A Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, and Pharmacokinetics of AZD8965 in Healthy Participants (Including Japanese and Chinese Participants) and an Open-label Cohort to Assess the Effect of Food on the Pharmacokinetics of AZD8965 in Healthy Participants

A Phase I Randomized, Single-blind, Placebo-controlled Study to Assess the Safety, Tolerability, and Pharmacokinetics of AZD8965 Following Single and Multiple Ascending Dose Administration to Healthy Participants (Including Japanese and Chinese Participants) and an Open-label Cohort to Assess the Effect of Food on the Pharmacokinetics of AZD8965 in Healthy Participants

The purpose of this study is to assess the safety, tolerability, and pharmacokinetics (PK) of AZD8965 via single and multiple ascending doses in healthy participants (including Japanese and Chinese participants), and to assess the effect of food on the safety, tolerability, and PK of orally administered AZD8965.

Study Overview

• Status: Completed
• Conditions: Healthy Participants
• Intervention / Treatment: Other: Placebo; Drug: AZD8965

Detailed Description

This is a first in human single and multiple ascending dose study. The study consists of 4 parts: Part 1 (single ascending dose [SAD]), Part 2 (multiple ascending dose [MAD]), Part 3A (Japanese and Chinese SAD), Part 3B (Japanese and Chinese combined SAD and MAD), and Part 4 (Food Effect).

Each study part includes a 28-day screening period and a residential period during which participants will be resident at the Clinical Unit from the day before study intervention administration (Day -1) until at least 48-72 hours after the study intervention administration.

• Study Type: Interventional
• Enrollment (Actual): 147
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Glendale, California, United States, 91206
      • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Healthy male and female participants (including Japanese and Chinese participants) with suitable veins for cannulation or repeated venipuncture.
• All females of childbearing potential must have a negative pregnancy test at the Screening Visit (serum) and on admission (urine) to the Clinical Unit.
• All females of childbearing potential must not be lactating and if heterosexually active must agree to use an approved method of highly effective contraception with low user dependency and their non-sterilized male partners must use a condom, to avoid pregnancy from the time of first administration of study intervention until 20 days after the last dose of study intervention. Females must not use hormonal contraceptives or hormone replacement therapy during the study.

• Females of non-childbearing potential must be confirmed at the Screening Visit by fulfilling one of the following criteria:

  1. Postmenopausal defined as amenorrhea for at least 12 months following cessation of all exogenous hormonal treatments and without an alternative medical cause and the follicle stimulating hormone (FSH) level is in the postmenopausal range.
  2. Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy. Tubal ligation is not acceptable.
• Sexually active fertile male participants with partners of childbearing potential must adhere to the specified contraception methods from the time of first administration of study intervention administration until 20 days after the last dose of study intervention.
• Have a body mass index (BMI) between 18 and 30 kilogram (kg)/square meter (m2) inclusive and weigh at least 45 kg.

Part 3A and Part 3B (Japanese Participants)

• Healthy Japanese participants are eligible based on meeting all of the following:

  1. Born in Japan
  2. Have 2 Japanese biological parents and 4 Japanese grandparents.
  3. Did not live outside Japan for more than 10 years at the time of Screening. Part 3A and Part 3B (Chinese Participants)

• Healthy Chinese participants. Participants of Chinese ancestry are eligible based on meeting all of the following:

  1. Born in mainland China, Hong Kong, Macau, or Taiwan
  2. Have 2 Chinese biological parents and 4 Chinese grandparents as confirmed by the interview.
  3. Did not live outside China for more than 10 years at the time of Screening.

Exclusion Criteria:

• History of any clinically important disease or disorder which may either put the participant at risk or influence the results or the participant's ability to participate in the study.
• Chronic or ongoing gastrointestinal, respiratory, hepatic, renal disease, pancreatic disease, diabetes mellitus, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
• Chronic or ongoing neurological disorder, any clinically important past or ongoing psychiatric disorder which may confound assessment of the potential neurologic effects of this product.
• Participants with a history of hypertension or cardiovascular disease.
• Any clinically important illness, medical/surgical procedure, or trauma within 4 weeks of the first administration of study intervention.
• Participant with chronic infections (e.g., urinary tract infection) or who are at increased risk of infection (e.g., surgery, trauma, severe dental disease, or significant infection).
• Participants with a known or suspected defect in the function of the urea cycle, or with family history of a urea cycle disorder in one or more biological relative.
• Any abnormal laboratory values and vital signs.
• Ongoing acquired or inherited immunodeficiency disorders, including but not limited to human immunodeficiency virus (HIV) or common variable immunodeficiency, or the participant is taking immune replacement therapy.
• History of severe allergy/hypersensitivity or ongoing clinically important allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to AZD8965.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

