A study to investigate the effect of different doses of AZD0780 on low-density lipoprotein cholesterol (LDL-C) levels compared with placebo and its safety and tolerability in participants 18 to 75 years of age with dyslipidemia

Phase 2

Completed

• Conditions: Dyslipidemia Dyslipidemias are alterations to the plasma lipid profile associated often with clinical condition. A common form of dyslipidemia is Hypercholesterolemia due to high level of LDL-cholesterol, which is a major risk factor for Cardiovascular Disease (CVD), such as Ischemic Heart Disease and Ischemic Stroke. CVD is a leading cause of global mortality and a contributor to disability.

• Registration Number: 2023-506197-12-00
• Lead Sponsor: Astrazeneca AB, Astrazeneca AB

Brief Summary

To evaluate the effect of different doses of AZD0780 on low-density lipoprotein cholesterol (LDL-C) versus placebo in “ideal” scenarios in which intercurrent events would not occur.

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-01-16
• Last Update Posted: 2024-04-12

Recruitment & Eligibility

• Status: Ended
• Sex: Not specified
• Target Recruitment: 209

Inclusion Criteria

Males, and females of non-childbearing potential, 18 to 75 years of age, inclusive, at the time of signing the informed consent.

Participants with a fasting low-density lipoprotein cholesterol (LDL-C) ≥ 70 mg/dL (1.8 mmol/L) and ≤ 190 mg/dL (4.9 mmol/L) at screening.

Participants with fasting triglycerides < 400 mg/dL (< 4.52 mmol/L) at screening.

Should be receiving moderate or high-intensity statin therapy for ≥ 2 months prior to screening, according to ACC/AHA guidelines on blood cholesterol management, or to local guidelines, eg, Japanese Atherosclerosis Society guidelines

There should be no planned medication or dose change during study participation.

Body mass index at or above 19.0 kg/m^2.

Exclusion Criteria

Estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m^2 using the Chronic Kidney Disease-Epidemiology Collaboration (CKD-Epi 2021(Age, Sex)) equation at Visit 1.

Uncontrolled hypertension defined as average sitting systolic blood pressure (SBP) > 160 mmHg or diastolic blood pressure (DBP) > 90 mmHg at Visit 1. It is recommended that antihypertensive treatment should be considered/initiated at the principal investigator’s discretion and in accordance with applicable clinical guidelines in order to optimize blood pressure for participants with hypertension during the clinical study.

Heart rate after 10 minutes supine rest < 50 bpm or > 100 bpm at Visit 1

Any laboratory values with the following deviations at Screening Visit 1; test may be repeated at the discretion of the investigator if abnormal: (a) Any positive result on screening for hepatitis B, hepatitis C, or Human Immunodeficiency Virus (HIV). (b) Alanine Aminotransferase/Transaminase (ALT) > 1.5 × Upper Level of Normal (ULN) (c) Aspartate Aminotransferase/Transaminase (AST) > 1.5 × ULN (d) Total Bilirubin (TBL) > ULN (e) Hemoglobin < 12 g/dL in men or < 11 g/dL in women (f) Potassium < LLN

Any clinically important abnormalities in rhythm, conduction or morphology of the resting electrocardiogram (ECG) and any clinically important abnormalities in the 12 lead ECG as judged by the investigator including shortened QTcF< 340ms; family history of long QT syndrome; PR interval shortening < 120 ms; PR interval prolongation >220 ms, intermittent second or third degree AV block or AV dissociation; persistent or intermittent complete bundle branch block, incomplete bundle branch, or interventricular conduction delay with QRS > 110 ms.

Corrected QT Interval (QTcF) > 450 ms; high degree atrioventricular-block grade II-III and sinus node dysfunction with significant sinus pause untreated with pacemaker; and cardiac tachyarrhythmias.

Known or suspected history of drug abuse as judged by the investigator.

History of alcohol abuse or excessive intake of alcohol as judged by the investigator.

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.

History or presence of gastrointestinal, hepatic or renal disease or any other conditions known to interfere with absorption, distribution, metabolism, or excretion of drugs.

Any uncontrolled or serious disease, or any medical (eg, known major active infection or major hematological, renal, metabolic, gastrointestinal, respiratory, or endocrine dysfunction) or surgical condition that, in the opinion of the investigator, may either interfere with participation in the clinical study and/or put the participant at significant risk.

Poorly controlled type 2 diabetes mellitus, defined as hemoglobin A1c (HbA1c) > 10% at Visit 1.

Acute ischemic cardiovascular event in the last 12 months prior to randomization however patients can be included if it is > 6 months from coronary artery bypass graft surgery and > 3 months after percutaneous coronary intervention.

Heart failure with New York Heart Association (NYHA) Class III-IV

Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in-situ, or Stage 1 prostate carcinoma) within the last 10 years.

Recipient of any major organ transplant, e.g., lung, liver, heart, bone marrow, renal.

Low-Density Lipoprotein (LDL) or plasma apheresis within 12 months prior to randomization.

Study & Design

• Study Type: Not specified
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Percent change from baseline of Low-Density Lipoprotein cholesterol (LDL-C) at Week 12		Percent change from baseline of Low-Density Lipoprotein cholesterol (LDL-C) at Week 12

Secondary Outcome Measures

Name	Time	Method
Percent change from baseline at Week 12 in, total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, non-high-density lipoprotein cholesterol (Non-HDL-C), very low-density lipoprotein cholesterol (VLDL-C), apolipoprotein A-1 (ApoA1), apolipoprotein B-100 (ApoB), lipoprotein (a) (Lp(a)), remnant cholesterol, and high-sensitivity C-reactive protein (hsCRP).		Percent change from baseline at Week 12 in, total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, non-high-density lipoprotein cholesterol (Non-HDL-C), very low-density lipoprotein cholesterol (VLDL-C), apolipoprotein A-1 (ApoA1), apolipoprotein B-100 (ApoB), lipoprotein (a) (Lp(a)), remnant cholesterol, and high-sensitivity C-reactive protein (hsCRP).
Safety and tolerability will be assessed in terms of adverse events, vital signs, electrocardiogram (ECG), and clinical laboratory evaluations		Safety and tolerability will be assessed in terms of adverse events, vital signs, electrocardiogram (ECG), and clinical laboratory evaluations
Percent change from baseline of Low-Density Lipoprotein cholesterol (LDL-C) at Week 12		Percent change from baseline of Low-Density Lipoprotein cholesterol (LDL-C) at Week 12
AZD0780 plasma concentrations summarized by sampling timepoint		AZD0780 plasma concentrations summarized by sampling timepoint

Trial Locations

Locations (33)

Arina Trial Research Kft.; 🇭🇺 Oroshaza, Hungary

High Tech Medical Kft.; 🇭🇺 Budapest II, Hungary

University Of Debrecen; 🇭🇺 Debrecen, Hungary

University Of Pecs; 🇭🇺 Pecs, Hungary

Jahn Ferenc Del-Pesti Korhaz Es Rendelointezet; 🇭🇺 Budapest, Hungary

Interna SK s.r.o.; 🇸🇰 Svidnik, Slovakia

Areteus s.r.o.; 🇸🇰 Trebisov, Slovakia

KARDIO 1 s.r.o.; 🇸🇰 Lučenec, Slovakia

MediTask s.r.o.; 🇸🇰 Bratislava, Slovakia

Medispol s.r.o.; 🇸🇰 Presov, Slovakia

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Arina Trial Research Kft.

🇭🇺Oroshaza, Hungary

László Nagy

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