A Phase I/II, Randomised, Single-blind, Placebo-controlled, Multiple-ascending-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD9550 Monotherapy and Co-administration of AZD9550 and AZD6234 in Participants Living With Obesity and Overweight With or Without Type 2 Diabetes Mellitus
AZD9550, previously being developed for the treatment NASH, is a dual GCG and GLP-1 receptor agonist. AZD9550 is now being developed in combination with AZD6234, a SARA, for the treatment of overweight and obesity and its associated co-morbidities. Co-administration of AZD9550 and AZD6234 is currently being evaluated in participants living with obesity and overweight without T2DM in an ongoing Phase 2b study. The purpose of this study is to investigate the safety, tolerability, and effects of increasing doses of AZD9550 monotherapy in overweight and obese participants aged 18 through 65 years living with or without T2DM, and to investigate how AZD9550 is absorbed, distributed, and eliminated from the body (Parts A-D). In addition, the study will investigate the safety and tolerability of co-administration of AZD9550 and AZD6234 in participants living with T2DM with obesity or overweight aged 18 through 75 years (Part E).
• Males or females aged 18 through 65 years (Parts A-D) or 75 years (Part E) at the time of screening.
• 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).
• Part D only: Participants who are diagnosed with T2DM, have inadequate glycaemic 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.
• Part E only: Participants are eligible to be included in the Part E only if they meet all of the following criteria at screening:
⁃ Diagnosed with T2DM.
⁃ Are treated with diet and exercise only, or any combination of OAD with stable doses in the 3 months prior to dosing.
⁃ Participants prescribed a DPP IV inhibitor or a GLP-1RA-containing medicine, alone or in combination with other OADs, may be eligible to enter the study if they have not been treated with any of these drugs for at least 35 days or 5 drug half-lives (whichever is longer) prior to randomisation.
• Participants with a screening HbA1c value within the target range of
• • ≥ 42 to ≤ 86 mmol/mol (6% to 10%).
• Body mass index from ≥27 (≥25 in Part D) to ≤39.9 kg/m2 (inclusive) (Part A-D) or ≥ 27 kg/m2 (Part E).
• Contraceptive use by males or females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• 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
• Ability to complete and meet all eligibility requirements for randomisation within 60 days after signing the ICF.
• Venous access suitable for multiple cannulations.
• Willing and able to self-administer weekly SC injections (Parts C, D and E only).