The purpose of the study is to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of AZD1043 following single and multiple ascending doses in healthy adult participants living with overweight and/or obesity, including participants of Japanese and Chinese descent.

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.

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org.

Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.