A Study to Evaluate the Effect of MEDI0382 on Energy Balance in Overweight and Obese Participants With Type 2 Diabetes Mellitus
Condition: Diabetes Mellitus, Type II; Obesity
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Overweight
Intervention: MEDI0382; Placebo
Intervention description: 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 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Randomised, Double-Blind, Placebo-Controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 28.0
Sex: All
Minimum age: 30 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Diabetes Mellitus, Type II; Obesity; MEDI0382

Summary:

      An exploratory 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