A Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD1043 in Healthy Adult Participants Living With Overweight and/or Obesity.

This is a phase 1, first time in human (FTiH) randomized, single-blind, placebo-controlled study in healthy male and female participants living with overweight and/or obesity, with female participants being of non-childbearing potential. It consists of 2 parts:

Part A (single ascending doses: SAD): This will consist of Part A1 (Global SAD (GSAD)) with 6 cohorts, Part A2 (Japanese SAD (JSAD)) with 2 cohorts and Part A3 (Chinese SAD (CSAD)) with 1 cohort.

Part B (multiple ascending doses: MAD): This will consist of Part B1 (Global MAD (GMAD)) with 3 cohorts and Part B2 (Japanese MAD (JMAD)) with 1 cohort.

Participants are only allowed to participate in one of the cohorts.

Both Part A and Part B will comprise of:

• Screening period (up to 5 weeks).
• Treatment period.
• Safety follow-up period.

Inclusion criteria

• All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.
• Females of non-childbearing potential must be confirmed as postmenopausal or have documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy.
• Have a body mass index between 25 and 39.9 kg/m2 (Global cohorts [Parts A1 and B1]), or 23 and 39.9 kg/m2 (Japanese [Parts A2 and B2] and Chinese [Part A3] cohorts) inclusive and weigh at least 50 kg.
• For the Parts A2 and B2, participants should be Japanese (natives of Japan or Japanese Americans), having both parents and 4 grandparents who are Japanese. This includes healthy second and third generation participants of Japanese descent whose parents or grandparents are living in a country other than Japan.
• For the Part A3, participants should be Chinese defined as having both parents and 4 grandparents who are ethnically Chinese. This includes second and third generation Chinese whose parents or grandparents are living in a country other than China.

Exclusion criteria

• History of any clinically important disease or disorder.
• 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 study intervention.
• Any clinically important abnormalities in laboratory values, clinical chemistry, hematology, urinalysis results, or vital signs.
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity to drugs of a similar class to AZD1043.
• Has received prescription, non-prescription, or experimental medications for weight loss within 3 months prior to the Screening Visit.
• History of psychosis or bipolar disorder or major depressive disorder within the past 2 years with the participant being clinically unstable.