The main aim of this study is to assess the effects of AZD0780 when added on top of ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.

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:

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

Inclusion Criteria:

1. Signed the informed consent form before any study-related procedure.
2. All females must have a negative serum pregnancy test at the Screening Visit and on admission to the Clinical Unit
3. Females of non-childbearing potential must be confirmed at the Screening Visit by fulfilling one of the following criteria: postmenopausal or surgically sterilized females.
4. Have a Body Mass Index (BMI) > 18 kg/m² and weigh at least 50 kg.
5. Sexually active fertile male participants with partners of childbearing potential must adhere to the contraception methods.
6. 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.
7. Fasting triglycerides < 400 mg/dL (or < 10.3 mmol/L for London EPCU) at the Screening Visit.

Exclusion Criteria:

1. History of any clinically important disease or disorder.
2. History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
3. Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
4. 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
5. 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
6. Any positive result on Screening for serum HBsAg, hepatitis B core antibody or human immunodeficiency virus.
7. 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.
8. Treatment with any lipid-lowering therapy or AZD0780 within the 3 months prior to Screening.
9. 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).

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.