A Study to Assess the Pharmacokinetics (uptake of drugs by the body), Safety and Tolerability of AZD4831 in Participants with Severe Renal Impairment and Healthy Volunteers

Study identifier:D6580C00009

ClinicalTrials.gov identifier:NCT04949438

EudraCT identifier:2019-003498-25

CTIS identifier:N/A

Study Complete

Official Title

A Single Dose, Non-Randomised, Open-Label, Parallel Group Study to Assess the Pharmacokinetics, Safety and Tolerability of AZD4831 in Participants with Severe Renal Impairment and Healthy Volunteers

Medical condition

Renal Impairment

Phase

Phase 1

Healthy volunteers

Yes

Study drug

AZD4831

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 80 Years

Date

Study Start Date: 21 Jan 2022

Primary Completion Date: 04 Mar 2022

Study Completion Date: 04 Mar 2022

Study design

Allocation: Non-randomized
Endpoint Classification: -
Intervention Model: Parallel Assignment
Masking: -
Primary Purpose: Treatment

Verification:

Verified 01 Feb 2024 by AstraZeneca

Collaborators

PAREXEL

Inclusion and exclusion criteria

Inclusion Criteria

- All participants must be 18 to 80 (inclusive) years of age, at the time of signing the informed consent.
- The age of participants in Cohort 2 (matched healthy volunteers) must not be lesser than 10 years below the lowest age in Cohort 1 (participants with severe renal impairment) or greater than 10 years above the highest age in Cohort 1.
Healthy volunteers only (Cohort 2):
- Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
- An eGFR of ≥90 mL/min/1.73m^2 as determined at screening using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
Participants with severe renal impairment only (Cohort 1):
- An eGFR of ≥15 to <30 mL/min/1.73m^2 as determined at screening using the CKD-EPI formula.
- Stable renal function.
- If participants are on statin, ACEi/ARB, beta-blocker, diuretic or on any other cardiorenal relevant treatment, the dose should be stable at least 2 weeks prior to screening (Visit 1).
- Body weight of at least 50 kg and body mass index (BMI) within the range ≥18 to ≤35 kg/m^2.
- BMI of participants in Cohort 2 (healthy volunteers) must not be more than 20% below the lowest BMI in Cohort 1 (participants with severe renal impairment) or more than 20% above the highest BMI in Cohort 1.
- Male or female of non-childbearing potential.
- There should be an equal number of male and female participants in Cohort 2 (healthy volunteers) as in Cohort 1 (participants with severe renal impairment).
(a) Male participants: All male participants should use methods of contraception consistent with local regulations for those participating in clinical studies.
(b) Highly effective birth control methods are defined as those that can achieve a failure rate of less than 1% per year when used consistently and correctly
(c) Female participants: Must have a negative serum pregnancy test at screening and admission to the study centre (Day −1), must not be lactating and must be of
non-childbearing potential confirmed at screening.
- Male participants should not donate sperm for the duration of the study and for at least 90 days after the last study follow-up visit.
- Provision of signed and dated written Optional Genetic Research Information informed consent prior to collection of samples for optional genetic research.

Exclusion Criteria

- Any evidence of a clinically significant disease or disorder.
- Positive hepatitis C antibody, hepatitis B virus surface antigen, hepatitis B virus core antibody, or human immunodeficiency virus I or II at screening (Visit 1).
- History of drug or alcohol abuse within 1 year of screening or positive test for drugs of abuse and alcohol at screening and admission to the study centre.
- History of allergy/hypersensitivity to drugs with a similar chemical structure or class to AZD4831or any of the excipients of the product.
- Any of the following signs or confirmation of Corona Virus 2019 (COVID-19) infection
a. Participant has a positive severe acute respiratory syndrome coronavirus 2 reverse transcription-polymerase chain reaction test result within 2 weeks before screening (Visit 1) or between screening and admission to study centre (Visit 2).
(i) Clinical signs and symptoms consistent with COVID-19 (eg, fever, dry cough, dyspnoea, sore throat, fatigue) 2 weeks before screening (Visit 1) or between screening and admission to study centre (Visit 2).
(ii) Participant has been previously hospitalised with COVID-19 infection within the last 3 months.
Healthy volunteers only (Cohort 2):
- History or presence of gastrointestinal, hepatic or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs.
Participants with severe renal impairment only (Cohort 1):
- Renal transplant participants or participants on dialysis.
- Use of concurrent medication, which affect creatinine clearance such as cephalosporin antibiotics, ascorbic acid, trimethoprim, cimetidine, or quinine within days of admission to the study centre (Day −1).
- Use of drugs with enzyme-inducing properties such as St John’s Wort within 7 days or 5 half-lives (whichever is longer) prior to screening (Visit 1).
- Any concomitant medications known to be associated with Torsades de Pointes or strong cytochrome P450 3A4 (CYP3A4) inducers or inhibitors.
Healthy volunteers only (Cohort 2):
- Use of any prescribed or non-prescribed medication including antacids, analgesics (other than paracetamol), herbal remedies, megadose vitamins and minerals within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the study intervention and until completion of the follow-up visits.

No locations available

Arms	Assigned Interventions
Experimental: Cohort 1: Participants with severe renal impairment Participants with severe renal impairment will receive a single oral dose of AZD4831 on Day 1.	Drug: AZD4831 Participants will receive a single dose of AZD4831 administered with 240 mL of water after an overnight fast of at least 10 hours.
Experimental: Cohort 2 :Healthy participants Healthy participants will receive a single oral dose of AZD4831 on Day 1.	Drug: AZD4831 Participants will receive a single dose of AZD4831 administered with 240 mL of water after an overnight fast of at least 10 hours.

Documents available

redacted CSR Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

[email protected]