This is a Multi-centre, Multi-drug, Platform Study in Chinese Participants Living With Obesity / Overweight

This is a Phase Ⅱa, multi-centre, multi-drug, platform study in Chinese participants living with obesity/overweight. This platform study will consist of several sub-studies. Eligible participants will be allocated to one sub-study to receive the study intervention(s). Each sub-study will consist of a screening period, a treatment period, and a follow-up period.

Sub-study 1: AZD6234 Monotherapy This study will explore the safety, tolerability, pharmacokinetic (PK), efficacy, and immunogenicity of AZD6234 in Chinese participants with obesity/overweight, approximate 18 participants will be randomised in sub-study 1. The sub-study will comprise 3 periods totalling up to approximately 23 weeks.

Sub-study 2: AZD9550 Monotherapy and AZD6234 in combination with AZD9550 This study will explore the safety, tolerability, PK, efficacy, and immunogenicity of AZD9550 and of AZD6234 in combination with AZD9550 in Chinese participants with obesity/overweight, approximately 30 participants will be randomised in sub-study 2 (15 in Cohort A and 15 in Cohort B). The sub-study will comprise 3 periods totalling up to approximately 35 weeks.

Inclusion criteria

• Age 18 to 55 years.
• BMI ≥ 27 kg/m2.
• Stable body weight for 3 months prior to screening.
• Male and female (Contraceptive use by participants or participant partners should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies).
• Participants should refrain from blodd donation throughout the sub-study, including the follow-up period.
• Negative pregnancy test at screening and randomisation for FOCBP and must not be breastfeeding.

Exclusion criteria

• Have received prescription medication or non-prescription medication for weight loss within the last 3 months prior to screening.
• History of type 1 or type 2 diabetes mellitus or symptoms indicative of insulinopenia or poor glucose control.
• Treatment with diabetes medication in past 3 months prior to screening.
• HbA1c ≥ 6.5% (48 mmol/mol) at screening.
• Gastroparesis (or similar) requiring treatment.
• Significant inflammatory bowel disease or other severe disease or surgery affecting the upper GI tract.
• Significant hepatic disease (except for non-alcoholic steatohepatitis or non-alcoholic fatty liver disease without portal hypertension or cirrhosis) and/or participants with any of the following results at screening:

• AST ≥ 2.5 × ULN
• ALT ≥ 2.5 × ULN
• TBL ≥ 1.5 × ULN.
• Prior history of cholecystectomy or untreated cholelithiasis.
• History of acute or chronic pancreatitis or pancreatic amylase or lipase > 2 × ULN at screening.
• Severely uncontrolled hypertension defined as systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 100 mmHg on the average of 2 seated measurements after being at rest for at least 5 minutes.
• HR < 50 bpm or > 100 bpm after being at rest for 5 minutes.
• Impaired renal function defined as eGFR ≤ 45 mL/minute/1.73 m2 at screening (GFR estimated according to CKD-EPI).
• History of psychosis or bipolar disorder.
• Severe vitamin D deficiency defined as a 25-OH vitamin D level < 12 ng/mL.
• Uncontrolled thyroid disease, defined as TSH > ULN or < LLN for the laboratory reference range, as judged by the PI at screening.

Sub-study 2 only

• Personal or family history (first-degree relative) of MTC or MEN2.
• History of marijuana or THC use within 3 months before screening, or unwilling/unable to abstain from marijuana or THC use during the study.
• Previous hospitalisation for any psychiatric reason.
• PHQ-9 score ≥ 15 within the 2 years prior to screening or at screening.