A Study to Investigate Safety, Tolerability, and Pharmacokinetics of AZD3974 in Healthy Participants

A Phase I, Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability and Pharmacokinetics of AZD3974 After Single and Multiple Ascending Dosing to Healthy Participants

The purpose of this study is to assess the safety and tolerability of AZD3974 and characterize the pharmacokinetics (PK) of AZD3974 following oral administration to healthy participants, including participants of Japanese and Chinese descent.

Study Overview

• Status: Recruiting
• Conditions: Healthy Participants
• Intervention / Treatment: Drug: AZD3974; Other: Placebo

Detailed Description

This is a first in human, randomized, single-blind, placebo-controlled study. It consists of two parts.

Part A (single ascending dose - SAD): This study part will enroll six cohorts (plus two optional additional cohorts) of healthy participants (Part A1), three cohorts (plus one optional additional cohort) of healthy Japanese participants (Part A2) and one cohort (plus one optional additional cohort) of healthy Chinese participants (Part A3). Cohort 3 of Part A1 will be extended to evaluate the effect of food intake on the PK of AZD3974. In Part A (all cohorts), participants will receive a single dose of AZD3974 or placebo.

Part B (Multiple Ascending Dose - MAD): This study part will consist of four cohorts (plus two optional additional cohorts) of healthy participants (Part B1) and one cohort (plus one optional additional cohort) of healthy Japanese participants (Part B2). In all Part B cohorts, participants will receive multiple doses of AZD3974 or placebo.

Both Part A and Part B will comprise of:

• A Screening Period of maximum 28 days
• A Dosing session during which participants will receive the study intervention at study specific time points.
• Follow-up Period of 7 days post last-dose.

• Study Type: Interventional
• Enrollment (Estimated): 176
• 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 States
  • California
    • Glendale, California, United States, 91206
      • Recruiting
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21225
      • Recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Healthy male and female (of non-childbearing potential) participants with suitable veins for cannulation or repeated venipuncture at the Screening Visit.
• All females must have a negative pregnancy test. Females of non-childbearing potential must be confirmed via post-menopausal status or documentation of irreversible surgical sterilization at the Screening Visit.
• Sexually active fertile male participants with partners of childbearing potential must adhere to the contraception methods.
• Have a body mass index between 18 and 32 kg/m2 inclusive and weigh at least 50 kg at Screening.
• For healthy Japanese cohorts (Part A2 and Part B2): healthy male and female participants are to be Japanese (eg, natives of Japan or Japan Americans), defined as having both parents and 4 grandparents who are Japanese. This includes second and third generation participants of Japanese descent whose parents or grandparents are living in a country other than Japan.
• For healthy Chinese cohort (Part A3): healthy male and female Chinese participants for whom both parents and 4 grandparents are Chinese. This includes second and third generation participants of Chinese descent whose parents or grandparents are living in a country other than China.

Exclusion Criteria:

• History of any clinically important disease or disorder which, 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.
• Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
• Any abnormal laboratory values, vital signs, or any clinically important abnormalities in clinical chemistry, hematology, or urinalysis results.
• Any positive result on Screening for serum hepatitis B and C viruses and human immunodeficiency virus.
• Any clinically important abnormalities in rhythm, conduction, or morphology of the resting 12 lead electrocardiography at Screening and/or admission to the Clinical Unit .
• Known or suspected history of alcohol or drug abuse or excessive intake of alcohol.
• Positive screen for drugs of abuse, or alcohol, or cotinine.
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity.
• Participants who have previously received AZD3974.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

