Recruiting
Phase 1

AZD4954

Sponsor:

AstraZeneca

Code:

NCT06980428

Conditions

Healthy Participants

Dyslipidemia

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Interventions

AZD4954

Placebo

Study Details

Brief 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.

Conditions

Healthy Participants

Dyslipidemia

Study ID

NCT06980428

Start date

May 27, 2025

Status verified date

Aug, 2026

Completion date

Apr 9, 2027

Anticipated

Primary completion date

Apr 9, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Not accepted

Inclusion Criteria:

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):

1. 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.
2. 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 Criteria:

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.

Study Design

Enrollment

136 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part A1: SAD Cohort 1 - AZD4954 (Dose 1)

Participants will receive a single dose of AZD4954 (Dose 1) or matching placebo on Day 1.

experimental: Part A1: SAD Cohort 2 - AZD4954 (Dose 2)

Participants will receive a single dose of AZD4954 (Dose 2) or matching placebo on Day 1.

experimental: Part A1: SAD Cohort 3 - AZD4954 (Dose 3)

Participants will receive a single dose of AZD4954 (Dose 3) or matching placebo on Day 1.

experimental: Part A1: SAD Cohort 4 - AZD4954 (Dose 4)

Participants will receive a single dose of AZD4954 (Dose 4) or matching placebo on Day 1.

experimental: Part A1: SAD Cohort 5 - AZD4954 (Dose 5)

Participants will receive a single dose of AZD4954 (Dose 5) or matching placebo on Day 1.

experimental: Part A1: SAD Optional Cohort 6 - AZD4954 (Dose 6)

Participants will receive a single dose of AZD4954 (Dose 6) or matching placebo on Day 1. This additional cohort may be added depending on the findings.

experimental: Part A1: SAD Cohort 1 (Japanese) - AZD4954 (Dose 2)

Japanese participants will receive a single dose of AZD4954 (Dose 2) or matching placebo on Day 1.

experimental: Part A1: SAD Cohort 2 (Japanese) - AZD4954 (Dose 3)

Japanese participants will receive a single dose of AZD4954 (Dose 3) or matching placebo on Day 1.

experimental: Part A1: SAD Optional Cohort 3 (Japanese) - AZD4954

This additional cohort may be added depending on the findings.

experimental: Part A1: SAD Cohort 1 (Chinese) - AZD4954 (Dose 5)

Chinese participants will receive a single dose of AZD4954 (Dose 5) or matching placebo at the highest dose level on Day 1.

experimental: Part A2: SAD Food Effect Cohort - AZD4954 (Dose 2)

Participants will receive a single dose of AZD4954 (Dose 2) or matching placebo with a high-calorie, high-fat breakfast on Day 1.

experimental: Part A2: SAD Food Effect Cohort - AZD4954 (Dose 3)

Participants will receive a single dose of AZD4954 (Dose 3) or matching placebo with a high-calorie, high-fat breakfast on Day 1.

experimental: Part B: Global MAD Cohort 1 (healthy participants) - AZD4954 (Dose 1)

Participants will receive multiple doses of AZD4954 (Dose 1) or matching placebo for 21 days.

experimental: Part B: Global MAD Cohort 2 (healthy participants) - AZD4954 (Dose 2)

Participants will receive multiple doses of AZD4954 (Dose 2) or matching placebo for 21 days.

experimental: Part B: Global MAD Cohort 3 (healthy participants) - AZD4954 (Dose 3)

Participants will receive multiple doses of AZD4954 (Dose 3) or matching placebo for 21 days.

experimental: Part B: Optional Global MAD Cohort 4 (healthy participants) - AZD4954

Participants will receive multiple doses of AZD4954 or matching placebo for 21 days. This additional cohort may be added depending on the findings.

experimental: Part B: MAD Cohort (Japanese) - AZD4954 (Dose 3)

Japanese participants will receive multiple doses of AZD4954 (Dose 3) or matching placebo for 21 days.

experimental: Part B: Global MAD Cohort (participants with dyslipidemia) - AZD4954 (Dose 1)

Participants with dyslipidemia will receive multiple doses of AZD4954 (Dose 1) or matching placebo for 21 days.

Interventions

AZD4954

AZD4954 will be administered orally.

Placebo

Placebo will be administered orally.

Primary outcome measure

  • Part A: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: From Screening (Day -28 to Day -2) to Follow-up visit (Up to Day 29±2 days) ]
  • Part B: Number of participants with AEs and SAEs [ Time Frame: From Screening (Day -28 to Day -2) to Follow-up visit (Up to Day 49±2 days) ]

Central Contacts and Locations

Central contacts

AstraZeneca Clinical Study Information Center

1-877-240-9479information.center@astrazeneca.com

Locations

Research Site

Recruiting

Glendale, California, United States, 91206

Research Site

Recruiting

Inverness, Florida, United States, 34452

Research Site

Recruiting

Jacksonville, Florida, United States, 32216

Research Site

Recruiting

Port Orange, Florida, United States, 32127

Research Site

Recruiting

Brooklyn, Maryland, United States, 21225

Research Site

Recruiting

San Antonio, Texas, United States, 78229

More Information

Sponsor

AstraZeneca

Last update posted

Aug 24, 2026

Last verified

Aug, 2026

Keywords

  • Lipoprotein(a)
  • Low-density lipoprotein cholesterol (LDL-C)

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by AstraZeneca on 2026-08-24.