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

NCT ID: NCT06693765

Last Updated: 2025-09-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 41 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-11-18
• Study Completion Date: 2025-04-23

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, 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.

Conditions

Renal Impairment; End-stage Kidney Disease; Healthy Participants

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1: AZD4144

Participants with severe renal impairment will receive a single oral dose of AZD4144 on Day 1.

Group Type: EXPERIMENTAL

AZD4144

Intervention Type: DRUG

AZD4144 will be administered orally.

Cohort 2: AZD4144

Healthy participants with normal renal function will receive a single oral dose of AZD4144 on Day 1.

Group Type: EXPERIMENTAL

AZD4144

Intervention Type: DRUG

AZD4144 will be administered orally.

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.

Group Type: EXPERIMENTAL

AZD4144

Intervention Type: DRUG

AZD4144 will be administered orally.

Cohort 4: AZD4144

Participants with moderate renal impairment will receive a single oral dose of AZD4144 on Day 1.

Group Type: EXPERIMENTAL

AZD4144

Intervention Type: DRUG

AZD4144 will be administered orally.

Cohort 5: AZD4144

Participants with mild renal impairment will receive a single oral dose of AZD4144 on Day 1.

Group Type: EXPERIMENTAL

AZD4144

Intervention Type: DRUG

AZD4144 will be administered orally.

Interventions

AZD4144

AZD4144 will be administered orally.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Parexel

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Sofia, , Bulgaria

Research Site

Bucharest, , Romania

Countries

Bulgaria; Romania

Other Identifiers

2024-513848-28-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

D9440C00003

Identifier Type: -

Identifier Source: org_study_id