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

Phase 1

Completed

• Conditions: Renal Impairment; End-stage Kidney Disease; Healthy Participants
• Interventions: Drug: AZD4144

• Registration Number: NCT06693765
• Lead Sponsor: AstraZeneca

Brief Summary

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

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 and 2: 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 Timeline

• Study First Submitted: 2024-11-15
• Study First Submitted QC: 2024-11-15
• Study Start: 2024-11-18
• Study First Posted: 2024-11-18
• Primary Completion: 2025-04-23
• Study Completion: 2025-04-23
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-08
• Last Update Posted: 2025-05-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 41

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 (Cohort 1)

• Participants who have renal impairments.
• 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 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 (Cohort 1).
• Use of any of the prohibited medications in the 4 weeks prior to Visit 1 (Cohorts 1 and 3).
• Participants with a known hypersensitivity to AZD4144 or any of the excipients of the product.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1: AZD4144	AZD4144	Participants with severe renal impairment will receive a single oral dose of AZD4144 on Day 1.
Cohort 2: AZD4144	AZD4144	Healthy participants with normal renal function will receive a single oral dose of AZD4144 on Day 1.
Cohort 3: AZD4144	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.

Primary Outcome Measures

Name	Time	Method
Observed maximum plasma concentration (Cmax)	From Day 1 to Day 14	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUCinf)	From Day 1 to Day 14	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast)	From Day 1 to Day 14	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
Apparent total body clearance (CL/F)	From Day 1 to Day 14	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
Non-renal clearance of drug from plasma (CLNR/F)	From Day 1 to Day 14	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
Apparent volume of distribution based on the terminal phase (Vz/F)	From Day 1 to Day 14	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
Terminal elimination half-life (t½λz)	From Day 1 to Day 14	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
Renal clearance of drug from plasma (CLR)	From Day 1 to Day 4	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
Amount excreted (Ae)	From Day 1 to Day 4	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
Percentage of dose excreted unchanged in urine (fe)	From Day 1 to Day 4	To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Research Site; 🇷🇴 Bucuresti, Romania