A Study to Assess the Effect AZD4831 in Japanese and Chinese Healthy Volunteers

NCT04232345 | Completed Phase 1 FDA Drug

• 1 other identifier: D6580C00008
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This study is randomized, single-blind, placebo-controlled Phase 1 study aimed to assess the safety and efficacy, pharmacokinetics and pharmacodynamics of multiple doses of oral AZD4831 in healthy Japanese and Chinese volunteers

Conditions

Heart Failure With Preserved Ejection Fraction (HFpEF)

Keywords

Randomized; Single-blind; Placebo-controlled; Multiple-ascending dose; AZD4831 oral suspension

Outcome Measures

Primary Outcomes (5)

• Number of subjects with adverse events (AEs)/serious adverse events

  To assess AEs as a variable of safety and tolerability of AZD4831 following oral administration of multiple-ascending doses at steady state in healthy Japanese and Chinese subjects.

  Screening through follow-up visit (upto 9 weeks)

• Number of subjects with abnormal blood pressure (BP) and pulse

  To assess BP and pulse rate as a variable of safety and tolerability of AZD4831 following oral administration of multiple-ascending doses at steady state in healthy Japanese and Chinese subjects.

  Screening through follow-up visit (upto 9 weeks)

• Number of subjects with abnormal electrocardiogram (ECG)

  To assess change ECG as a variable of safety and tolerability of AZD4831 following oral administration of multiple-ascending doses at steady state in healthy Japanese and Chinese subjects.

  Screening through follow-up visit (upto 9 weeks)

• Number of subjects with abnormal abnormal clinical chemistry/hematology/urinalysis

  To assess clinical chemistry/hematology/urinalysis as a variable of safety and tolerability of AZD4831 following oral administration of multiple-ascending doses at steady state in healthy Japanese and Chinese subjects.

  Screening through follow-up visit (upto 9 weeks)

• Number of subjects with abormal physical examination results

  To assess physical examination as a variable of safety and tolerability of AZD4831 following oral administration of multiple-ascending doses at steady state in healthy Japanese and Chinese subjects.

  Screening through follow-up visit (upto 9 weeks)

Secondary Outcomes (18)

• Plasma Cmax: Maximum observed plasma concentration

  Day 1: Pre-dose (pre); 0.25,0.5,1,1.5,2,3,4,6,8,12 h post-dose (post); Day 2-9: Pre; Day 10: Pre and at 0.25,0.5,1,1.5,2,3,4,6,8,12 h post; Day 11:24 and 36 h post; Day 12: 48 h post; Day 16:96,144, and 240 h post; Day 24:336 h post

• Plasma Cmax/D

  Day 1: pre; 0.25,0.5,1,1.5,2,3,4,6,8,12 h post; Day 2-9: Pre; Day 10: Pre and at 0.25,0.5,1,1.5,2,3,4,6,8,12 h post; Day 11:24 and 36 h post; Day 12: 48 h post; Day 16:96,144, and 240 h post; Day 24:336 h post

• Plasma tmax: Time to reach peak or maximum observed concentration following drug administration

  Day 1: pre; 0.25,0.5,1,1.5,2,3,4,6,8,12 h post; Day 2-9: Pre; Day 10: Pre and at 0.25,0.5,1,1.5,2,3,4,6,8,12 h post; Day 11:24 and 36 h post; Day 12: 48 h post; Day 16:96,144, and 240 h post; Day 24:336 h post

• Plasma Ctrough: Observed trough plasma concentration

  Day 1: pre; 0.25,0.5,1,1.5,2,3,4,6,8,12 h post; Day 2-9: Pre; Day 10: Pre and at 0.25,0.5,1,1.5,2,3,4,6,8,12 h post; Day 11:24 and 36 h post; Day 12: 48 h post; Day 16:96,144, and 240 h post; Day 24:336 h post

• Plasma t1/2λz: Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve

  Day 1: pre; 0.25,0.5,1,1.5,2,3,4,6,8,12 h post; Day 2-9: Pre; Day 10: Pre and at 0.25,0.5,1,1.5,2,3,4,6,8,12 h post; Day 11:24 and 36 h post; Day 12: 48 h post; Day 16:96,144, and 240 h post; Day 24:336 h post

Study Arms (6)

Cohort 1 (Part 1): AZD4831 Dose 1

EXPERIMENTAL

Randomized subjects will receive oral suspension of AZD4831 Dose 1 once daily in the morning for a period of 10 days

Drug: AZD4831

Cohort 2 (Part 1): AZD4831 Dose 2

EXPERIMENTAL

Randomized subjects will receive oral suspension of AZD4831 Dose 2 once daily in the morning for a period of 10 days.

Drug: AZD4831

Cohort 3 (Part 1): AZD4831 Dose 3

EXPERIMENTAL

Randomized subjects will receive oral suspension of AZD4831 Dose 3 once daily in the morning for a period of 10 days.

