A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD6234 After Repeat Dose Administration in Participants Who Are Overweight or Obese

The study will comprise of:

• A Screening Period of maximum 32 days (from Day -35 to Day -3).
• A Treatment Period of 6 weeks (Cohort 1), 12 weeks (Cohort 2 and 3) and 26 weeks (Cohort 4) during which the participants will receive the study drug during residency at clinical unit.
• A Follow-up Visit after the last dose of study drug.

This study with repeated dosing of AZD6234 consists of 4 cohorts. For cohorts 1,2 and 3, eligible participants will be randomized to AZD6234 and placebo in a 3:1 ratio. For Cohort 4, eligible participants will be randomized in a 4:1:4:1 ratio.

Inclusion criteria

• Healthy male and female participants aged 18 to 55 years with suitable veins for cannulation or repeated venipuncture.
• All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit, must not be lactating and must be of non-childbearing potential, confirmed at the Screening Visit by fulfilling one of the following criteria:

• Postmenopausal defined as amenorrhea for at least 12 months or more following cessation of all exogenous hormonal treatments and FSH levels in the postmenopausal range.
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy but not tubal ligation.
• Have a BMI between 25 and 40 kg/m2 inclusive (at the time of screening) and weigh at least 60 kg.
• Participant must have an evaluable, pre-randomization MRI, as confirmed by the core laboratory review (Cohort 4 only).
• Cohort 4 only: Females of childbearing potential who use adequate protection (oral contraceptives are not permitted).

Exclusion criteria

• 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.
• History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of IMP.
• Any clinically important abnormalities in rhythm, conduction or morphology of the resting ECG and any clinically important abnormalities in the 12-lead ECG as considered by the Investigator that may interfere with the interpretation of QTc interval changes, including abnormal STT wave morphology, particularly in the protocol defined primary lead or left ventricular hypertrophy.
• Known or suspected history of drug abuse, smoking, alcohol abuse or cotinine at screening.
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the Investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD6234.
• Has received prescription or non-prescription medication for weight loss within the last 3 months.
• Self-reported weight change of > 5 kg in the last 3 months prior to screening.
• Previous or planned (within study period) bariatric surgery or fitting of a weight loss device (eg, gastric balloon or duodenal barrier).
• Participants who follow vegan diet or have medical dietary restrictions.
• Participants who cannot communicate reliably with the Investigator.
• Vulnerable participants, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.
• 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 (Cohort 4 only).