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

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Renal Impairment

Treatments: Drug: AZD5462

Study type: Interventional

Funder types: Industry

Identifiers

NCT06661733

2024-514359-14-00 (Registry Identifier)

D9090C00010

Details and patient eligibility

About

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

Full 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.

Enrollment: 16 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

16 participants in 3 patient groups

Cohort 1

Experimental group

Description:

Participants with severe renal impairment (eGFR ≥ 15 to \< 30 mL/min/1.73 m2, not requiring dialysis).

Treatment:

Drug: AZD5462

Cohort 2

Experimental group

Description:

Participants who are healthy control (eGFR ≥ 90 mL/min/1.73 m2) matched at a group level to Cohort 1.

Treatment:

Drug: AZD5462

Cohort 3 (conditional)

Experimental group

Description:

Participants with moderate renal impairment (eGFR ≥ 30 to \< 60 mL/min/1.73 m2).

Treatment:

Drug: AZD5462