This study will evaluate safety, tolerability and pharmacokinetics (PK) of AZD7503, following subcutaneous (SC) administration of single ascending doses of AZD7503 in healthy participants.

This is a Phase I, First-in-Human, study in healthy males and females (non-childbearing potential) participants. In this study up to four dose levels of AZD7503 are planned to be evaluated.

The planned doses of AZD7503 are dose 1, dose 2, dose 3, and dose 4. Eligible participants will be randomised to receive either AZD7503 or placebo. The study will include four single dose cohorts with an option to include two cohorts based on emerging data from planned cohorts in the study and two additional cohorts of Japanese participants and one cohort of Chinese participants will also be included.

Dosing for each ascending dose cohort will be proceeded with sentinel dosing strategy. Here, sentinel sub-cohort will be included, such that 1 participant will be randomised to receive placebo and 1 participant will be randomised to receive AZD7503. The safety data from the sentinel participants up to 24 hours post-dose will be reviewed by the Principal Investigator (PI) before the remaining participants in the cohort are dosed

The study will comprise:

• A Screening Period of maximum 28 days;
• A Treatment Period during which participants will be resident at the Study Centre from the day before study medication administration (Day -1) until at least 72 hours after study medication administration; discharged from the Study Centre on Day 4;
• Follow-up Visits on 1,2,4,6 and 8 weeks; and
• A Final Follow-up Visit 10 weeks after the last study medication dose. Each participant will be involved in the study for approximately 14 weeks.

Inclusion Criteria:

• Healthy non smoking male and/or female (of non childbearing potential) participants with suitable veins for cannulation or repeated venipuncture.

• Females must have a negative pregnancy test at screening and on admission to the study centre, must not be lactating and must be of non childbearing potential.

• Body mass index (BMI) between 18 and 30 kg/m^2, inclusive, and weigh at least 60 kg for healthy participants or between 18 and 32 kg/m^2, inclusive, and weigh at least 50 kg for Japanese and Chinese participants.

• For Japanese and Chinese participants:

  1. A Japanese participant is defined as having both parents and 4 grandparents who are ethnically Japanese. This includes first-, second-and third-generation Japanese whose parents or grandparents are living in a country other than Japan.
  2. A Chinese participant is defined as having both parents and 4 grandparents who are ethnically Chinese. This includes first-, second-and third-generation Chinese whose parents or grandparents are living in a country other than China.

• Willing to participate in retrospective genotyping analysis for HSD17B13.

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 administration of study intervention.

• Any laboratory values with the following deviations at screening and/or Day 1:

  • Alanine aminotransferase > Upper Limit of Normal (ULN)
  • Aspartate aminotransferase > ULN
  • Total bilirubin > ULN
  • Creatinine > ULN
  • White blood cell count < Lower Limit of Normal (LLN)
  • Hemoglobin < LLN
  • Estimated glomerular filtration rate < 60 mL/min/1.73 m^2
  • Platelets >ULN and/or \

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. 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 Pharma 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 de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

This study is single blind with regard to treatment (AZD7503 or placebo). This means that the participant and the study centre staff will remain blinded during the dosing phase of the study and the randomisation code will only be available at each pre defined decision point before the Safety Review Committee meeting in order to review the data unblinded.