A Study to Investigate the Pharmacokinetics, Safety and Tolerability of AZD5462 in Participants With Renal Impairment (GLITTER)

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

The purpose of this study is to assess the pharmacokinetics (PK), safety, and tolerability of AZD5462 in participants with impaired renal function.

Study Overview

• Status: Completed
• Conditions: Renal Impairment
• Intervention / Treatment: Drug: AZD5462

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1612
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Participants with severe renal impairment (eGFR ≥ 15 to < 30 mL/min/1.73 m2, not requiring dialysis).	Drug: AZD5462; Participants will receive AZD5462 orally.
Experimental: Cohort 2; Participants who are healthy control (eGFR ≥ 90 mL/min/1.73 m2) matched at a group level to Cohort 1.	Drug: AZD5462; Participants will receive AZD5462 orally.
Experimental: Cohort 3 (conditional); Participants with moderate renal impairment (eGFR ≥ 30 to < 60 mL/min/1.73 m2).	Drug: AZD5462; Participants will receive AZD5462 orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under plasma concentration-time curve from time 0 to infinity (AUCinf)	The AUCinf of a single oral dose of AZD5462 in participants with renal impairment compared with healthy control participants matched at a group level will be assessed.	Day 1 to Day 4
Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUClast)	The AUClast of a single oral dose of AZD5462 in participants with renal impairment compared with healthy control participants matched at a group level will be assessed.	Day 1 to Day 4
Time to reach maximum observed plasma concentration (tmax)	The tmax of a single oral dose of AZD5462 in participants with renal impairment compared with healthy control participants matched at a group level will be assessed.	Day 1 to Day 4
Maximum observed plasma concentration (Cmax)	The Cmax of a single oral dose of AZD5462 in participants with renal impairment compared with healthy control participants matched at a group level will be assessed.	Day 1 to Day 4
Terminal elimination rate constant (λz)	The λz of a single oral dose of AZD5462 in participants with renal impairment compared with healthy control participants matched at a group level will be assessed.	Day 1 to Day 4
Terminal elimination half-life (t½λz)	The t½λz of a single oral dose of AZD5462 in participants with renal impairment compared with healthy control participants matched at a group level will be assessed.	Day 1 to Day 4
Apparent total body clearance (CL/F)	The CL/F of a single oral dose of AZD5462 in participants with renal impairment compared with healthy control participants matched at a group level will be assessed.	Day 1 to Day 4
Non-renal clearance of drug from plasma (CLNR/F)	The CLNR/F of a single oral dose of AZD5462 in participants with renal impairment compared with healthy control participants matched at a group level will be assessed.	Day 1 to Day 4
Apparent volume of distribution based on the terminal phase (Vz/F)	The Vz/F of a single oral dose of AZD5462 in participants with renal impairment compared with healthy control participants matched at a group level will be assessed.	Day 1 to Day 4
Renal clearance of drug (CLR)	The CLR of a single oral dose of AZD5462 in participants with renal impairment compared with healthy control participants matched at a group level will be assessed.	Day 1 to Day 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Adverse Event (AEs)	The safety and tolerability of a single oral dose of AZD5462 in participants with renal impairment and healthy control participants matched at a group level will be assessed.	Day 1 to Day 7

Collaborators and Investigators

• Sponsor: AstraZeneca

Publications and helpful links

Helpful Links

• Redacted CSR synopsis
• results posted on www.astrazenecaclinicaltrials.com

Study record dates

Study Major Dates

• Study Start (Actual): November 18, 2024
• Primary Completion (Actual): December 23, 2024
• Study Completion (Actual): December 23, 2024

Study Registration Dates

• First Submitted: October 25, 2024
• First Submitted That Met QC Criteria: October 25, 2024
• First Posted (Actual): October 28, 2024

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: November 27, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Renal impairment
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency
• Other Study ID Numbers: D9090C00010; 2024-514359-14-00 (Registry Identifier: EU CT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure."Yes",indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment athttps://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environmentVivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No