Drug: AZD4831

Cohort 4 (Part 2): AZD4831 Dose 2

EXPERIMENTAL

Randomized subjects will receive oral suspension of AZD4831 Dose 2 once daily in the morning for a period of 10 days.

Drug: AZD4831

Placebo (Part 1)

EXPERIMENTAL

Randomized subjects will receive oral suspension of placebo once daily in the morning for a period of 10 days.

Drug: Placebo

Placebo (Part 2)

EXPERIMENTAL

Randomized subjects will receive oral suspension of placebo once daily in the morning for a period of 10 days.

Drug: Placebo

Interventions

AZD4831 DRUG

Subjects will be fasted for at least 10 hours before receiving the AZD4831 in the form of an oral suspension.

Cohort 1 (Part 1): AZD4831 Dose 1; Cohort 2 (Part 1): AZD4831 Dose 2; Cohort 3 (Part 1): AZD4831 Dose 3; Cohort 4 (Part 2): AZD4831 Dose 2

Placebo DRUG

Subjects will be fasted for at least 10 hours before receiving the placebo in the form of an oral suspension.

Placebo (Part 1); Placebo (Part 2)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Gender Eligibility Details: Male Japanese and Chinese subjects aged 18-50 years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provision of signed and dated, written informed consent prior to any study specific procedures.
• Healthy male Japanese and Chinese subjects aged 18 - 50 years (inclusive at Screening) with suitable veins for cannulation or repeated venipuncture.
• A Japanese subject 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.
• A Chinese subject 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.
• Have a body mass index (BMI) between 18 and 30 kg/m2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive.
• Provision of signed, written and dated informed consent for optional genetic/biomarker research. If a subject decline to participate in the genetic component of the study, there will be no penalty or loss of benefit to the subject. The subject will not be excluded from other aspects of the study described in this protocol.

You may not qualify if:

• History of any clinically important disease or disorder which, in the opinion of the Investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject'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.
• Presence of infection(s) (particularly fungal infection), as judged by the Investigator.
• History of, or current thyroid disease.
• Any ongoing skin disorder, history of or ongoing clinically significant allergy/hypersensitivity.
• Any clinically important illness, medical/surgical procedure or trauma within 4 weeks of the first administration of investigational medicinal product (IMP).
• Any clinically significant abnormalities in clinical chemistry, hematology, or urinalysis results, as judged by the Investigator at Screening and/or Day -1.
• Alanine transaminase (ALT) not within normal range
• Aspartate aminotransferase (AST) not within normal range
• Creatinine not within normal range
• White blood cell (WBC) count not within normal range
• Hemoglobin not within normal range;
• Estimated Glomerular Filtration Rate (eGFR) not within normal range.
• Any positive result at Screening for serum hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus (HIV) type 1 and 2.
• Abnormal vital signs, after 10 minutes supine rest, at Screening and/or Day -1, defined as any of the following:

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Glendale, California, 91206, United States

Location

Related Publications (1)

• Sunnaker M, Bhattacharya C, Nelander K, Aurell M, Heijer M, Collen A, Han D, Holden J, Trebski M, Garkaviy P, Ericsson H. Pharmacokinetics and Tolerability of the Novel Myeloperoxidase Inhibitor Mitiperstat in Healthy Japanese and Chinese Volunteers. Clin Drug Investig. 2024 Nov;44(11):863-874. doi: 10.1007/s40261-024-01402-x. Epub 2024 Nov 4.

  PMID: 39495467 DERIVED

MeSH Terms

Interventions

AZD4831

Study Officials

• David Han, M.D

  PAREXEL Early Phase Clinical Unit-Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: This study is single-blind with regards to treatment (AZD4831 or placebo) at each dose level. AZD4831 and placebo will be matched for appearance and amount. Subjects randomized to placebo will receive the same volume of oral suspension as subjects on active drug.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study will be a randomized, single-blind, placebo-controlled, MAD sequential-group study in healthy Japanese (Part 1, Cohorts 1, 2, and 3) and Chinese (Part 2, Cohort 4) male subjects, conducted at a single study center. Up to 40 healthy male subjects aged 18 to 50 years (inclusive) are planned to be investigated in 4 cohorts, but up to 5 cohorts may be included if the SRC considers it necessary to repeat a dose level or if additional dose levels are required. Up to 8 subjects will participate in each cohort. Within each cohort 6 subjects will be randomly assigned to receive AZD4831 and 2 subjects to receive placebo. AZD4831 or placebo will be administered once daily for a period of 10 days. It is anticipated this will be sufficient to achieve and maintain steady state pharmacokinetic (PK) profiles for several days, permitting evaluation of the safety and tolerability of multiple dose. The subjects will stay at the study center during the whole dosing period and until 48 hours.

Study Record Dates

• First Submitted: January 3, 2020
• First Posted: January 18, 2020
• Study Start: January 16, 2020
• Primary Completion: March 11, 2021
• Study Completion: March 11, 2021
• Last Updated: April 1, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer 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 de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure

Locations

US (1)