. Total bilirubin \>= 2 × ULN
13. 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 \[International System of Units (SI) units\]
14. Poorly controlled hypertension defined as:

    1. Systolic blood pressure (BP) \> 180 mm Hg
    2. 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
15. 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
16. Severe congestive heart failure (New York Heart Association Class III or IV)
17. Basal calcitonin level \> 50 ng/L at screening or history/family history of medullary thyroid carcinoma or multiple endocrine neoplasia
18. 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
19. Any positive results for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody and human immunodeficiency virus (HIV) antibody
20. Substance dependence or history of alcohol abuse and/or excess alcohol intake
21. 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

Primary outcomes:
measure: Percent Change in Body Weight From Baseline to Day 59
timeFrame: Baseline (Day 17) and Day 59
Secondary outcomes:
measure: Percent Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59
timeFrame: Baseline (Day 16), Day 32, and Day 59
measure: Change in Total Energy Intake From the ad Libitum Lunch From Baseline to Day 32 and Day 59
timeFrame: Baseline (Day 16) to Day 32 and Day 59
measure: Percent Change in Total Energy Expenditure (TEE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58
timeFrame: Baseline (Day 15) and Day 58
measure: Change in TEE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58
timeFrame: Baseline (Day 15) and Day 58
measure: Percent Change in Activity Energy Expenditure (AEE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58
timeFrame: Baseline (Day 15) and Day 58
measure: Change in AEE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58
timeFrame: Baseline (Day 15) and Day 58
measure: Percent Change in Resting Energy Expenditure (REE) as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58
timeFrame: Baseline (Day 15) and Day 58
measure: Change in REE as Measured by Whole Room Indirect Calorimetry From Baseline to Day 58
timeFrame: Baseline (Day 15) and Day 58
measure: Percent Change in REE as Measured by Hood Indirect Calorimetry From Baseline to Day 32
timeFrame: Baseline (Day 16) and Day 32
measure: Change in REE as Measured by Hood Indirect Calorimetry From Baseline to Day 32
timeFrame: Baseline (Day 16) and Day 32
measure: Change in Body Weight From Baseline to Day 59
timeFrame: Baseline (Day 17) and Day 59
measure: Percent Change in Total Body Fat Mass as Measured by Dual-energy X-ray Absorptiometry (DXA) From Baseline to Day 59
timeFrame: Baseline (Day -1) and Day 59
measure: Change in Total Body Fat Mass as Measured by DXA From Baseline to Day 59
timeFrame: Baseline (Day -1) and Day 59
measure: Percent Change in Total Body Fat Mass: Lean Mass Ratio as Measured by DXA From Baseline to Day 59
timeFrame: Baseline (Day -1) and Day 59
measure: Change in Total Body Fat Mass: Lean Mass Ratio as Measured by DXA From Baseline to Day 59
timeFrame: Baseline (Day -1) and Day 59
measure: Change in Fasting Glucose During a Mixed-meal Tolerance Test (MMTT) From Baseline to Day 59
timeFrame: Baseline (Day -1) and Day 59
measure: 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
timeFrame: Baseline (Day -1) and Day 59
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: Day 17 through 28 days post last dose (approximately 14 months)
measure: Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs
timeFrame: Day 17 through 28 days post last dose (approximately 14 months)
measure: Number of Participants With Abnormal Vital Signs Reported as TEAEs
timeFrame: Day 17 through 28 days post last dose (approximately 14 months)
measure: Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs
timeFrame: Day 17 through 28 days post last dose (approximately 14 months)
measure: Number of Participants With Positive Anti-drug Antibodies (ADAs) to MEDI0382
timeFrame: Day 17 (predose), Day 32 (predose), Day 59; and 28 days post last dose (approximately 14 months)
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Research Site
Study officials:
References: