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.

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.

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.

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.

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.

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.