28

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A1 (SAD) Cohort 1: AZD3974 (Dose 1); Healthy participants will receive a single dose of AZD3974 - Dose 1	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Experimental: Part A1 (SAD) Cohort 2: AZD3974 (Dose 2); Healthy participants will receive a single dose of AZD3974 - Dose 2	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Experimental: Part A1 (SAD) Cohort 3: AZD3974 (Dose 3) (Food Effect Cohort); Healthy participants will receive two single doses of AZD3974 - Dose 3	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Experimental: Part A1 (SAD) Cohort 4: AZD3974 (Dose 4); Healthy participants will receive a single dose of AZD3974 - Dose 4	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Experimental: Part A1 (SAD) Cohort 5: AZD3974 (Dose 5); Healthy participants will receive a single dose of AZD3974 - Dose 5	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Experimental: Part A1 (SAD) Cohort 6: AZD3974 (Dose 6); Healthy participants will receive a single dose of AZD3974 - Dose 6	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Experimental: Part A1 (SAD) optional additional Cohort 7: AZD3974; Healthy participants will receive a single dose of AZD3974	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Experimental: Part A1 (SAD) optional additional Cohort 8: AZD3974; Healthy participants will receive a single dose of AZD3974	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Placebo Comparator: Part A1 (SAD) Cohort: Placebo; Healthy participants will receive a single dose of matching placebo to AZD3974	Other: Placebo; Placebo will be administered as an oral solution.
Placebo Comparator: Part A1 (SAD) Cohort 3: Placebo (Food Effect Cohort); Healthy participants will receive two single doses of matching placebo to AZD3974	Other: Placebo; Placebo will be administered as an oral solution.
Experimental: Part A2 (SAD) Japanese Cohort 1: AZD3974; Healthy Japanese participants will receive a single dose of AZD3974	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Experimental: Part A2 (SAD) Japanese Cohort 2: AZD3974; Healthy Japanese participants will receive a single dose of AZD3974	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Experimental: Part A2 (SAD) Japanese Cohort 3: AZD3974; Healthy Japanese participants will receive a single dose of AZD3974	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Experimental: Part A2 (SAD) optional additional Japanese Cohort 4: AZD3974; Healthy Japanese participants will receive a single dose of AZD3974	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Placebo Comparator: Part A2 (SAD) Japanese Cohort: Placebo; Healthy Japanese participants will receive a single dose of matching placebo to AZD3974	Other: Placebo; Placebo will be administered as an oral solution.
Experimental: Part A3 (SAD) Chinese Cohort 1: AZD3974; Healthy Chinese participants will receive a single dose of AZD3974	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Experimental: Part A3 (SAD) optional additional Chinese Cohort 2: AZD3974; Healthy Chinese participants will receive a single dose of AZD3974	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Placebo Comparator: Part A3 (SAD) Chinese Cohort: Placebo; Healthy Chinese participants will receive a single dose of matching placebo to AZD3974	Other: Placebo; Placebo will be administered as an oral solution.
Experimental: Part B1 (MAD) Cohort 1: AZD3974; Healthy participants will receive multiple doses of AZD3974	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Experimental: Part B1 (MAD) Cohort 2: AZD3974; Healthy participants will receive multiple doses of AZD3974	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Experimental: Part B1 (MAD) Cohort 3: AZD3974; Healthy participants will receive multiple doses of AZD3974	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Experimental: Part B1 (MAD) Cohort 4: AZD3974; Healthy participants will receive multiple doses of AZD3974	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Experimental: Part B1 (MAD) optional additional Cohort 5: AZD3974; Healthy participants will receive multiple doses of AZD3974	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Experimental: Part B1 (MAD) optional additional Cohort 6: AZD3974; Healthy participants will receive multiple doses of AZD3974	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Placebo Comparator: Part Bl (MAD) Cohort: Placebo; Healthy participants will receive multiple doses of matching placebo to AZD3974	Other: Placebo; Placebo will be administered as an oral solution.
Experimental: Part B2 (MAD) Japanese Cohort 1: AZD3974; Healthy Japanese participants will receive multiple doses of AZD397	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Experimental: Part B2 (MAD) optional additional Japanese Cohort 2: AZD3974; Healthy Japanese participants will receive multiple doses of matching placebo to AZD3974	Drug: AZD3974; AZD3974 will be administered as an oral solution.
