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

NCT06980428 | Recruiting Phase 1 FDA Drug

• 1 other identifier: D7300C00001
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 6

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Part A: Number of participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

  To assess the safety and tolerability of AZD4954 following oral administration of SAD (Part A).

  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

  To assess the safety and tolerability of AZD4954 following oral administration of MAD (Part B).

  From Screening (Day -28 to Day -2) to Follow-up visit (Up to Day 49±2 days)

Secondary Outcomes (21)

• Part A: Area under concentration-time curve from time 0 to infinity (AUCinf)

  Up to Day 29±2 days

• Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)

  Part A: Up to Day 29±2 days; Part B: Up to Day 49±2 days

• Part B: Area under concentration-time curve in the dosing interval (AUCtau)

  Up to Day 49±2 days

• Dose normalized AUClast (AUClast/D)

  Part A: Up to Day 29±2 days; Part B: Up to Day 49±2 days

• Dose normalized AUCinf (AUCinf/D)

  Part A: Up to Day 29±2 days; Part B: Up to Day 49±2 days

Study Arms (18)

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

EXPERIMENTAL

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

Drug: AZD4954; Drug: Placebo

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

EXPERIMENTAL

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

Drug: AZD4954; Drug: Placebo

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

EXPERIMENTAL

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

Drug: AZD4954; Drug: Placebo

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

EXPERIMENTAL

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

Drug: AZD4954; Drug: Placebo

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

EXPERIMENTAL

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

Drug: AZD4954; Drug: Placebo

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

EXPERIMENTAL

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.

Drug: AZD4954; Drug: Placebo

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

EXPERIMENTAL

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

Drug: AZD4954; Drug: Placebo

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

EXPERIMENTAL

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

Drug: AZD4954; Drug: Placebo

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

EXPERIMENTAL

This additional cohort may be added depending on the findings.

Drug: AZD4954; Drug: Placebo

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

EXPERIMENTAL

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

Drug: AZD4954; Drug: Placebo

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

EXPERIMENTAL

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

Drug: AZD4954; Drug: Placebo

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

EXPERIMENTAL

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

Drug: AZD4954; Drug: Placebo

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

EXPERIMENTAL

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

Drug: AZD4954; Drug: Placebo

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

EXPERIMENTAL

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

Drug: AZD4954; Drug: Placebo

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

EXPERIMENTAL

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

Drug: AZD4954; Drug: Placebo

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

EXPERIMENTAL

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

Drug: AZD4954; Drug: Placebo

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

EXPERIMENTAL

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

Drug: AZD4954; Drug: Placebo

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

EXPERIMENTAL

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

Drug: AZD4954; Drug: Placebo

Interventions

AZD4954 DRUG

AZD4954 will be administered orally.

Part A1: SAD Cohort 1 (Chinese) - AZD4954 (Dose 5); Part A1: SAD Cohort 1 (Japanese) - AZD4954 (Dose 2); Part A1: SAD Cohort 1 - AZD4954 (Dose 1); Part A1: SAD Cohort 2 (Japanese) - AZD4954 (Dose 3); Part A1: SAD Cohort 2 - AZD4954 (Dose 2); Part A1: SAD Cohort 3 - AZD4954 (Dose 3); Part A1: SAD Cohort 4 - AZD4954 (Dose 4); Part A1: SAD Cohort 5 - AZD4954 (Dose 5); Part A1: SAD Optional Cohort 3 (Japanese) - AZD4954; Part A1: SAD Optional Cohort 6 - AZD4954 (Dose 6); Part A2: SAD Food Effect Cohort - AZD4954 (Dose 2); Part A2: SAD Food Effect Cohort - AZD4954 (Dose 3); Part B: Global MAD Cohort (participants with dyslipidemia) - AZD4954 (Dose 1); Part B: Global MAD Cohort 1 (healthy participants) - AZD4954 (Dose 1); Part B: Global MAD Cohort 2 (healthy participants) - AZD4954 (Dose 2); Part B: Global MAD Cohort 3 (healthy participants) - AZD4954 (Dose 3); Part B: MAD Cohort (Japanese) - AZD4954 (Dose 3); Part B: Optional Global MAD Cohort 4 (healthy participants) - AZD4954

Placebo DRUG

Placebo will be administered orally.

Part A1: SAD Cohort 1 (Chinese) - AZD4954 (Dose 5); Part A1: SAD Cohort 1 (Japanese) - AZD4954 (Dose 2); Part A1: SAD Cohort 1 - AZD4954 (Dose 1); Part A1: SAD Cohort 2 (Japanese) - AZD4954 (Dose 3); Part A1: SAD Cohort 2 - AZD4954 (Dose 2); Part A1: SAD Cohort 3 - AZD4954 (Dose 3); Part A1: SAD Cohort 4 - AZD4954 (Dose 4); Part A1: SAD Cohort 5 - AZD4954 (Dose 5); Part A1: SAD Optional Cohort 3 (Japanese) - AZD4954; Part A1: SAD Optional Cohort 6 - AZD4954 (Dose 6); Part A2: SAD Food Effect Cohort - AZD4954 (Dose 2); Part A2: SAD Food Effect Cohort - AZD4954 (Dose 3); Part B: Global MAD Cohort (participants with dyslipidemia) - AZD4954 (Dose 1); Part B: Global MAD Cohort 1 (healthy participants) - AZD4954 (Dose 1); Part B: Global MAD Cohort 2 (healthy participants) - AZD4954 (Dose 2); Part B: Global MAD Cohort 3 (healthy participants) - AZD4954 (Dose 3); Part B: MAD Cohort (Japanese) - AZD4954 (Dose 3); Part B: Optional Global MAD Cohort 4 (healthy participants) - AZD4954

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (6)

Research Site

Glendale, California, 91206, United States

RECRUITING

Research Site

Inverness, Florida, 34452, United States

RECRUITING

Research Site

Jacksonville, Florida, 32216, United States

RECRUITING

Research Site

Port Orange, Florida, 32127, United States

NOT YET RECRUITING

Research Site

Brooklyn, Maryland, 21225, United States

RECRUITING

Research Site

San Antonio, Texas, 78229, United States

RECRUITING

MeSH Terms

Conditions

Dyslipidemias

Condition Hierarchy (Ancestors)

Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2025
• First Posted: May 20, 2025
• Study Start: May 27, 2025
• Primary Completion (Estimated): December 4, 2026
• Study Completion (Estimated): December 4, 2026
• Last Updated: May 1, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

US (6)