End-stage Kidney Disease, Healthy Participants, Renal Impairment
Conditions
Keywords
Intermittent haemodialysis, Chronic kidney disease, Estimated glomerular filtration rate
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.
Detailed 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.
Interventions
DRUGAZD4144
AZD4144 will be administered orally.
Sponsors
AstraZeneca
Parexel
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Observed maximum plasma concentration (Cmax) | From Day 1 to Day 14 | To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants. |
| Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUCinf) | From Day 1 to Day 14 | To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants. |
| Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast) | From Day 1 to Day 14 | To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants. |
| Apparent total body clearance (CL/F) | From Day 1 to Day 14 | To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants. |
| Non-renal clearance of drug from plasma (CLNR/F) | From Day 1 to Day 14 | To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants. |
| Apparent volume of distribution based on the terminal phase (Vz/F) | From Day 1 to Day 14 | To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants. |
| Terminal elimination half-life (t½λz) | From Day 1 to Day 14 | To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants. |
| Renal clearance of drug from plasma (CLR) | From Day 1 to Day 4 | To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants. |
| Amount excreted (Ae) | From Day 1 to Day 4 | To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants. |
| Percentage of dose excreted unchanged in urine (fe) | From Day 1 to Day 4 | To assess the PK of a single oral dose of AZD4144 in participants with severe renal impairment and ESKD compared with healthy control participants. |
| Number of Treatment Emergent Adverse Events (TEAEs) | From Day 1 to Follow-up (Day 14/28) | To evaluate the safety and tolerability of AZD4144 single dose in participants with severe renal impairment, ESKD, and their healthy controls. |
Countries
Bulgaria, Romania
Outcome results
None listed