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

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

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.

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 (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.

Keywords: intermittent haemodialysis chronic kidney disease estimated glomerular filtration rate