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

NCT06693765 | Completed Phase 1

• 2 other identifiers: D9440C000032024-513848-28-00
• Study Type: interventional
• Target: 41
• Locations: 2 countries
• Sites: 2

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.

Conditions

Renal Impairment; End-stage Kidney Disease; Healthy Participants

Keywords

Intermittent haemodialysis; Chronic kidney disease; Estimated glomerular filtration rate

Outcome Measures

Primary Outcomes (10)

• 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

Secondary Outcomes (1)

• Number of Treatment Emergent Adverse Events (TEAEs)

  From Day 1 to Follow-up (Day 14/28)

Study Arms (5)

Cohort 1: AZD4144

EXPERIMENTAL

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

Drug: AZD4144

Cohort 2: AZD4144

EXPERIMENTAL

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

Drug: AZD4144

Cohort 3: AZD4144

EXPERIMENTAL

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

Cohort 4: AZD4144

EXPERIMENTAL

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

Drug: AZD4144

Cohort 5: AZD4144

EXPERIMENTAL

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

Drug: AZD4144

Interventions

AZD4144 DRUG

AZD4144 will be administered orally.

Cohort 1: AZD4144; Cohort 2: AZD4144; Cohort 3: AZD4144; Cohort 4: AZD4144; Cohort 5: AZD4144

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (2)

Research Site

Sofia, 1612, Bulgaria

Location

Research Site

Bucharest, 010731, Romania

Location

MeSH Terms

Conditions

Renal Insufficiency; Kidney Failure, Chronic; Renal Insufficiency, Chronic

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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: November 15, 2024
• First Posted: November 18, 2024
• Study Start: November 18, 2024
• Primary Completion: April 23, 2025
• Study Completion: April 23, 2025
• Last Updated: September 11, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• 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.
• 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.

Locations

BU (1); RO (1)