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

NCT04949438 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: D6580C00009
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a study to compare AZD4831 pharmacokinetic (PK) parameters between participants with severe renal impairment and matched healthy volunteers following a single dose administration.

Conditions

Renal Impairment

Keywords

AZD4831; Pharmacokinetics; Estimated glomerular filtration rate

Outcome Measures

Primary Outcomes (9)

• Maximum observed plasma concentration (Cmax)

  Assessment of Cmax of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.

  From Day 1 to Day 15

• Time to reach maximum observed plasma concentration (tmax)

  Assessment of tmax of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.

  From Day 1 to Day 15

• Half-life associated with terminal slope (λz) of a semi-logarithmic concentration-time curve (t½λz)

  Assessment of t½λz of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.

  From Day 1 to Day 15

• Apparent total body clearance of drug from plasma after extravascular administration (CL/F)

  Assessment of CL/F of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.

  From Day 1 to Day 15

• Apparent total non-renal body clearance of drug from plasma after extravascular administration (CLNR/F)

  Assessment of CLNR/F of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.

  From Day 1 to Day 15

• Apparent volume of distribution during the terminal phase after extravascular administration (Vz/F)

  Assessment of Vz/F of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.

  From Day 1 to Day 15

• Area under the plasma concentration-curve from time zero to time of last quantifiable concentration (AUClast)

  Assessment of AUClast of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.

  From Day 1 to Day 15

• Area under plasma concentration-time curve from time zero to infinity (AUCinf)

  Assessment of AUCinf of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.

  From Day 1 to Day 15

• Renal clearance of drug from plasma (CLR)

  Assessment of CLR of a single oral dose of AZD4831 in participants with severe renal impairment compared with that in matched healthy volunteers.

  Days 1 and 2

Secondary Outcomes (1)

• Number of participants with adverse events

  From Screening (Day -21 to Day -1) until Day 15 or Early Termination Visit

Study Arms (2)

Cohort 1: Participants with severe renal impairment

EXPERIMENTAL

Participants with severe renal impairment will receive a single oral dose of AZD4831 on Day 1.

Drug: AZD4831

Cohort 2 :Healthy participants

EXPERIMENTAL

Healthy participants will receive a single oral dose of AZD4831 on Day 1.

Drug: AZD4831

Interventions

AZD4831 DRUG

Participants will receive a single dose of AZD4831 administered with 240 mL of water after an overnight fast of at least 10 hours.

Cohort 1: Participants with severe renal impairment; Cohort 2 :Healthy participants

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Male participants: All male participants should use methods of contraception consistent with local regulations for those participating in clinical studies.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (1)

Research Site

Sofia, 1612, Bulgaria

Location

MeSH Terms

Conditions

Renal Insufficiency

Interventions

AZD4831

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2021
• First Posted: July 2, 2021
• Study Start: January 21, 2022
• Primary Completion: March 4, 2022
• Study Completion: March 4, 2022
• Last Updated: April 5, 2022

Record last verified: 2022-03

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 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 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

BU (1)