A Study for People With or Without Type 2 Diabetes Who Are Overweight or Obese

Do you have type 2 diabetes and are currently struggling with weight and blood sugar related issues?

This clinical research study is evaluating an experimental treatment for type 2 diabetics.

Would you like to take part?

As a volunteer in a research study, you’ll receive study-related medical care from the study doctor and regular follow-up of your health to monitor the effectiveness of the care you’ll receive. The results of this research will be used to find out if the investigational medication being studied will be of benefit to others struggling to manage obesity, and whether it will be made widely available to all Canadians. Study volunteers are an important part of moving medical care forward.

You may qualify to participate in this study if you:

• Are a male or post-menopausal female aged 18 through 65 years at the time of screening.
• For parts A, B, C only: Participants with or without T2DM. If participants have a diagnosis of T2DM, the glucose control managed with diabetes diet and in addition to metformin treatment no more than two treatment options (with a stable dose 3 months prior to screening).For part D only: Participants who are diagnosed with T2DM, have inadequate glycemic control with diet and exercise. Participants who are prescribed an oral anti-diabetic agent such as metformin, a DPP IV inhibitor, sulphonylurea, glinides, alphaglucosidase inhibitors, and an SGLT2 inhibitor may be eligible to enter the study following a washout of 4-weeks or 5-half lives (whichever is longer) washout period.
• Have a screening HbA1c value within the target range of
  • ≥ 42 to ≤ 75 mmol/mol (6% to 9%) for T2DM patients
  • < 48 mmol/mol (< 6.5%) for participants without T2DM
• Have a BMI greater than or equal to 27 kg/m^2, and less than 39.9 kg/m^2 (You can calculate your BMI using this tool: https://www.nhlbi.nih.gov/health/educational/lose_wt/BMI/bmicalc.htm)
• Provide written informed consent and any locally required authorization (eg, European Union Data Privacy Directive) obtained from the participant prior to performing any protocol-related procedures, including screening evaluations
• Have the ability to complete and meet all eligibility requirements for randomization within 60 days after signing the ICF.
• Have venous access suitable for multiple cannulations.
• Are willing and able to self-administer weekly SC injections (Parts C and D only)

You may not qualify to participate if you:

• Have T2DM currently treated with insulin.
• Have T2DM currently treated with more than 3 anti-diabetic therapies.
• Participants with or without T2DM treated with a GLP-1RA within 3 months of screening.
• Have a 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.
• Have 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.
• Have a 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.
• Have a history of cancer within the last 10 years, with the exception of non-melanoma skin cancer.
• Have any clinically important illness (apart from T2DM), as judged by the investigator.
• Have any medical/surgical procedure, or trauma within 4 weeks prior to screening, at the discretion of the investigator.
• Show symptoms of insulinopenia or poor blood glucose control (eg, significant thirst, nocturia, polyuria, polydipsia, or weight loss).
• Test positive for hepatitis B or hepatitis C virus serology at screening.
• Test positive for human immunodeficiency virus test at screening or participant taking antiretroviral medications as determined by medical history or participant’s verbal report.
• Show 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.
• Have impaired renal function defined as estimated glomerular filtration rate (eGFR) ≤ 60 mL/minute/1.73m2 as defined by Chronic Kidney Disease Epidemiology Collaboration (2021).
• Have 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.
• Have any 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.
• HaveaAbnormal 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.
• Have 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.
• Have an implantable cardiac defibrillator or a permanent pacemaker, and participants with symptomatic tachy- or brady-arrhythmias.
• Have 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.
• Have a history of hospitalisation caused by heart failure or a diagnosis of heart failure.
• Have 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.
• Have a history of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity as judged by the investigator.
• Have participated in 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.
• Have any psychiatric illness such that participants have been committed to an institution by way of official or judicial order.
• Have a history of lactic acidosis or ketoacidosis.
• 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.
• Use drugs with enzyme inducing properties such as St John’s Wort within 3 weeks prior to the first administration of study intervention.
• Have 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.
• Have previously enrolled or randomized in the present study.
• Concurrently participate in another study of any kind.
• Ongoing participation in a 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.
• Are vegan, have 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).
• Excessively intake caffeine-containing drinks or food (eg, coffee, tea, Coca-Cola/Pepsi or similar drink type, chocolate) as judged by the investigator.
• Currently smoker or have smoked or used nicotine products (including e-cigarettes) within the previous 3 months prior to screening.
• 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).
• Are judged by the investigator not to participate in the study if unlikely to comply with study procedures, restrictions, and requirements.
• Have any 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)

There are other eligibility requirements that the study doctor will review. Only the study doctor can finally determine whether you are eligible to participate in the study or not.