14

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: SAD Cohort 1 - AZD8965 (Dose 1); Participants will receive a single dose of AZD8965 (Dose 1) or matching placebo to AZD8965 on Day 1.	Other: Placebo; Placebo will be administered orally.; Drug: AZD8965; AZD8965 will be administered orally.
Experimental: Part 1: SAD Cohort 2 - AZD8965 (Dose 2); Participants will receive a single dose of AZD8965 (Dose 2) or matching placebo to AZD8965 on Day 1.	Other: Placebo; Placebo will be administered orally.; Drug: AZD8965; AZD8965 will be administered orally.
Experimental: Part 1: SAD Cohort 3 - AZD8965 (Dose 3); Participants will receive a single dose of AZD8965 (Dose 3) or matching placebo to AZD8965 on Day 1.	Other: Placebo; Placebo will be administered orally.; Drug: AZD8965; AZD8965 will be administered orally.
Experimental: Part 1: SAD Cohort 4 - AZD8965 (Dose 4); Participants will receive a single dose of AZD8965 (Dose 4) or matching placebo to AZD8965 on Day 1.	Other: Placebo; Placebo will be administered orally.; Drug: AZD8965; AZD8965 will be administered orally.
Experimental: Part 1: SAD Cohort 5 - AZD8965 (Dose 5); Participants will receive a single dose of AZD8965 (Dose 5) or matching placebo to AZD8965 on Day 1.	Other: Placebo; Placebo will be administered orally.; Drug: AZD8965; AZD8965 will be administered orally.
Experimental: Part 2: MAD Cohort 1 - AZD8965 (Dose 1); Participants will receive multiple doses of AZD8965 (Dose 1) or matching placebo to AZD8965 from Day 1 to Day 8.	Other: Placebo; Placebo will be administered orally.; Drug: AZD8965; AZD8965 will be administered orally.
Experimental: Part 2: MAD Cohort 2 - AZD8965 (Dose 2); Participants will receive multiple doses of AZD8965 (Dose 2) or matching placebo to AZD8965 from Day 1 to Day 8.	Other: Placebo; Placebo will be administered orally.; Drug: AZD8965; AZD8965 will be administered orally.
Experimental: Part 2: MAD Cohort 3 - AZD8965 (Dose 3); Participants will receive multiple doses of AZD8965 (Dose 3) or matching placebo to AZD8965 from Day 1 to Day 8.	Other: Placebo; Placebo will be administered orally.; Drug: AZD8965; AZD8965 will be administered orally.
Experimental: Part 3A: SAD Cohort 1 (Japanese) - AZD8965 (Dose 1); Japanese participants will receive a single dose of AZD8965 (Dose 1) or matching placebo to AZD8965 on Day 1.	Other: Placebo; Placebo will be administered orally.; Drug: AZD8965; AZD8965 will be administered orally.
Experimental: Part 3A: SAD Cohort 2 (Japanese) - AZD8965 (Dose 2); Japanese participants will receive a single dose of AZD8965 (Dose 2) or matching placebo to AZD8965 on Day 1.	Other: Placebo; Placebo will be administered orally.; Drug: AZD8965; AZD8965 will be administered orally.
Experimental: Part 3A: SAD Cohort 3 (Chinese) - AZD8965 (Dose 1); Chinese participants will receive a single dose of AZD8965 (Dose 1) or matching placebo to AZD8965 on Day 1.	Other: Placebo; Placebo will be administered orally.; Drug: AZD8965; AZD8965 will be administered orally.
Experimental: Part 3B: Single and multiple ascending dose (SMAD) Cohort 1 (Japanese) - AZD8965 (Dose 1); Japanese participants will receive a single dose of AZD8965 (Dose 1) or matching placebo to AZD8965 on Day 1, followed by multiple doses of AZD8965 or matching placebo from Day 3 until Day 9.	Other: Placebo; Placebo will be administered orally.; Drug: AZD8965; AZD8965 will be administered orally.
Experimental: Part 3B: SMAD Cohort 2 (Chinese) - AZD8965 (Dose 1); Chinese participants will receive a single dose of AZD8965 (Dose 1) or matching placebo to AZD8965 on Day 1, followed by multiple doses of AZD8965 or matching placebo from Day 3 until Day 9.	Other: Placebo; Placebo will be administered orally.; Drug: AZD8965; AZD8965 will be administered orally.
Experimental: Part 4: Food Effect Cohort - AZD8965; Participants will receive 2 single dose treatments of AZD8965 [following an overnight fast of at least 10 hours in a fasted state or a fed state (after a high fat meal)].	Drug: AZD8965; AZD8965 will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts 1 and 3A: Number of participants with adverse events (AEs) and serious adverse events (SAEs)	To assess the safety and tolerability of AZD8965 following oral administration of single ascending doses to healthy participants.	SAEs: From Screening (Day -28) to 5 weeks; AEs: From Day 1 to 5 weeks
Parts 2 and 3B: Number of participants with AEs and SAEs	To assess the safety and tolerability of AZD8965 following oral administration of multiple ascending doses to healthy participants.	SAEs: From Screening (Day -28) to 8 weeks; AEs: From Day 1 to 8 weeks.
Part 4: Maximum observed drug concentration (Cmax)	To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 7 (72-hour post dose)
Part 4: Area under concentration-time curve from time 0 to infinity (AUCinf)	To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 7 (72-hour post dose)
Part 4: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)	To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 7 (72-hour post dose)
Part 4: Time to reach maximum observed concentration (tmax)	To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 7 (72-hour post dose)
Part 4: Partial area under the concentration-time curve from time t1 to time t2 [AUC(t1-t2)]	To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 7 (72-hour post dose)
Part 4: Terminal elimination half-life (t½λz)	To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 7 (72-hour post dose)
Part 4: Mean Residence Time (MRTinf)	To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 7 (72-hour post dose)
Part 4: Apparent total body clearance (CL/F)	To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 7 (72-hour post dose)
Part 4: Apparent volume of distribution based on the terminal (Vz/F)	To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 7 (72-hour post dose)
Part 4: Accumulation ratio for AUC (Rac AUC)	To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 7 (72-hour post dose)
Part 4: Accumulation ratio for Cmax (Rac Cmax)	To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 7 (72-hour post dose)
Part 4: Individual and cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)]	To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 5
Part 4: Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 [fe(t1-t2)]	To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 5
Part 4: Relative bioavailability calculated as test AUC/reference AUC (Frel AUC)	To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 7 (72-hour post dose)
Part 4: Relative bioavailability calculated as test Cmax/reference Cmax (Frel Cmax)	To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 7 (72-hour post dose)
Part 4: Renal clearance (CLR)	To assess the effect of a high fat meal compared to fasting conditions on the PK of active drug and pro-drug following oral administration of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 5

