A study to investigate the effect of MEDI0382 on hepatic glycogen metabolism in overweight and obese subjects with Type 2 Diabetes Mellitus.

Exclusion Criteria

• -Any subject who has received another investigational product as part
• of a clinical study or a 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
• - Any subject who has received any of the following medications prior to the start of the study:
• • 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
• • Glucagon
• •Warfarin
• -Any contraindication to magnetic resonance imaging/MRS scanning
• including claustrophobia or dislike of confined spaces
• - Symptoms of acutely decompensated blood glucose control (eg, thirst,
• polyuria, weight loss), a history of type 1 diabetes mellitus (T1DM) or
• diabetic ketoacidosis, or if the subject has been treated with daily SC
• insulin within 90 days prior to screening
• - Recurrent unexplained hypoglycaemic episodes (defined as glucose <
• 3.0 mmol/L or < 54 mg/dL on more than 2 occasions in 6 months prior
• to screening)
• - Significant inflammatory bowel disease, gastroparesis, or other severe
• disease or surgery affecting the upper GI tract (including weightreducing
• 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 NASH or nonalcoholic fatty
• liver disease without portal hypertension or cirrhosis) and/or subjects
• 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) < 30 mL/minute/1.73m2 at screening (glomerular filtration
• rate estimated according to Modification of Diet in Renal Disease (MDRD)
• using MDRD Study Equation IDMS-traceable (International System of
• Units [SI] units)
• - Poorly controlled hypertension defined as:
• • Systolic blood pressure (BP) > 180 mm Hg
• • Diastolic BP > 105 mm Hg
• After 10 minutes of supine rest and confirmed by repeated measurement
• at screening.
• - Unstable angina pectoris, myocardial infarction, transient ischemic
• attack or stroke within 3 months prior to screening, or subjects 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 (defined as > 21 units per week for a male subject, and
• >14 units per week for a female subject). Subjects must have a negative
• alcohol test result at screening and prior to randomisation.