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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
41
AZD4144 will be administered orally.
Research Site
Sofia, Bulgaria
Research Site
Bucharest, Romania
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From Day 1 to Day 14
Terminal elimination half-life (t½λz)
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To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From Day 1 to Day 4
Number of Treatment Emergent Adverse Events (TEAEs)
To evaluate the safety and tolerability of AZD4144 single dose in participants with severe renal impairment, ESKD, and their healthy controls.
Time frame: From Day 1 to Follow-up (Day 14/28)