Clinical trial NCT06742853: A Study to Investigate the Pharmacokinetics, Safety, Tolerability, and Efficacy of AZD0780 With Ezetimibe Combinations in Healthy Adults With Elevated LDL-C.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Dyslipidemia
Keywords: LDL-C
Hypercholesterolemia
Cholesterol absorption inhibitor
ATP-citrate lyase inhibitor
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-12-19
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Change from baseline in direct Low-density Lipsprotein Cholesterol (LDL-C)
timeFrame: Week 4
measure: Number of participants with adverse events
timeFrame: From screening (Day -56 to -29) to 14 Weeks
Secondary outcomes:
measure: Plasma concentration of AZD0780
timeFrame: From Day 1 to Day 42
measure: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)
timeFrame: From Day 1 to Day 42
measure: Area under concentration-time curve in the dosing interval (AUCtau) (Day 15)
timeFrame: From Day 1 to Day 42
measure: Maximum observed drug concentration (Cmax)
timeFrame: From Day 1 to Day 42
measure: Time to reach maximum observed concentration (tmax)
timeFrame: From Day 1 to Day 42
measure: Change from baseline in LDL-C ultra
timeFrame: Week 4
measure: Change from baseline in LDL-C Friedewald
timeFrame: Week 4
measure: Change from baseline in total cholesterol
timeFrame: Week 4
measure: Change from baseline in non- HDL-C (high-density lipoprotein-cholesterol)
timeFrame: Week 4
measure: Change from baseline in HDL-C
timeFrame: Week 4
measure: Change from baseline in triglycerides
timeFrame: Week 4
measure: Change from baseline in in Lipoprotein A [Lp(a)]
timeFrame: Week 4
measure: Change from baseline in Apolipoprotein B (ApoB)
timeFrame: Week 4
Other outcomes:
Locations:
city: Glendale
country: United States
facility: Research Site
state: California
city: Brooklyn
country: United States
facility: Research Site
state: Maryland
city: Harrow
country: United Kingdom
facility: Research Site
Study officials:
References: