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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astrazeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

7 Feb 2024 → 1 Oct 2024

Decision date (initial)

2024-01-17

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca AB and AstraZeneca K.K. (Japan)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacokinetic, Dose response

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.

Secondary objectives 5

1. To evaluate the effect of different doses of AZD0780 on low-density lipoprotein cholesterol (LDL-C) versus placebo in “real-world” conditions
2. To assess the pharmacokinetics of AZD0780
3. To evaluate the effects of different doses of AZD0780 on other lipid parameters and inflammatory markers versus placebo in “ideal” scenarios in which intercurrent events would not occur
4. To evaluate the effects of different doses of AZD0780 on other lipid parameters and inflammatory markers versus placebo in “real-world” conditions
5. To assess the safety and tolerabiliy of AZD0780

Conditions and MedDRA coding

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.

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Males, and females of non-childbearing potential, 18 to 75 years of age, inclusive, at the time of signing the informed consent.
2. 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.
3. Participants with fasting triglycerides < 400 mg/dL (< 4.52 mmol/L) at screening.
4. 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
5. There should be no planned medication or dose change during study participation.
6. Body mass index at or above 19.0 kg/m^2.

Exclusion criteria 17

1. 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.
2. History or presence of gastrointestinal, hepatic or renal disease or any other conditions known to interfere with absorption, distribution, metabolism, or excretion of drugs.
3. 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.
4. Poorly controlled type 2 diabetes mellitus, defined as hemoglobin A1c (HbA1c) > 10% at Visit 1.
5. 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.
6. Heart failure with New York Heart Association (NYHA) Class III-IV
7. 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.
8. Recipient of any major organ transplant, e.g., lung, liver, heart, bone marrow, renal.
9. Low-Density Lipoprotein (LDL) or plasma apheresis within 12 months prior to randomization.
10. 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.
11. Heart rate after 10 minutes supine rest < 50 bpm or > 100 bpm at Visit 1
12. 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
13. 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.
14. 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.
15. Known or suspected history of drug abuse as judged by the investigator.
16. History of alcohol abuse or excessive intake of alcohol as judged by the investigator.
17. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Percent change from baseline of Low-Density Lipoprotein cholesterol (LDL-C) at Week 12

Secondary endpoints 5

1. Percent change from baseline of Low-Density Lipoprotein cholesterol (LDL-C) at Week 12
2. AZD0780 plasma concentrations summarized by sampling timepoint
3. 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).
4. 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).
5. Safety and tolerability will be assessed in terms of adverse events, vital signs, electrocardiogram (ECG), and clinical laboratory evaluations

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astrazeneca AB

Sponsor organisation

Astrazeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

Astrazeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

Astrazeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

5 EU/EEA countries · 34 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications