A Study to Investigate the Pharmacokinetics, Safety, and Tolerability of AZD4144 in Participants With Severe Renal Impairment, End-stage Kidney Disease, and in Healthy Participants

A Single Dose, Non-randomised, Open-label, Parallel Group Study to Assess the Pharmacokinetics, Safety, and Tolerability of AZD4144 in Participants With Severe Renal Impairment, End-stage Kidney Disease, and in Healthy Participants

A study to investigate the pharmacokinetics, safety, and tolerability of AZD4144 in participants with severe renal impairment, end-stage kidney disease, and in healthy participants.

Study Overview

• Status: Completed
• Conditions: Renal Impairment; Healthy Participants; End-stage Kidney Disease
• Intervention / Treatment: Drug: AZD4144

Detailed Description

This is an open-label, single dose, non-randomised, parallel group, Phase I study to assess the pharmacokinetics, safety, and tolerability of AZD4144 in male and female participants with severe renal impairment and end-stage kidney disease (ESKD) compared with healthy control participants.

The study will comprise of:

• A Screening Period of 21 days.
• Cohort 1, 2, 4, and 5: a single Treatment Period with an in-clinic period of 7 days.
• Cohort 3: two Treatment Periods each with an in-clinic period of 7 days, and a washout period of 6 days after the in-clinic treatment period.
• A Follow-up visit 7 days following discharge.

• Study Type: Interventional
• Enrollment (Actual): 41
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1612
    • Research Site
• Romania
  • Bucharest, Romania, 010731
    • Research Site

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Healthy Matched Control Participants Only (Cohort 2):

• Stable renal function (for example, no clinically significant change in an estimated glomerular filtration rate (eGFR) within 3 months or longer prior to study the Screening Visit), as determined by the investigator.
• Have an eGFR of ≥ 90 milliliter/minute/1.73m2 (mL/min/1.73m2) as determined via the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula without race.

Renally Impaired Participants Only (Cohorts 1, 4 and 5)

• Participants who have renal impairments.
• Cohort 1 participants with severe renal impairment must have an eGFR ≥ 15 to < 30 mL/min/1.73m2 not on dialysis. Cohort 1 should have at least 3 participants with eGFR ≤ 20 mL/min/1.73m2.
• Cohort 4 participants with moderate renal impairment must have an eGFR of ≥ 30 to < 60 mL/min/1.73m2.
• Cohort 5 participants with mild renal impairment must have an eGFR of ≥ 60 to < 90 mL/min/1.73m2.

Cohort 3

• Participants with ESKD on IHD must have been on stable IHD for at least 3 months prior to Visit 1.
• All renally impaired participants should be on stable standard of care for at least 4 weeks prior to Visit 1.

All cohorts:

• Body weight of at least 50 kilograms (kg) and body mass index (BMI) within the range ≥ 18 to ≤ 35 kg/m2, inclusive.
• All females must have a negative pregnancy test at the Screening Visit and on admission to the Clinical Unit.

Exclusion Criteria:

• History of QT prolongation associated with other medications that required discontinuation of that medication.
• Congenital long QT syndrome.
• Known history of primary immunodeficiency (congenital or acquired) or an underlying condition that predisposes to infection.
• Concomitant immunosuppressive, steroid treatment.
• Any clinically significant disease or disorder (eg, cardiovascular, pulmonary, gastrointestinal, liver, renal, neurological, musculoskeletal including bone fractures, endocrine including adrenal insufficiency, metabolic, malignant, psychiatric, major physical impairment) (Cohort 2).
• Renal transplant participants, participants on dialysis, and those with a history of acute kidney injury (Cohorts 1, 4, 5).
• Use of any of the prohibited medications in the 4 weeks prior to Visit 1 (Cohorts 1, 3, 4, 5).
• Participants with a known hypersensitivity to AZD4144 or any of the excipients of the product.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: AZD4144; Participants with severe renal impairment will receive a single oral dose of AZD4144 on Day 1.	Drug: AZD4144; AZD4144 will be administered orally.
Experimental: Cohort 2: AZD4144; Healthy participants with normal renal function will receive a single oral dose of AZD4144 on Day 1.	Drug: AZD4144; AZD4144 will be administered orally.
Experimental: Cohort 3: AZD4144; Participants with ESKD on intermittent haemodialysis will receive a single oral dose of AZD4144 on the first day of Treatment Period 1 and Treatment Period 2.	Drug: AZD4144; AZD4144 will be administered orally.
Experimental: Cohort 4: AZD4144; Participants with moderate renal impairment will receive a single oral dose of AZD4144 on Day 1.	Drug: AZD4144; AZD4144 will be administered orally.
Experimental: Cohort 5: AZD4144; Participants with mild renal impairment will receive a single oral dose of AZD4144 on Day 1.	Drug: AZD4144; AZD4144 will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Observed maximum plasma concentration (Cmax)	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.	From Day 1 to Day 14
Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUCinf)	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.	From Day 1 to Day 14
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast)	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.	From Day 1 to Day 14
Apparent total body clearance (CL/F)	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.	From Day 1 to Day 14
Non-renal clearance of drug from plasma (CLNR/F)	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.	From Day 1 to Day 14
Apparent volume of distribution based on the terminal phase (Vz/F)	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.	From Day 1 to Day 14
Terminal elimination half-life (t½λz)	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.	From Day 1 to Day 14
Renal clearance of drug from plasma (CLR)	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.	From Day 1 to Day 4
Amount excreted (Ae)	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.	From Day 1 to Day 4
Percentage of dose excreted unchanged in urine (fe)	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.	From Day 1 to Day 4
Number of Treatment Emergent Adverse Events (TEAEs)	To evaluate the safety and tolerability of AZD4144 single dose in participants with severe renal impairment, ESKD, and their healthy controls.	From Day 1 to Follow-up (Day 14/28)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Treatment Emergent Adverse Events (TEAEs)	To evaluate the safety and tolerability of AZD4144 single dose in participants with severe renal impairment, ESKD, and their healthy controls.	From Day 1 to Follow-up (Day 14/28)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2024
• Primary Completion (Actual): April 23, 2025
• Study Completion (Actual): April 23, 2025

Study Registration Dates

• First Submitted: November 15, 2024
• First Submitted That Met QC Criteria: November 15, 2024
• First Posted (Actual): November 18, 2024

Study Record Updates

• Last Update Posted (Actual): April 7, 2026
• Last Update Submitted That Met QC Criteria: April 2, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Chronic kidney disease; Estimated glomerular filtration rate; Intermittent haemodialysis
• Additional Relevant MeSH Terms: Urogenital Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Pathological Conditions, Signs and Symptoms; Renal Insufficiency; Kidney Failure, Chronic; Renal Insufficiency, Chronic
• Other Study ID Numbers: D9440C00003; 2024-513848-28-00 (Registry Identifier: EU Clinical Trials)

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 is 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: No
• Studies a U.S. FDA-regulated device product: No