Placebo Comparator: Part B2 (MAD) Japanese Cohort: Placebo; Healthy Japanese participants will receive multiple doses of matching placebo to AZD3974	Other: Placebo; Placebo will be administered as an oral solution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with adverse events (AEs) and serious adverse events (SAEs)	To assess the safety and tolerability of AZD3974 following oral administration of single and multiple ascending doses in healthy participants, including Chinese and Japanese participants	Part A: Upto Day 7; Part A1 Cohort 3: Upto Day 10; Part B: Upto Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A and Part B: Plasma concentrations of AZD3974	To characterize the plasma concentrations of AZD3974 following single and multiple ascending doses in healthy participants, including Chinese and Japanese participants.	Part A: Day 1 to Day 2; Part B: Day 1 to Day 9
Part A1-Cohort 3: Plasma concentrations of AZD3974	To assess the impact of food (fed) on the single-dose plasma concentrations of AZD3974	Day 1 to Day 4
Part A and Part B: Urine concentrations of AZD3974	To characterize the urine concentration of AZD3974 following single and multiple ascending doses in healthy participants, including Chinese and Japanese participants.	Part A: Day 1; Part B: Day 1 and Day 7
Part A1-Cohort 3: Urine concentrations of AZD3974	To assess the impact of food (fed) on the single-dose urine concentrations of AZD3974	Day 1 and Day 3
Part A and Part B: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)	To characterize the PK of AZD3974 following single and multiple ascending doses in healthy participants, including Chinese and Japanese participants	Part A: Day 1 to Day 2; Part B: Day 1 to Day 9
Part A1-Cohort 3: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)	To assess the impact of food (fed) on the single-dose PK of AZD3974	Day 1 to Day 4
Part A: Area under concentration-time curve from time 0 to infinity (AUCinf)	To characterize the PK of AZD3974 following single ascending doses in healthy participants, including Chinese and Japanese participants	Day 1 to Day 2
Part A1-Cohort 3: Area under concentration-time curve from time 0 to infinity (AUCinf)	To assess the impact of food (fed) on the single-dose PK of AZD3974	Day 1 to Day 4
Part A and Part B: Maximum observed drug concentration (Cmax)	To characterize the PK of AZD3974 following single and multiple ascending doses in healthy participants, including Chinese and Japanese participants	Part A: Day 1 to Day 2; Part B: Day 1 to Day 9
Part A1-Cohort 3: Maximum observed drug concentration (Cmax)	To assess the impact of food (fed) on the single-dose PK of AZD3974	Day 1 to Day 4
Part A and Part B: Time to reach maximum observed concentration (tmax)	To characterize the PK of AZD3974 following single and multiple ascending doses in healthy participants, including Chinese and Japanese participants	Part A: Day 1 to Day 2; Part B: Day 1 to Day 9
Part A1-Cohort 3: Time to reach maximum observed concentration (tmax)	To assess the impact of food (fed) on the single-dose PK of AZD3974	Day 1 to Day 4
Part A and Part B: Terminal elimination half-life (t½λz)	To characterize the PK of AZD3974 following single and multiple ascending doses in healthy participants, including Chinese and Japanese participants	Part A: Day 1 to Day 2; Part B: Day 1 to Day 9
Part A1-Cohort 3: Terminal elimination half-life (t½λz)	To assess the impact of food (fed) on the single-dose PK of AZD3974	Day 1 to Day 4
Part A and Part B: Apparent total body clearance (CL/F)	To characterize the PK of AZD3974 following single and multiple ascending doses in healthy participants, including Chinese and Japanese participants	Part A: Day 1 to Day 2; Part B: Day 1 to Day 9
Part A1-Cohort 3: Apparent total body clearance (CL/F)	To assess the impact of food (fed) on the single-dose PK of AZD3974	Day 1 to Day 4
Part A and Part B: Apparent volume of distribution based on the terminal phase (Vz/F)	To characterize the PK of AZD3974 following single and multiple ascending doses in healthy participants, including Chinese and Japanese participants	Part A: Day 1 to Day 2; Part B: Day 1 to Day 9
Part A1-Cohort 3: Apparent volume of distribution based on the terminal phase (Vz/F)	To assess the impact of food (fed) on the single-dose PK of AZD3974	Day 1 to Day 4
Part A and Part B: Individual and cumulative amount of unchanged drug excreted into urine from time t0 to time tlast [Ae(0-last)]	To characterize the PK of AZD3974 following single and multiple ascending doses in healthy participants, including Chinese and Japanese participants	Part A: Day 1; Part B: Day 1 and Day 7
Part A1-Cohort 3: Individual and cumulative amount of unchanged drug excreted into urine from time t0 to time tlast [Ae(0-last)]	To assess the impact of food (fed) on the single-dose PK of AZD3974	Day 1 and Day 3
Part A and Part B: Individual and cumulative percentage of dose excreted unchanged in urine from time t0 to tlast [fe(0-last)]	To characterize the PK of AZD3974 following single and multiple ascending doses in healthy participants, including Chinese and Japanese participants	Part A: Day 1; Part B: Day 1 and Day 7
