This is a Phase I, First In Human (FIH), randomized, single-blind, placebo-controlled, study in healthy male and/or female subjects of non-childbearing potential including healthy subjects of Chinese and Japanese ethnicity performed at multiple centers (up to 4 study centers).~56 subjects have been planned for Part A and 76 subjects for Part B.~Part A:~A Screening Period of maximum 28 days.~Admission to study center (Day -1 or Day -2).~A Treatment Period (Day 1 to Day 3) with a single dose of AZD0780 or placebo on Day 1. Subjects will be discharged on Day 3.~A Follow-up Visit within 5 to 7 days after the Investigational Medicinal Product (IMP) dose for all cohorts.~An additional Follow-up Visit within 9 to 11 days after the IMP dose from Cohort 3 onwards.~(i) Part A1 - Up to 5 dose cohorts of AZD0780 are planned to be investigated. Depending on the findings, up to 4 additional dose cohorts may be added. Within each cohort, 6 subjects will be randomized to receive AZD0780, and 2 subjects randomized to receive placebo. Dosing for each ascending dose cohort will proceed with 2 subjects in a sentinel sub-cohort such that one subject will be randomized to receive AZD0780, and one subject will be randomized to receive placebo.~(ii) Part A2 - The subjects from a chosen cohort in Part A1 will return to the study center no sooner than 9 days after the first dose administration of IMP and will receive AZD0780 or placebo after intake of a high-calorie, high-fat breakfast, to assess the effect of food on the PK of AZD0780.~The subjects will stay at the study center until 48 hours post-dose in both the parts.~• Part B:~Global Multiple Ascending Dose (MAD) cohort - Up to 3 dose cohorts are planned to be investigated. In each cohort, 20 subjects will participate and receive either AZD0780 or placebo, randomized 3:1 for 28 days dosing. Depending on the findings, 3 additional dose levels may be added in up to 3 additional cohorts (up to 20 subjects per cohort).~Japanese Single and Multiple Ascending Dose (JSMAD) cohort - Two cohorts are planned. One cohort of 8 Japanese subjects will receive a medium dose level of AZD0780 or placebo randomized 3:1 for 9 days dosing (subjects will receive a single dose of IMP on Day 1 followed by daily dosing on Days 8 to 15 [there is no dose on Days 2 to 7]). The second cohort of 8 Japanese subjects will receive a higher dose level of AZD0780 or placebo.
This study will assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AZD0780 following single and multiple dose administration to healthy subjects with or without elevated Low-Density Lipoprotein-Cholesterol (LDL-C) levels.~This study will consist of two parts (Parts A and B).~56 subjects have been planned for Part A and 76 subjects for Part B. Additional subjects may be included for the optional cohorts depending upon emerging data.