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

Study identifier:D7300C00001

ClinicalTrials.gov identifier:NCT06980428

EudraCT identifier:N/A

CTIS identifier:N/A

Recruiting

Official Title

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

Medical condition

Healthy Participants

Phase

Phase 1

Healthy volunteers

Yes

Study drug

AZD4954, Placebo

Sex

All

Estimated Enrollment

120

Study type

Interventional

Age

18 Years - 55 Years

Date

Study Start Date: 27 May 2025

Estimated Primary Completion Date: 04 Dec 2026

Estimated Study Completion Date: 04 Dec 2026

Study design

Allocation: Randomized
Endpoint Classification: -
Intervention Model: Sequential Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Jul 2025 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

Parts A and B:
- 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 Clinical Unit.
- 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.
- Have a body mass index (BMI) between 18 and 35 kg/m2 inclusive.
- For Japanese and Chinese participants (Parts A and B):
a. 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.
b. 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.
Only Part B:
- For Part B (Global MAD Cohorts), at the Screening Visit participants must have elevated Lp(a) ≥ 30 mg/dL.

Exclusion Criteria

Parts A and B:
- 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) 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.

Sort by status

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Arms	Assigned Interventions
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.	Drug: AZD4954 AZD4954 will be administered orally. Drug: Placebo Placebo will be administered orally.
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.	Drug: AZD4954 AZD4954 will be administered orally. Drug: Placebo Placebo will be administered orally.
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.	Drug: AZD4954 AZD4954 will be administered orally. Drug: Placebo Placebo will be administered orally.
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.	Drug: AZD4954 AZD4954 will be administered orally. Drug: Placebo Placebo will be administered orally.
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.	Drug: AZD4954 AZD4954 will be administered orally. Drug: Placebo Placebo will be administered orally.
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.	Drug: AZD4954 AZD4954 will be administered orally. Drug: Placebo Placebo will be administered orally.
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.	Drug: AZD4954 AZD4954 will be administered orally. Drug: Placebo Placebo will be administered orally.
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.	Drug: AZD4954 AZD4954 will be administered orally. Drug: Placebo Placebo will be administered orally.
Experimental: Part A1: SAD Optional Cohort 3 (Japanese) - AZD4954 This additional cohort may be added depending on the findings.	Drug: AZD4954 AZD4954 will be administered orally. Drug: Placebo Placebo will be administered orally.
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.	Drug: AZD4954 AZD4954 will be administered orally. Drug: Placebo Placebo will be administered orally.
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.	Drug: AZD4954 AZD4954 will be administered orally. Drug: Placebo Placebo will be administered orally.
Experimental: Part B: Global MAD Cohort 1 - AZD4954 (Dose 1) Participants will receive multiple doses of AZD4954 (Dose 1) or matching placebo for 21 days.	Drug: AZD4954 AZD4954 will be administered orally. Drug: Placebo Placebo will be administered orally.
Experimental: Part B: Global MAD Cohort 2 - AZD4954 (Dose 2) Participants will receive multiple doses of AZD4954 (Dose 2) or matching placebo for 21 days.	Drug: AZD4954 AZD4954 will be administered orally. Drug: Placebo Placebo will be administered orally.
Experimental: Part B: Global MAD Cohort 3 - AZD4954 (Dose 3) Participants will receive multiple doses of AZD4954 (Dose 3) or matching placebo for 21 days.	Drug: AZD4954 AZD4954 will be administered orally. Drug: Placebo Placebo will be administered orally.
Experimental: Part B: Optional Global MAD Cohort 4 - AZD4954 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 AZD4954 will be administered orally. Drug: Placebo Placebo will be administered orally.
Experimental: Part B: MAD Cohort (Japanese) - AZD4954 (Dose 3) Japanese participants will receive multiple doses of AZD4954 (Dose 3) or matching placebo for 14 days.	Drug: AZD4954 AZD4954 will be administered orally. Drug: Placebo Placebo will be administered orally.

Documents available

Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]