Clinical trial NCT06661733: A Study to Investigate the Pharmacokinetics, Safety and Tolerability of AZD5462 in Participants With Renal Impairment
Official title: A Phase I Single Dose, Non-Randomised, Open-Label, Parallel Group Study to Assess the Pharmacokinetics, Safety and Tolerability of AZD5462 in Participants With Renal Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Renal Impairment
Keywords: Renal impairment
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-10-28
Enrollment: 16
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: The purpose of this study is to assess the pharmacokinetics (PK), safety, and tolerability of AZD5462 in participants with impaired renal function.

Detailed description: This is a Phase I, single dose, non-randomised, open-label, parallel group study to assess the PK, safety, and tolerability of AZD5462 in male and female participants (females of non-childbearing potential) with renal impairment.

This study consists of 3 cohorts:

1. Cohort 1: Participants with severe renal impairment (eGFR ≥ 15 to \< 30mL/min/1.73 m2, not requiring dialysis).
2. Cohort 2: Participants who are healthy control (eGFR ≥ 90 mL/min/1.73 m2) matched at a group level to Cohort 1.
3. Cohort 3 (conditional): Participants with moderate renal impairment (eGFR ≥ 30 to \< 60mL/min/1.73 m2).

This study comprises of three periods:

* Screening period: 21 days
* In-patient (Treatment) period: 4 days
* Out-patient visit: On Day 4, participants will return to the study site to undergo safety assessments and provide blood samples 72 hours post-dose. Participants may stay at the study site for this visit if preferred.
* Follow-up visit: On Day 7 (± 2), participants will return to the study site for safety assessments.

The duration of the study for an individual participant from the Screening Visit to the Follow-up Visit will be approximately 4 weeks.

Eligibility criteria: Main Inclusion Criteria:

Healthy matched participants (cohort2):

* Participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, laboratory tests, and cardiac monitoring.
* Stable renal function (eg, no clinically significant change in an eGFR within 3 months or longer prior to study screening), as determined by the investigator.
* An eGFR of ≥ 90 mL/min/1.73 m2, as determined at Screening Visit using the CKD-EPI 2021 creatinine only equation.

Participants With Renal Impairment:

* Participants with severe renal impairment (Cohort 1) must have an eGFR ≥ 15 to \< 30 mL/min/1.73 m2, as determined at Screening Visit using the CKD-EPI 2021 creatinine only equation and not on dialysis.
* Participants with moderate renal impairment (Cohort 3) must have an eGFR of ≥ 30 to \< 60 mL/min/1.73 m2, as determined at Screening Visit using the CKD-EPI 2021 creatinine only equation and not on dialysis.
* Stable renal impairment (eg, no clinically significant change in eGFR within 3 months or longer prior to study screening), for both Cohorts 1 and 3, as determined by the investigator.
* BMI within the range ≥ 18 to \< 35 kg/m2, inclusive.
* Females of non-childbearing potential and males.

Main Exclusion Criteria:

* As judged by the investigator, any evidence of clinically significant disease or abnormal findings in screening assessments which in the investigator's opinion makes it undesirable for the participant to participate in the study.
* Positive HCV Ab, HBsAg, or HBcAb, HIV at screening.

Healthy Matched Participants (Cohort 2):

• Any clinically significant disease or disorder (eg, cardiovascular, pulmonary, gastrointestinal, hepatic, renal, neurological, musculoskeletal including bone fractures, endocrine including adrenal insufficiency, metabolic, malignant, psychiatric, major physical impairment, or coagulation disorders) which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or influence the result of the study, or the participant's ability to participate in the study.

Participants With Renal Impairment:

* Presence of unstable medical (eg, diabetes) or psychological conditions which, in the opinion of the investigator, would compromise the participant's safety or successful participation in this study.
* Renal transplant participants, participants on dialysis, and those with a history of acute kidney injury. Use of concurrent medication, which affects creatinine clearance such as cephalosporin antibiotics, ascorbic acid, trimethoprim, cimetidine, quinine within 7 days of Day -1.

Primary outcomes:
measure: Area under plasma concentration-time curve from time 0 to infinity (AUCinf)
timeFrame: Day 1 to Day 4
measure: Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast)
timeFrame: Day 1 to Day 4
measure: Time to reach maximum observed plasma concentration (tmax)
timeFrame: Day 1 to Day 4
measure: Maximum observed plasma concentration (Cmax)
timeFrame: Day 1 to Day 4
measure: Terminal elimination rate constant (λz)
timeFrame: Day 1 to Day 4
measure: Terminal elimination half-life (t½λz)
timeFrame: Day 1 to Day 4
measure: Apparent total body clearance (CL/F)
timeFrame: Day 1 to Day 4
measure: Non-renal clearance of drug from plasma (CLNR/F)
timeFrame: Day 1 to Day 4
measure: Apparent volume of distribution based on the terminal phase (Vz/F)
timeFrame: Day 1 to Day 4
measure: Renal clearance of drug (CLR)
timeFrame: Day 1 to Day 2
Secondary outcomes:
measure: Number of participants with Adverse Event (AEs)
timeFrame: Day 1 to Day 7
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: Research Site
Study officials:
References: