NCT06592482

A Phase I Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD0780

A Phase I, Single-Dose, Non-Randomised, Open-Label, Parallel Group Study to Investigate the Effect of Renal Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD0780

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: AstraZeneca · Industry
• Sex: All
• Age: 18 Years – 85 Years
• Healthy volunteers: Accepted

Summary

This is a Phase I, multi-centre, single-dose, non-randomised, open-label, parallel-group study to examine the PK, safety, and tolerability of AZD0780 in male and female participants (females of non-childbearing potential) with severe renal impairment not on dialysis, end-stage renal disease (ESRD) on intermittent haemodialysis (HD), or moderate renal impairment (optional) compared with male and female participants (females of non-childbearing potential) with normal renal function. Potential participants will be screened to assess their eligibility to enter the study up to 4 weeks prior to administration of study intervention. Eligible participants will be admitted to the study site on Day -1. On Day 1, an "A" single oral dose of AZD0780 will be administered, and participants will be confined to the study site until after assessments are completed on Day 11.

Detailed description

This is a Phase I, multi-centre, single-dose, non-randomised, open-label, parallel-group study to examine the PK, safety, and tolerability of AZD0780 in male and female participants (females of non-childbearing potential) with severe renal impairment not on dialysis, end-stage renal disease (ESRD) on intermittent haemodialysis (HD), or moderate renal impairment (optional) compared with male and female participants (females of non-childbearing potential) with normal renal function. Participants will be assigned to the following groups based on body surface area-adjusted estimated glomerular filtration rate (eGFR) determined by a local laboratory at screening by the Chronic Kidney Disease Epidemiology Collaboration Creatinine Equation (2021) using serum creatinine: Group 1: Participants with severe renal impairment (eGFR \< 30 mL/min), not on dialysis. Group 2: Participants with ESRD (eGFR \< 15 mL/min) on a stable intermittent HD schedule for at least 3 months prior to planned dosing. Group 3: Participants with normal renal function demographically matched by sex,age, and body mass index (BMI) to the impaired participants (eGFR of ≥90 mL/min). Group 4 (optional): Participants with moderate renal impairment (eGFR ≥ 30 to \< 60 mL/min). Initially, participants with severe renal impairment (Group 1) and ESRD (Group 2) will be enrolled, along with matching participants with normal renalfunction. An analysis of PK datamay be conducted to determine study progression. The decision to trigger the PK analysis and/or proceed with an evaluation of participants with moderate renal impairment (Group 4) will be made by the sponsor. Each matched participant with normal renal function (Group 3) enrolled in the study will be demographically matched by sex, age (±10 years), and BMI (±20% kg/m2; data obtained at screening) to an enrolled renal impairment participant. Participants with normal renal function cannot be matched to more than one renally impaired participant within an impairment group; however, participants with normal renal function may be matched to 1 participant from more than 1 renal impairment group. Potential participants will be screened to assess their eligibility to enter the study up to 4 weeks prior to administration of study intervention. Eligible participants will be admitted to the study site on Day -1. On Day 1, a "A" single oral dose of AZD0780 will be administered, and participants will be confined to the study site until after assessments are completed on Day 11. For participants with ESRD (Group 2), the first post dose HD session should be scheduled to start 26 hours after administration of AZD0780. Subsequent HD sessions should be scheduled as clinically appropriate. Serial PK (venous) blood samples will be collected up to 240 hours postdose and urine samples will be collected up to 96 hours postdose for the measurement of AZD0780. Urine collection is not required for participants who are anuric (ie, participants with ESRD on HD \[Group 2\]). For participants with ESRD (Group 2), blood samples for PK analysis will also be collected prior to, during, and at the end of HD. The entire dialysate will be collected in separate hourly collections on Day 2 for participants with ESRD (Group 2) for the measurement of AZD0780. The volume of each hourly collection of dialysate from which a sample is taken will be recorded. Physical examinations, 12-lead electrocardiograms, vital sign measurements, and clinical laboratory tests will be performed to assess safety and tolerability.

Conditions

• Renal Impairment

Interventions

Type	Name	Description
DRUG	AZD0780	A single "A" dose of AZD0780 will be administered in the morning on Day 1 under fasted condition. Study intervention will be administered orally with approximately 240 mL of water.

Timeline

• Start date: 2024-08-02
• Primary completion: 2024-12-01
• Completion: 2024-12-01
• First posted: 2024-09-19
• Last updated: 2025-02-20

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study