Part A1-Cohort 3: Individual and cumulative percentage of dose excreted unchanged in urine from time t0 to tlast [fe(0-last)]	To assess the impact of food (fed) on the single-dose PK of AZD3974	Day 1 and Day 3
Part A and Part B: Renal clearance (CLR)	To characterize the PK of AZD3974 following single and multiple ascending doses in healthy participants, including Chinese and Japanese participants	Part A: Day 1; Part B: Day 1 and Day 7
Part A1-Cohort 3: Renal clearance (CLR)	To assess the impact of food (fed) on the single-dose PK of AZD3974	Day 1 and Day 3
Part A and Part B: Mean Residence Time (MRT)	To characterize the PK of AZD3974 following single and multiple ascending doses in healthy participants, including Chinese and Japanese participants.	Part A: Day 1 to Day 2; Part B: Day 1 to Day 9
Part A1-Cohort 3: Mean Residence Time (MRT)	To assess the impact of food (fed) on the single-dose PK of AZD3974	Day 1 to Day 4
Part A and Part B: Time delay between drug administration and the first observed concentration (tlag)	To characterize the PK of AZD3974 following single and multiple ascending doses in healthy participants, including Chinese and Japanese participants.	Part A: Day 1 to Day 2; Part B: Day 1 to Day 9
Part A1-Cohort 3: Time delay between drug administration and the first observed concentration (tlag)	To assess the impact of food (fed) on the single-dose PK of AZD3974	Day 1 to Day 4
Part A and Part B: Time of last quantifiable concentration (tlast)	To characterize the PK of AZD3974 following single and multiple ascending doses in healthy participants, including Chinese and Japanese participants.	Part A: Day 1 to Day 2; Part B: Day 1 to Day 9
Part A1-Cohort 3: Time of last quantifiable concentration (tlast)	To assess the impact of food (fed) on the single-dose PK of AZD3974	Day 1 to Day 4
Part A and Part B: Individual and cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1 t2)]	To characterize the PK of AZD3974 following single and multiple ascending doses in healthy participants, including Chinese and Japanese participants.	Part A: Day 1; Part B: Day 1 and Day 7
Part A1-Cohort 3: Individual and cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1 t2)]	To assess the impact of food (fed) on the single-dose PK of AZD3974	Day 1 and Day 3
Part A and Part B: Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 - [fe(t1-t2)]	To characterize the PK of AZD3974 following single and multiple ascending doses in healthy participants, including Chinese and Japanese participants.	Part A: Day 1; Part B: Day 1 and Day 7
Part A1-Cohort 3: Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 - [fe(t1-t2)]	To assess the impact of food (fed) on the single-dose PK of AZD3974	Day 1 and Day 3
Part A and Part B: Cumulative amount of unchanged drug excreted into urine (Aeinf)	To characterize the PK of AZD3974 following single and multiple ascending doses in healthy participants, including Chinese and Japanese participants.	Part A: Day 1; Part B : Day 1 and Day 7
Part A1-Cohort 3: Cumulative amount of unchanged drug excreted into urine (Aeinf)	To assess the impact of food (fed) on the single-dose PK of AZD3974	Day 1 and Day 3
Part B: Area under concentration time curve in the dosing interval (AUCtau)	To characterize the PK of AZD3974 following multiple ascending doses in healthy participants, including Japanese participants	Day 1 to Day 9
Part B: Observed lowest concentration before the next dose is administered: (Ctrough)	To characterize the PK of AZD3974 following multiple ascending doses in healthy participants, including Japanese participants.	Day 1 to Day 9
Part B: Accumulation ratio for AUC calculated as steady State AUCτ/First Dose AUCτ (Rac AUC)	To characterize the PK of AZD3974 following multiple ascending doses in healthy participants, including Japanese participants	Day 1 to Day 9
Part B: Accumulation ratio for Cmax calculated as steady State Cmax/First Dose Cmax (Rac Cmax)	To characterize the PK of AZD3974 following multiple ascending doses in healthy participants, including Japanese participants.	Day 1 to Day 9
Part B: Temporal change parameter calculated as steady State AUCτ/First Dose AUCinf (TCP)	To characterize the PK of AZD3974 following multiple ascending doses in healthy participants, including Japanese participants.	Day 1 to Day 9

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2025
• Primary Completion (Estimated): October 21, 2026
• Study Completion (Estimated): October 21, 2026

Study Registration Dates

• First Submitted: December 5, 2025
• First Submitted That Met QC Criteria: December 5, 2025
• First Posted (Actual): December 18, 2025

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Multiple ascending dose; First-in-human; Single ascending dose; Impact of food
• Other Study ID Numbers: D7360C00001

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 shared.

• 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 rerefer 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. 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