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parts 1, 2, 3A and 3B: Maximum observed drug concentration (Cmax)	To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants.	Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose)
Parts 1, 2, 3A and 3B: Area under concentration-time curve from time 0 to infinity (AUCinf)	To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants.	Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose)
Parts 1, 2, 3A and 3B: Area under concentration-curve from time 0 to the last quantifiable concentration (AUClast)	To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants.	Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose)
Parts 1, 2, 3A and 3B: Time to reach maximum observed concentration (tmax)	To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants.	Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose)
Parts 1, 2, 3A and 3B: Partial area under the concentration-time curve from time t1 to time t2 [AUC(t1-t2)]	To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants.	Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose)
Parts 1, 2, 3A and 3B: Terminal elimination half-life (t½λz)	To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants.	Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose)
Parts 1, 2, 3A and 3B: Mean Residence Time (MRTinf)	To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants.	Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose)
Parts 1, 2, 3A and 3B: Apparent total body clearance (CL/F)	To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants.	Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose)
Parts 1, 2, 3A and 3B: Apparent volume of distribution based on the terminal (Vz/F)	To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants.	Parts 1 and 3A: From Day 1 (pre-dose) to Day 4 (72-hour post dose); Parts 2 and 3B: From Day 1 (pre-dose) to Day 10 (48-hour post dose)
Parts 1, 2, 3A and 3B: Individual and cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)]	To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants.	Parts 1 and 3A: Up to Day 2; Parts 2 and 3B: Days 1, 2, 8, 9
Parts 1, 2, 3A and 3B: Individual and cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 [fe(t1-t2)]	To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants.	Parts 1 and 3A: Up to Day 2; Parts 2 and 3B: Days 1, 2, 8, 9
Parts 1, 2, 3A and 3B: Renal clearance (CLR)	To characterize the PK of active drug and pro-drug following oral administration of single and multiple ascending doses of AZD8965 in healthy participants.	Parts 1 and 3A: Up to Day 2; Parts 2 and 3B: Days 1, 2, 8, 9
Parts 2 and 3B: Area under concentration-time curve in the dosing interval (AUCtau)	To characterize the PK of active drug and pro-drug following oral administration of multiple ascending doses of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 10 (48-hour post dose)
Parts 2 and 3B: Accumulation ratio for AUC (Rac AUC)	To characterize the PK of active drug and pro-drug following oral administration of multiple ascending doses of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 10 (48-hour post dose)
Parts 2 and 3B: Accumulation ratio for Cmax (Rac Cmax)	To characterize the PK of active drug and pro-drug following oral administration of multiple ascending doses of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 10 (48-hour post dose)
Parts 2 and 3B: Temporal Change Parameter (TCP)	To characterize the PK of active drug and pro-drug following oral administration of multiple ascending doses of AZD8965 in healthy participants.	From Day 1 (pre-dose) to Day 10 (48-hour post dose)
Part 4: Number of participants with AEs and SAEs	To assess the safety and tolerability of AZD8965 under fasted and fed (after intake of a high fat meal) conditions in healthy participants.	SAEs: From Screening (Day -28) to 6 weeks; AEs: From Day 1 to 6 weeks

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): August 2, 2024
• Primary Completion (Actual): June 1, 2025
• Study Completion (Actual): November 15, 2025

Study Registration Dates

• First Submitted: July 9, 2024
• First Submitted That Met QC Criteria: July 9, 2024
• First Posted (Actual): July 16, 2024

Study Record Updates

• Last Update Posted (Actual): December 11, 2025
• Last Update Submitted That Met QC Criteria: December 5, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Food Effect; Idiopathic Pulmonary Fibrosis; Lung disease
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases, Interstitial; Pulmonary Fibrosis; Lung Diseases; Idiopathic Pulmonary Fibrosis
• Other Study ID Numbers: D6960C00001

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