RecruitingPhase 1NCT06980428

A Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD4954 in Healthy Adult Participants With or Without Elevated Lipoprotein (a) (Lp[a]) Levels, and Participants With Dyslipidemia

A Phase I, Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AZD4954 Following Single and Multiple Ascending Dose Administration to Healthy Participants With or Without Elevated Lp(a) Levels, and Participants With Dyslipidemia

Sponsor

AstraZeneca

Enrollment

136 participants

Start Date

May 27, 2025

Study Type

INTERVENTIONAL

Conditions

Healthy Participants Dyslipidemia

Summary

The purpose of the study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single and multiple ascending doses of AZD4954 in healthy participants with or without elevated Lipoprotein(a) (Lp\[a\]) levels and participants with dyslipidemia.

Eligibility

Min Age: 18 YearsMax Age: 70 Years

Inclusion Criteria22

All Parts:
Participants with plasminogen level (concentration) within normal range at the Screening Visit.
All females must have a negative pregnancy test at the Screening Visit and on admission to the study site.
Females of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception.
Females of non-childbearing potential must be confirmed at the Screening Visit.
Sexually active fertile male participants with partners of childbearing potential must adhere to the study specific contraception methods from the time of first administration of study intervention until 3 months after the study Follow-up Visit.
Parts A and B (Healthy Participants):
Male and female participants aged 18 to 65 years with suitable veins for cannulation or repeated venipuncture.
Have a body mass index (BMI) between 18 and 35 kg/m² inclusive.
For Japanese and Chinese participants (Parts A and B):
A Japanese participant is defined as having both parents and 4 grandparents who are ethnically Japanese. This includes second and third generation Japanese whose parents or grandparents are living in a country other than Japan.
A Chinese participant is defined as having both parents and 4 grandparents who are ethnically Chinese. This includes second and third generation Chinese whose parents or grandparents are living in a country other than China.
Part B (Healthy Participants):
Participants must have elevated Lp(a) ≥ 30 mg/dL at the Screening Visit.
Part B (Participants with Dyslipidemia):
Male and female participants aged 18 to 70 years with suitable veins for cannulation or repeated venipuncture.
Have a BMI \> 18 kg/m².
Participants must have elevated Lp(a) ≥ 70 mg/dL at the Screening Visit.
Participants with a fasting LDL-C ≥ 70 mg/dL and \< 190 mg/L at the Screening Visit.
Participants should be receiving moderate or high-intensity statin therapy for ≥ 2 months prior to the Screening Visit, according to the American College of Cardiology/American Heart Association guidelines on blood cholesterol management.
Participants with documented coronary artery disease, stroke, or peripheral artery disease or at moderate or high risk for an atherosclerotic cardiovascular disease event.
There should be no planned medication or dose change during study participation.

Exclusion Criteria19

All Parts:
History of any clinically important disease or disorder.
History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
Participants with known bleeding or coagulation disorders.
Participants who have an elevated high-sensitivity C-reactive protein (\> 3 mg/L) or have a prothrombin time/international normalized ratio (PT/INR) or activated partial thromboplastin time (aPTT) \> 1.25 times × upper limit normal (ULN).
Any clinically important abnormalities in hematology, coagulation, clinical chemistry, urinalysis, abnormal vital signs or abnormal laboratory values.
Any positive result on Screening for serum hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C virus (HCV) or human immunodeficiency virus (HIV).
Any clinically important abnormalities in rhythm, conduction, or morphology of the resting 12-lead electrocardiogram (ECG) at Screening.
Use of drugs with enzyme inducing properties such as St John's Wort within 3 weeks prior to the first administration of study intervention.
Parts A and B (Healthy Participants):
Use of any prescribed or nonprescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, intake of \> 3 × daily recommended levels of vitamins and minerals during the 2 weeks prior to the first administration of study intervention or longer if the medication has a long half-life.
Current smokers or those who have smoked or used nicotine products.
Part B (Participants with Dyslipidemia):
Acute ischemic cardiovascular event in the last 12 months prior to randomization.
Poorly controlled diabetes.
Previous administration of Lp(a) inhibitor.
Have uncontrolled hypertension.
Abnormal vital heart rate.