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

AstraZeneca

Status and phase: Enrolling; Phase 1

Conditions: Dyslipidemia

Treatments: Drug: Rosuvastatin; Drug: Bempedoic Acid; Drug: Placebo; Drug: AZD0780; Drug: Ezetimibe

Study type: Interventional

Funder types: Industry

Identifiers

NCT06742853

D7960C00017

Details and patient eligibility

About

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.

Full 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: Accepts Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

---

120 participants in 6 patient groups, including a placebo group

Ezetimibe + AZD0780

Experimental group

Description:

Participants will receive ezetimibe 10 mg and AZD0780 once daily (QD) for 4 weeks.

Treatment:

Drug: Ezetimibe

Drug: AZD0780

Rosuvastatin + Ezetimibe + AZD0780

Experimental group

Description:

Participants will receive rosuvastatin 20 mg, ezetimibe 10 mg and AZD0780 QD for 4 weeks.

Treatment:

Drug: Ezetimibe

Drug: AZD0780

Drug: Rosuvastatin

Bempedoic Acid + Ezetimibe + AZD0780 (Optional Cohort)

Experimental group

Description:

Participants will receive bempedoic acid 180 mg, ezetimibe 10 mg and AZD0780 QD for 4 weeks.

Treatment:

Drug: Ezetimibe

Drug: AZD0780

Drug: Bempedoic Acid

Ezetimibe + Placebo

Placebo Comparator group

Description:

Participants will receive ezetimibe 10 mg and placebo QD for 4 weeks.

Treatment:

Drug: Ezetimibe

Drug: Placebo

Rosuvastatin + Ezetimibe + Placebo

Placebo Comparator group

Description:

Participants will receive rosuvastatin 20 mg, ezetimibe 10 mg and placebo QD for 4 weeks.

Treatment:

Drug: Ezetimibe

Drug: Placebo

Drug: Rosuvastatin

Bempedoic Acid + Ezetimibe + Placebo (Optional Cohort)

Placebo Comparator group

Description:

Participants will receive bempedoic acid 180 mg, ezetimibe 10 mg and placebo QD for 4 weeks.

Treatment:

Drug: Ezetimibe

Drug: Placebo

Drug: Bempedoic Acid