A Study to Investigate the Pharmacokinetics, Safety, Tolerability, and Efficacy of AZD0780 With Ezetimibe Combinations in Healthy Adults With Elevated LDL-C.

This is a randomized, single-blind, placebo-controlled study in healthy participants with elevated low-density lipoprotein-cholesterol (LDL-C).

This study will assess the pharmacokinetic (PK), safety, tolerability, and efficacy of AZD0780 in combination with ezetimibe, ezetimibe/rosuvastatin, and ezetimibe/bempedoic acid.

Participants will be randomized to receive either AZD0780 or placebo (to be administered with ezetimibe, ezetimibe/rosuvastatin, or ezetimibe/bempedoic acid).

The study will comprise:

• A Screening Period of up to 28 days.
• A Run-in Period of 28 days.
• A Treatment Period of 28 days.
• Two Follow-up Visits, one and two weeks after the last dose of study drug.

Inclusion criteria

• Signed the informed consent form before any study-related procedure.
• All females must have a negative serum pregnancy test at the Screening Visit and on admission to the Clinical Unit
• Females of non-childbearing potential must be confirmed at the Screening Visit by fulfilling one of the following criteria: postmenopausal or surgically sterilized females.
• Have a Body Mass Index (BMI) > 18 kg/m² and weigh at least 50 kg.
• Sexually active fertile male participants with partners of childbearing potential must adhere to the contraception methods.
• Fasting LDL-C > 100 mg/dL but < 190 mg/dL (> 2.6 mmol/L but < 4.9 mmol/L for London EPCU) at the Screening Visit.
• Fasting triglycerides < 400 mg/dL (or < 10.3 mmol/L for London EPCU) at the Screening Visit.

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 laboratory values with specific deviations in alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TBL), estimated glomerular filtration rate, or hemoglobin at the Screening Visit or on Admission
• Any clinically important abnormalities in clinical chemistry, hematology, or urinalysis results other than those described under exclusion criterion number 4, at Screening and/or Admission to the Clinical Unit
• Any positive result on Screening for serum HBsAg, hepatitis B core antibody or human immunodeficiency virus.
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, as judged by the investigator or history of hypersensitivity to drugs with a similar chemical structure or class to AZD0780, ezetimibe, rosuvastatin, and bempedoic acid.
• Treatment with any lipid-lowering therapy or AZD0780 within the 3 months prior to Screening.
• Treatment with drugs for reduction or inhibition of Proprotein convertase subtilisin/kexin type 9 (PCSK9) within the last 12 months prior to Screening (approved or investigational and apart from AZD0780).