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

NCT06502379 | Completed Phase 1 FDA Drug

• 1 other identifier: D6960C00001
• Study Type: interventional
• Target: 147
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Participants

Keywords

Idiopathic Pulmonary Fibrosis; Lung disease; Pharmacokinetics; Food Effect

Outcome Measures

Primary Outcomes (18)

• 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 Outcomes (17)

• Parts 1, 2, 3A and 3B: Maximum observed drug concentration (Cmax)

  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)

  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)

  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)

  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)]

  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)

Study Arms (14)

Part 1: SAD Cohort 1 - AZD8965 (Dose 1)

EXPERIMENTAL

Participants will receive a single dose of AZD8965 (Dose 1) or matching placebo to AZD8965 on Day 1.

Drug: AZD8965; Other: Placebo

Part 1: SAD Cohort 2 - AZD8965 (Dose 2)

EXPERIMENTAL

Participants will receive a single dose of AZD8965 (Dose 2) or matching placebo to AZD8965 on Day 1.

Drug: AZD8965; Other: Placebo

Part 1: SAD Cohort 3 - AZD8965 (Dose 3)

EXPERIMENTAL

Participants will receive a single dose of AZD8965 (Dose 3) or matching placebo to AZD8965 on Day 1.

Drug: AZD8965; Other: Placebo

Part 1: SAD Cohort 4 - AZD8965 (Dose 4)

EXPERIMENTAL

Participants will receive a single dose of AZD8965 (Dose 4) or matching placebo to AZD8965 on Day 1.

Drug: AZD8965; Other: Placebo

Part 1: SAD Cohort 5 - AZD8965 (Dose 5)

EXPERIMENTAL

Participants will receive a single dose of AZD8965 (Dose 5) or matching placebo to AZD8965 on Day 1.

Drug: AZD8965; Other: Placebo

Part 2: MAD Cohort 1 - AZD8965 (Dose 1)

EXPERIMENTAL

Participants will receive multiple doses of AZD8965 (Dose 1) or matching placebo to AZD8965 from Day 1 to Day 8.

Drug: AZD8965; Other: Placebo

Part 2: MAD Cohort 2 - AZD8965 (Dose 2)

EXPERIMENTAL

Participants will receive multiple doses of AZD8965 (Dose 2) or matching placebo to AZD8965 from Day 1 to Day 8.

Drug: AZD8965; Other: Placebo

Part 2: MAD Cohort 3 - AZD8965 (Dose 3)

EXPERIMENTAL

Participants will receive multiple doses of AZD8965 (Dose 3) or matching placebo to AZD8965 from Day 1 to Day 8.

Drug: AZD8965; Other: Placebo

Part 3A: SAD Cohort 1 (Japanese) - AZD8965 (Dose 1)

EXPERIMENTAL

Japanese participants will receive a single dose of AZD8965 (Dose 1) or matching placebo to AZD8965 on Day 1.

Drug: AZD8965; Other: Placebo

Part 3A: SAD Cohort 2 (Japanese) - AZD8965 (Dose 2)

EXPERIMENTAL

Japanese participants will receive a single dose of AZD8965 (Dose 2) or matching placebo to AZD8965 on Day 1.

Drug: AZD8965; Other: Placebo

Part 3A: SAD Cohort 3 (Chinese) - AZD8965 (Dose 1)

EXPERIMENTAL

Chinese participants will receive a single dose of AZD8965 (Dose 1) or matching placebo to AZD8965 on Day 1.

Drug: AZD8965; Other: Placebo

Part 3B: Single and multiple ascending dose (SMAD) Cohort 1 (Japanese) - AZD8965 (Dose 1)

EXPERIMENTAL

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.

Drug: AZD8965; Other: Placebo

Part 3B: SMAD Cohort 2 (Chinese) - AZD8965 (Dose 1)

EXPERIMENTAL

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.

Drug: AZD8965; Other: Placebo

Part 4: Food Effect Cohort - AZD8965

EXPERIMENTAL

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

Interventions

AZD8965 DRUG

AZD8965 will be administered orally.

Part 1: SAD Cohort 1 - AZD8965 (Dose 1); Part 1: SAD Cohort 2 - AZD8965 (Dose 2); Part 1: SAD Cohort 3 - AZD8965 (Dose 3); Part 1: SAD Cohort 4 - AZD8965 (Dose 4); Part 1: SAD Cohort 5 - AZD8965 (Dose 5); Part 2: MAD Cohort 1 - AZD8965 (Dose 1); Part 2: MAD Cohort 2 - AZD8965 (Dose 2); Part 2: MAD Cohort 3 - AZD8965 (Dose 3); Part 3A: SAD Cohort 1 (Japanese) - AZD8965 (Dose 1); Part 3A: SAD Cohort 2 (Japanese) - AZD8965 (Dose 2); Part 3A: SAD Cohort 3 (Chinese) - AZD8965 (Dose 1); Part 3B: SMAD Cohort 2 (Chinese) - AZD8965 (Dose 1); Part 3B: Single and multiple ascending dose (SMAD) Cohort 1 (Japanese) - AZD8965 (Dose 1); Part 4: Food Effect Cohort - AZD8965

Placebo OTHER

Placebo will be administered orally.

Part 1: SAD Cohort 1 - AZD8965 (Dose 1); Part 1: SAD Cohort 2 - AZD8965 (Dose 2); Part 1: SAD Cohort 3 - AZD8965 (Dose 3); Part 1: SAD Cohort 4 - AZD8965 (Dose 4); Part 1: SAD Cohort 5 - AZD8965 (Dose 5); Part 2: MAD Cohort 1 - AZD8965 (Dose 1); Part 2: MAD Cohort 2 - AZD8965 (Dose 2); Part 2: MAD Cohort 3 - AZD8965 (Dose 3); Part 3A: SAD Cohort 1 (Japanese) - AZD8965 (Dose 1); Part 3A: SAD Cohort 2 (Japanese) - AZD8965 (Dose 2); Part 3A: SAD Cohort 3 (Chinese) - AZD8965 (Dose 1); Part 3B: SMAD Cohort 2 (Chinese) - AZD8965 (Dose 1); Part 3B: Single and multiple ascending dose (SMAD) Cohort 1 (Japanese) - AZD8965 (Dose 1)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• 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.
• 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:
• Born in Japan
• Have 2 Japanese biological parents and 4 Japanese grandparents.
• 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:
• Born in mainland China, Hong Kong, Macau, or Taiwan

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (1)

Research Site

Glendale, California, 91206, United States

Location

MeSH Terms

Conditions

Idiopathic Pulmonary Fibrosis; Lung Diseases

Condition Hierarchy (Ancestors)

Pulmonary Fibrosis; Lung Diseases, Interstitial; Respiratory Tract Diseases

Study Design

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

Study Record Dates

• First Submitted: July 9, 2024
• First Posted: July 16, 2024
• Study Start: August 2, 2024
• Primary Completion: June 1, 2025
• Study Completion: November 15, 2025
• Last Updated: December 11, 2025

Record last verified: 2025-11

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 refer 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. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

US (1)