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

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Renal Impairment; Healthy Participants; End-stage Kidney Disease

Treatments: Drug: AZD4144

Study type: Interventional

Funder types: Industry

Identifiers

NCT06693765

D9440C00003

2024-513848-28-00 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 41 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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41 participants in 5 patient groups

Cohort 1: AZD4144

Experimental group

Description:

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

Treatment:

Drug: AZD4144

Cohort 2: AZD4144

Experimental group

Description:

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

Treatment:

Drug: AZD4144

Cohort 3: AZD4144

Experimental group

Description:

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.

Treatment:

Drug: AZD4144

Cohort 4: AZD4144

Experimental group

Description:

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

Treatment:

Drug: AZD4144

Cohort 5: AZD4144

Experimental group

Description:

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

Treatment:

Drug: AZD4144