A Study to Evaluate the Effect of MEDI0382 on Energy Balance in Overweight and Obese Participants With Type 2 Diabetes Mellitus

NCT ID: NCT03596177

Last Updated: 2023-01-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-09-26
• Study Completion Date: 2019-12-22

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

Conditions

Diabetes Mellitus, Type II; Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

MEDI0382

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.

Group Type: EXPERIMENTAL

MEDI0382

Intervention Type: DRUG

MEDI0382 will be administered subcutaneously, 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.

Placebo

Intervention Type: DRUG

Placebo will be administered subcutaneously for 16 days in the single-blind treatment period in both MEDI0382 and placebo arms, and SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period in placebo arm.

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo will be administered subcutaneously for 16 days in the single-blind treatment period in both MEDI0382 and placebo arms, and SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period in placebo arm.

Interventions

MEDI0382

MEDI0382 will be administered subcutaneously, 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 Type: DRUG

Placebo

Placebo will be administered subcutaneously for 16 days in the single-blind treatment period in both MEDI0382 and placebo arms, and SC injection of placebo matched to MEDI0382 for 42 days in double-blind treatment period in placebo arm.

Intervention Type: DRUG

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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MedImmune LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Cambridge, , United Kingdom

Countries

United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

D5670C00021

Identifier Type: -

Identifier Source: org_study_id