A Study to Evaluate the Safety and Pharmacokinetics of MEDI0382 in Overweight/Obese Subjects of Japanese or Chinese Descent

Exclusion Criteria

• Any of the following would exclude the subject from participation in the study:
• 1) Any condition that, in the opinion of the investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or study results. Specific
• examples are:
• a. Past history of acute or chronic pancreatitis, or pancreatic amylase or
• lipase greater than twice the upper limit of normal (ULN) at screening.
• b. Past history of gastroparesis requiring treatment.
• c. Past history of surgery affecting the upper GI tract likely to affect the
• interpretation of safety and tolerability data.
• d. History of cholelithiasis leading to episodes of acute cholecystitis not
• treated by cholecystectomy, or known biliary disease.
• e. History of or family history of multiple endocrine neoplasia type 2; or
• serum calcitonin suggestive of thyroid C-cell hyperplasia (calcitonin
• level > 50 ng/L); or medullary thyroid carcinoma at screening.
• f. Past history of clinically significant cardiac rhythm disturbance (eg,
• permanent or paroxysmal atrial fibrillation/flutter, paroxysmal
• supraventricular tachycardia, paroxysmal ventricular tachycardia,
• presence of an implantable pacemaker device or
• cardioverter/defibrillator).
• g. History of treated or symptomatic cardiac failure.
• h. Impaired renal function, defined as estimated glomerular filtration rate
• < 60 mL/minute/1.73 m2 at screening.
• 2) History of previous myocardial infarction or cerebrovascular accident (eg, stroke).
• 3) History or presence of GI, renal, or hepatic disease (with the exception of Gilbert’s syndrome), or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• 4) History of cancer, with the exception of non-melanoma skin cancer.
• 5) Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks prior to dosing.
• 6)Positive hepatitis B surface antigen or hepatitis C virus antibody serology at screening.
• 7) Positive human immunodeficiency virus test at screening or use of antiretroviral medications as determined by medical history or subject’s verbal report.
• 8) Any of the following based on screening blood tests:
• a. Aspartate aminotransferase (AST) ≥ 1.5 × ULN.
• b. Alanine aminotransferase (ALT) ≥ 1.5 × ULN.
• c. Total bilirubin ≥ 1.5 × ULN.
• d. Hemoglobin below 12 g/dL.
• e. Neutrophils < 1.5 × 10^9/L.
• f. Thyroid stimulating hormone level above the normal range.
• 9) Use of any of the following medicinal products:
• a. Concurrent or previous use of a GLP-1 receptor agonist.
• b. Current or previous use of systemic corticosteroids within the past 28
• days prior to screening.
• c. Use of any licensed medicinal products, or herbal preparations for
• control of body weight or appetite, is prohibited from one week prior to
• Day -1 through Day 3.
• 10) Abnormal vital signs after 10 minutes of supine rest, defined as any of the following:
• a. Systolic BP < 90 mmHg or ≥ 140 mmHg.
• b. Diastolic BP < 50 mmHg or ≥ 90 mmHg.
• c. Heart rate < 45 or > 85 beats per minute.
• 11) Any clinically important abnormalities in rhythm, conduction (eg, Wolff-Parkinson-White syndrome, sick-sinus syndrome), or morphology of the resting 12-lead ECG, or any abnormalities in the ECG that, in the opinion of the investigator, may interfere with the interpretation of changes in the QTc, including abnormal T-wave morphology, or left ventricular hypertrophy.
• 12) Prolonged QTc using the Fridericia formula (QTcF) > 450 milliseconds, or shortened QTcF < 340 milliseconds based on 12-lead ECG, or family history of long QT syndrome.
• 13) PR (PQ) interval shortening < 120 milliseconds (PR < 120 but > 110 milliseconds is acceptable if there is no evidence of ventricular pre excitation).
• 14) PR (PQ) interval prolongation (> 240 milliseconds), intermittent second degree block (Wenckebach block while asleep is not exclusive) or third degree block, or atrioventricular dissociation.
• 15) Complete or intermittent complete bundle branch block, incomplete bundle branch block,or intraventricular conduction delay with QRS > 110 milliseconds. Subjects with QRS > 110 but < 115 milliseconds are acceptable if there is no evidence of ventricular hypertrophy.
• 16) Known or suspected history of drug abuse within the past 3 years as judged by the investigator.
• 17) History of alcohol abuse or excessive intake of alcohol within the past 3 years as judged by the investigator.
• 18) Positive screen for drugs of abuse or positive breath test for alcohol at screening. Subjects who use benzodiazepines for chronic anxiety or sleep disorders may be permitted to enter the study.
• 19) History of severe allergy/hypersensitivity or ongoing clinically important
• allergy/hypersensitivity as judged by the investigator.
• 20) Whole blood or red blood cell donation, or any blood loss > 500 mL within 2 months prior to screening.
• 21) Receipt of another new chemical entity (defined as a compound that has not been approved for marketing), or participation in any other clinical study that included drug treatment within at least 30 days or 5 half-lives of the administration of investigational product in this study (whichever is longer). The period of exclusion will end 30 days or 5 half-lives of investigational product after the final dose, whichever is longest. Subjects consented and screened, but not randomized into this study or a previous study, will not be excluded.
• 22) Psychiatric illness such that subjects have been committed to an institution by way of official or judicial order.
• 23) The subject is an employee, or close relative of an employee, of AstraZeneca, MedImmune, the CRO, or the study site, regardless of the employee’s role.