A trial to learn how safe AZD9550 is in people with type 2 diabetes who are overweight or obese - CONTEMPO

Exclusion Criteria

• 1 Participants with T2DM treated with insulin.
• 2 Participants with T2DM treated with more than 3 anti-diabetic therapies.
• 3 Participants with T2DM treated with a GLP-1RA within 3 months of screening.
• 4 History of any clinically important disease or disorder which, in the opinion of the
• investigator, may either put the participant at risk because of participation in the study, or
• influence the results or the participant’s ability to participate in the study.
• 5 Serum calcitonin suggestive of thyroid C-cell hyperplasia (calcitonin level > 50 ng/L),
• medullary thyroid carcinoma, or history or family history of multiple endocrine neoplasia
• at screening.
• 6 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, as judged by the investigator.
• 7 History of cancer within the last 10 years, with the exception of non-melanoma skin
• cancer.
• 8 Any clinically important illness (apart from T2DM), as judged by the investigator.
• 9 Any medical/surgical procedure, or trauma within 4 weeks prior to screening, at the
• discretion of the investigator.
• 10 Symptoms of insulinopenia or poor blood glucose control (eg, significant thirst, nocturia,
• polyuria, polydipsia, or weight loss).
• 11 Positive hepatitis B or hepatitis C virus serology at screening.
• 12 Positive human immunodeficiency virus test at screening or participant taking
• antiretroviral medications as determined by medical history or participant’s verbal report.
• 13 At screening blood tests, any of the following:
• - AST ≥ 1.5 × ULN
• - ALT ≥ 1.5 × ULN
• - TBL ≥ 1.5 × ULN (with the exception of Gilbert’s syndrome)
• - Haemoglobin below the lower limit of the normal range or any other clinically
• significant haematological abnormality as judged by the investigator.
• 14 Impaired renal function defined as estimated glomerular filtration rate (eGFR)
• ≤ 60 mL/minute/1.73m2 as defined by Chronic Kidney Disease Epidemiology
• Collaboration (2021).
• 15 Any clinically important abnormalities in clinical chemistry, haematology, coagulation, or
• urinalysis results other than those specifically described as exclusion criteria herein, as
• judged by the investigator.
• 16 Significant late diabetic complications (macroangiopathy with symptoms of congestive
• heart disease or peripheral arterial disease, microangiopathy with symptoms of
• neuropathy, gastroparesis, retinopathy requiring treatment, nephropathy) detected in
• laboratory results or in clinical history/documentation as judged by the investigator.
• 17 Abnormal vital signs, after 10 minutes of supine rest, defined as any of the following:
• - Systolic BP < 90 mmHg or ≥ 150 mmHg
• - Diastolic BP < 50 mmHg or ≥ 90 mmHg
• - HR < 50 or > 85 bpm at resting state
• - Participants may be re-tested for the vital signs criteria only once if, in the
• investigator’s judgement, they are not representative of the participant.
• 18 Any clinically important abnormalities in rhythm, conduction, or morphology of the
• resting ECG and any abnormalities in the 12-lead ECG that, as considered by the
• investigator, may interfere with the interpretation of QTc interval changes, including
• abnormal ST-T-wave morphology or left ventricular hypertrophy.
• 19 Participants with implantable cardiac defibrillator or a permanent pacemaker, and
• participants with symptomatic tachy- or brady-arrhythmias.
• 20 Participants with unstable angina pectoris or stable angina pectoris classified higher than
• Canadian Cardiovascular Society class II or an acute coronary syndrome/acute
• myocardial infarction or coronary intervention with percutaneous coronary intervention or
• coronary artery bypass grafting or stroke within 6 months.
• 21 History of hospitalisation caused by heart failure or a diagnosis of heart failure.
• 22 Known or suspected history of drug abuse within the past 3 years as judged by the
• investigator and /or a positive screen for drugs of abuse at screening.
• 23 History of severe allergy/hypersensitivity or ongoing clinically important
• allergy/hypersensitivity as judged by the investigator.
• 24 Whole blood or red blood cell donation, or any blood loss > 500 mL (or > 400 mL in
• Part D) during the 3 months prior to screening.
• 25 Psychiatric illness such that participants have been committed to an institution by way of
• official or judicial order.
• 26 History of lactic acidosis or ketoacidosis.
• 27 Use of any of the following medicinal products:
• - Use of systemic corticosteroids within 28 days prior to screening.
• - Use of compounds known to prolong the QTc interval.
• - Use of any herbal preparations or medicinal products licensed for control of body
• weight or appetite within 3 months prior to screening.
• 28 Use of drugs with enzyme inducing properties such as St John’s Wort within 3 weeks
• prior to the first administration of study intervention.
• 29 Received another new chemical entity (defined as a compound that has not been approved
• for marketing), or has participated in any other clinical study that included drug treatment
• within at least 30 days or 5 half-lives prior to the first administration of study intervention
• in this study (whichever is longer). The period of exclusion to begin 30 days or 5 halflives
• of IMP after the final dose, or after the last visit, whichever is longest. Participants
• consented and screened, but not randomised into this study or a previous Phase 1 study,
• are not excluded.
• 30 Previous enrolment or randomisation in the present study.
• 31 Concurrent participation in another study of any kind is prohibited.
• 32 Ongoing weight loss diet (hypocaloric diet) or use of weight loss agents, unless the diet or
• treatment has been stopped at least 3 months prior to screening and the participant has had
• a stable body weight (± 5%) during the 3 months prior to screening.
• 33 Participants who are vegans, ones with medical dietary restrictions, or participants who
• are willingly conducting any diet likely to increase ketone levels (Atkins or any similar
• diet based on increased protein consummation or low carbohydrate content).
• 34 Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, Coca-Cola/Pepsi
• or similar drink type, chocolate) as judged by the investigator.
• 35 Current smokers or those who have smoked or used nicotine products (including
• e-cigarettes) within the previous 3 months prior to screening.
• 36 Participants who cannot communicate reliably with the investigator or vulnerable
• participants (eg, kept in detention, protected adults under guardianship, trusteeship, or
• committed to an institution by governmental or juridical order).
• 37 The participant is an employee, or close relative of an employee, of AstraZeneca, the
• CRO, or the study site, regardless of the employee’s role.
• 38 Judgement by the investigator that the participant should not participate in the study if the
• participant is unlikely to comply with study procedures, restrictions, and requirements.
• 39 Contra-indication to MRI: such as participants with pacemakers, metallic cardiac valves,
• magnetic material such as surgical clips, implanted electronic infusion pumps or other
• conditions that would preclude proximity to a strong magnetic field; participants with
• history of extreme claustrophobia or participant cannot fit inside the MRI scanner cavity
• (Parts B and C only).