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

A Phase 1, Randomized, Single-blind, Placebo-controlled Study to Investigate the Pharmacokinetics, Safety, Tolerability, and Efficacy of AZD0780 in Combination With Ezetimibe, Ezetimibe/Rosuvastatin, or Ezetimibe/Bempedoic Acid in Healthy Male and Female Participants 18 to 75 Years of Age With Elevated LDL-C.

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.

Study Overview

• Status: Completed
• Conditions: Dyslipidemia
• Intervention / Treatment: Drug: Placebo; Drug: AZD0780; Drug: Ezetimibe; Drug: Rosuvastatin; Drug: Bempedoic Acid

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Harrow, United Kingdom, HA1 3UJ
    • Research Site
• United States
  • California
    • Glendale, California, United States, 91206
      • Research Site
  • Maryland
    • Brooklyn, Maryland, United States, 21225
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ezetimibe + AZD0780; Participants will receive ezetimibe 10 mg and AZD0780 once daily (QD) for 4 weeks.	Drug: AZD0780; AZD0780 tablet will be administered orally.; Drug: Ezetimibe; Ezetimibe tablet will be administered orally.
Experimental: Rosuvastatin + Ezetimibe + AZD0780; Participants will receive rosuvastatin 20 mg, ezetimibe 10 mg and AZD0780 QD for 4 weeks.	Drug: AZD0780; AZD0780 tablet will be administered orally.; Drug: Ezetimibe; Ezetimibe tablet will be administered orally.; Drug: Rosuvastatin; Rosuvastatin tablet will be administered orally.
Experimental: Bempedoic Acid + Ezetimibe + AZD0780 (Optional Cohort); Participants will receive bempedoic acid 180 mg, ezetimibe 10 mg and AZD0780 QD for 4 weeks.	Drug: AZD0780; AZD0780 tablet will be administered orally.; Drug: Ezetimibe; Ezetimibe tablet will be administered orally.; Drug: Bempedoic Acid; Bempedoic Acid tablet will be administered orally.
Placebo Comparator: Ezetimibe + Placebo; Participants will receive ezetimibe 10 mg and placebo QD for 4 weeks.	Drug: Placebo; Placebo will be administered orally.; Drug: Ezetimibe; Ezetimibe tablet will be administered orally.
Placebo Comparator: Rosuvastatin + Ezetimibe + Placebo; Participants will receive rosuvastatin 20 mg, ezetimibe 10 mg and placebo QD for 4 weeks.	Drug: Placebo; Placebo will be administered orally.; Drug: Ezetimibe; Ezetimibe tablet will be administered orally.; Drug: Rosuvastatin; Rosuvastatin tablet will be administered orally.
Placebo Comparator: Bempedoic Acid + Ezetimibe + Placebo (Optional Cohort); Participants will receive bempedoic acid 180 mg, ezetimibe 10 mg and placebo QD for 4 weeks.	Drug: Placebo; Placebo will be administered orally.; Drug: Ezetimibe; Ezetimibe tablet will be administered orally.; Drug: Bempedoic Acid; Bempedoic Acid tablet will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in direct Low-density Lipsprotein Cholesterol (LDL-C)	To evaluate the effect of AZD0780 on LDL-C levels versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.	Week 4
Number of participants with adverse events	The safety and tolerability of AZD0780 when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid will be assessed.	From screening (Day -56 to -29) to 14 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma concentration of AZD0780	To further characterize AZD0780 pharmacokinetics (PK) in plasma.	From Day 1 to Day 42
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)	To further characterize AZD0780 PK in plasma.	From Day 1 to Day 42
Area under concentration-time curve in the dosing interval (AUCtau) (Day 15)	To further characterize AZD0780 PK in plasma.	From Day 1 to Day 42
Maximum observed drug concentration (Cmax)	To further characterize AZD0780 PK in plasma.	From Day 1 to Day 42
Time to reach maximum observed concentration (tmax)	To further characterize AZD0780 PK in plasma.	From Day 1 to Day 42
Change from baseline in LDL-C ultra	To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.	Week 4
Change from baseline in LDL-C Friedewald	To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.	Week 4
Change from baseline in total cholesterol	To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.	Week 4
Change from baseline in non- HDL-C (high-density lipoprotein-cholesterol)	To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.	Week 4
Change from baseline in HDL-C	To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.	Week 4
Change from baseline in triglycerides	To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.	Week 4
Change from baseline in in Lipoprotein A [Lp(a)]	To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.	Week 4
Change from baseline in Apolipoprotein B (ApoB)	To evaluate the effect of AZD0780 on lipid parameters and inflammatory markers versus placebo when dosed with ezetimibe or ezetimibe and rosuvastatin or ezetimibe and bempedoic acid.	Week 4

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2024
• Primary Completion (Actual): October 29, 2025
• Study Completion (Actual): October 29, 2025

Study Registration Dates

• First Submitted: December 16, 2024
• First Submitted That Met QC Criteria: December 16, 2024
• First Posted (Actual): December 19, 2024

Study Record Updates

• Last Update Posted (Actual): November 10, 2025
• Last Update Submitted That Met QC Criteria: November 6, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Hypercholesterolemia; LDL-C; Cholesterol absorption inhibitor; ATP-citrate lyase inhibitor
• Additional Relevant MeSH Terms: Metabolic Diseases; Hyperlipidemias; Lipid Metabolism Disorders; Nutritional and Metabolic Diseases; Hypercholesterolemia; Dyslipidemias; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Hydrocarbons; Amides; Pyrimidines; Hydrocarbons, Halogenated; Sulfonamides; Sulfones; Azetidines; Azetines; Fluorobenzenes; Hydrocarbons, Fluorinated; Rosuvastatin Calcium; Ezetimibe; 8-hydroxy-2,2,14,14-tetramethylpentadecanedioic acid
• Other Study ID Numbers: D7960C00017

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

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.

• IPD Sharing Time Frame: 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.
• IPD Sharing Access Criteria: 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.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No