Clinical trial NCT06693765: 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
Official title: A Single Dose, Non-randomised, Open-label, Parallel Group Study to Assess the Pharmacokinetics, Safety, and Tolerability of AZD4144 in Participants With Severe Renal Impairment, End-stage Kidney Disease, and in Healthy Participants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
End-stage Kidney Disease
Healthy Participants
Keywords: Intermittent haemodialysis
Chronic kidney disease
Estimated glomerular filtration rate
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Parexel
First posted: 2024-11-18
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.

Primary outcomes:
measure: Observed maximum plasma concentration (Cmax)
timeFrame: From Day 1 to Day 14
measure: Area under the plasma concentration-time curve from time zero extrapolated to infinity (AUCinf)
timeFrame: From Day 1 to Day 14
measure: Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration (AUClast)
timeFrame: From Day 1 to Day 14
measure: Apparent total body clearance (CL/F)
timeFrame: From Day 1 to Day 14
measure: Non-renal clearance of drug from plasma (CLNR/F)
timeFrame: From Day 1 to Day 14
measure: Apparent volume of distribution based on the terminal phase (Vz/F)
timeFrame: From Day 1 to Day 14
measure: Terminal elimination half-life (t½λz)
timeFrame: From Day 1 to Day 14
measure: Renal clearance of drug from plasma (CLR)
timeFrame: From Day 1 to Day 4
measure: Amount excreted (Ae)
timeFrame: From Day 1 to Day 4
measure: Percentage of dose excreted unchanged in urine (fe)
timeFrame: From Day 1 to Day 4
Secondary outcomes:
measure: Number of Treatment Emergent Adverse Events (TEAEs)
timeFrame: From Day 1 to Follow-up (Day 14/28)
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: Research Site
city: Bucuresti
country: Romania
facility: Research Site
Study officials:
References: