A Study to Investigate the Safety and Pharmacokinetics of Single- and Multiple-ascending Doses of AZD4916 in Healthy Volunteers

A Phase I, Randomized, Single-blind, Placebo-controlled, 2-Part Study to Assess the Safety, Tolerability, and Pharmacokinetics of AZD4916 Following Single- and Multiple-ascending-dose Administration to Healthy Adult Volunteers (Including Japanese and Chinese Healthy Volunteers)

The main purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK) of AZD4916 in healthy adult participants.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: AZD4916; Other: Placebo

Detailed Description

This is a single-blind, placebo-controlled study conducted at a single clinical unit.

The study will comprise of:

• Part 1: Single ascending dose (SAD) part (part 1a) and a Multiple ascending dose (MAD) part (part 1b), both in global participants.
• Part 2: SAD part (part 2a) and a MAD part (part 2b) specifically for Japanese and Chinese participants only.

• Study Type: Interventional
• Enrollment (Estimated): 178
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• United Kingdom
  • Harrow, United Kingdom, HA1 3UJ
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Main Inclusion Criteria:

• Healthy male and female participants with suitable veins for cannulation or repeated venipuncture.
• All females must have negative pregnancy test and females of childbearing potential must not be lactating and must agree to use an approved method of highly effective contraception.
• Have a Body Mass Index between 18 and 30 kg/m2 inclusive and weigh at least 45 kg at Screening.
• Part 2, Japanese participants only: Japanese participants must have been born in Japan, have 2 Japanese biological parents and 4 Japanese grandparents (as confirmed by the interview), and must not have lived outside of Japan for more than 10 years at the time of the Screening Visit.
• Part 2, Chinese participants only: Chinese participants must have been born in China (including Hong Kong, Macau, and Taiwan), have 2 Chinese biological parents and 4 Chinese grandparents (as confirmed by the interview), and must not have lived outside of China for more than 10 years at the time of the Screening Visit.

Main Exclusion Criteria:

• History of any clinically important disease or disorder which, in the opinion of the Principal Investigator, may either put the participant at risk because of participation in the study, or influence the results or the participant's ability to participate in the study.
• History or presence of gastrointestinal, hepatic, or renal disease or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• History of chest irradiation, fibrosis, malignancy, surgical procedure, trauma or liver disease.
• Any clinically important abnormalities in clinical chemistry, hematology, or urinalysis results.
• Evidence of active tuberculosis or Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV) or Hepatitis C virus (HCV) infection.
• Abnormal vital signs or clinically important abnormalities in rhythm.
• Current smokers, known or suspected history of alcohol, drug abuse or caffeine intake.
• History of severe allergy/hypersensitivity.
• Plasma donation within 1 month of the Screening Visit or any blood donation/blood loss > 500 mL during the 3 months prior to the Screening Visit.
• Participants who are vegans or have dietary restrictions.
• Vulnerable participants, e.g., kept in detention, protected adults under guardianship, trusteeship, or committed to an institution by governmental or juridical order.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZD4916; Parts 1a and 2a participants will receive a single oral dose of AZD4916 on Day 1. Parts 1b and 2b participants will receive a single oral dose of AZD4916 on Day 1 and multiple doses of AZD4916 on Days 4 through 17.	Drug: AZD4916; AZD4916 will be administered as oral solution.
Placebo Comparator: Placebo; Parts 1a and 2a participants will receive a single oral dose of placebo on Day 1. Parts 1b and 2b participants will receive a single dose placebo on Day 1 and multiple doses of placebo on Days 4 through 17.	Other: Placebo; Placebo will be administered as oral solution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs)	The safety and tolerability of AZD4916 following oral administration of single-ascending doses and multiple-ascending doses to healthy participants (including Japanese and Chinese) will be assessed.	From Screening (Day -29 to Day -2) up to 44 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under concentration-time curve from time zero to infinity (AUCinf)	The single-dose and steady-state PK of AZD4916 following oral administration of single-ascending doses and multiple-ascending doses of AZD4916 to healthy volunteers (including Japanese and Chinese healthy volunteers) will be characterised.	Part 1a and 2a: Up to Day 8, Part 1b and 2b: Up to Day 24
Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)	The single-dose and steady-state PK of AZD4916 following oral administration of single-ascending doses and multiple-ascending doses of AZD4916 to healthy volunteers (including Japanese and Chinese healthy volunteers) will be characterised.	Part 1a and 2a: Up to Day 8, Part 1b and 2b: Up to Day 24
Area under concentration-time curve in the dosing interval (AUCtau)	The single-dose and steady-state PK of AZD4916 following oral administration of single-ascending doses and multiple-ascending doses of AZD4916 to healthy volunteers (including Japanese and Chinese healthy volunteers) will be characterised.	Part 1a and 2a: Up to Day 8, Part 1b and 2b: Up to Day 24
Maximum observed drug concentration (Cmax)	The single-dose and steady-state PK of AZD4916 following oral administration of single-ascending doses and multiple-ascending doses of AZD4916 to healthy volunteers (including Japanese and Chinese healthy volunteers) will be characterised.	Part 1a and 2a: Up to Day 8, Part 1b and 2b: Up to Day 24

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Estimated): June 27, 2025
• Primary Completion (Estimated): September 24, 2026
• Study Completion (Estimated): September 24, 2026

Study Registration Dates

• First Submitted: April 23, 2025
• First Submitted That Met QC Criteria: April 23, 2025
• First Posted (Actual): April 30, 2025

Study Record Updates

• Last Update Posted (Actual): April 30, 2025
• Last Update Submitted That Met QC Criteria: April 23, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Multiple-ascending dose; Single-ascending dose
• Other Study ID Numbers: D7340C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure."Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
• IPD Sharing 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 refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing 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. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No