The aim of this study is to evaluate the safety and tolerability, and pharmacodynamics (PD) of AZD4144 administered as repeated daily oral dosing.

This is placebo-controlled, parallel group and single centre study in healthy male and female participants with obesity and no known Atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or Type 2 Diabetes Mellitus.

Participants will be randomized in the ratio of 1:1 to receive either AZD4144 or placebo.

This study will comprise of:

• A screening period of 28 days.
• The treatment duration will be up to 28 days.
• The visit frequency will be weekly up to a Follow-up Visit, followed by a Final Follow-up Visit 28 days after the final dose of AZD4144.

Key Inclusion Criteria:

• Serum hsCRP > 2 milligrams per liter (mg/L).
• All females must have a negative pregnancy test at the Screening Visit and at the randomization visit (Visit 2).
• Females of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception to avoid pregnancy from the time of first administration of study intervention until 3 months after the Final Follow-up Visit.
• Have a body mass index (BMI) greater than or equal to (≥) 30 and less than or equal to (≤) 45 kilograms per meter^2 (kg/m^2).

Key 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 of Myocardial infarction (MI), coronary revascularisation, stroke, revascularisation for peripheral arterial disease, or other pre-existing Cardiovascular (CV) diseases.
• History of Diabetes (Type 1 and Type 2) or glycated haemoglobin (HbA1c) ≥6.5%.
• 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 skin disorder, history of, or ongoing clinically significant allergy/hypersensitivity.
• Clinically significant serious active and chronic infections within 60 days prior to randomization.
• Known history of primary immunodeficiency (congenital or acquired) or an underlying condition that predisposes to infection.

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 approved.

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