Single-Dose Study to Evaluate the PKs of Pretomanid in Subjects With Renal Impairment Compared to Subjects With Normal Renal Function

Tuberculosis Clinical Trial

Official title: A Phase I, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics and Safety of Pretomanid in Subjects With Renal Impairment Compared to Subjects With Normal Renal Function

Status Not yet recruiting

Clinical Trial Summary

This is a Phase I, open-label, single dose, sequential group study to compare the safety and pharmacokinetics of pretomanid in the following groups of subjects: 1) subjects with severe renal impairment including those with End Stage Renal Disease (ESRD) not needing dialysis, and subjects with mild or moderate renal impairment, designated as Groups 2, 3, and 4, respectively; and 2) subjects with normal renal function matched to the above renal impairment groups, designated as Groups 1A, 1B, and 1C, respectively.

The study will be conducted following a reduced Pharmacokinetic (PK) study design in Part A and Part B. Part A will enroll subjects from Group 1A (i.e., 6 healthy matched controls) and Group 2 (i.e., 6 subjects with severe renal impairment and ESRD, not on dialysis). A decision will be made after the PK of pretomanid and safety of subjects enrolled in Part A have been reviewed. If Part A demonstrated different pretomanid exposures at least a 50-100% increase in Area under the Curve (AUC) in Group 2 (severe renal impairments and ESRD, not on dialysis) relative to the exposures in Group 1A (matched subjects with normal renal function), then the reduced PK study will extend to the full PK study to enroll subjects into Part B (i.e., to investigate mild, and moderate renal impairment) and all enrollment will be initiated concurrently in Part B groups (1B, 1C, 3 and 4). If no difference in PK and safety is observed in Part A, then no further study (Part B) is recommended

The approximate patient involvement will be 3 months. The primary objective is to evaluate the PK profiles of pretomanid in plasma and urine after a single oral dose of 200 mg in subjects with renal impairment compared to matched healthy controls.

Clinical Trial Description

This is a Phase I, open-label, single dose, sequential group study to compare the safety and pharmacokinetics of pretomanid in the following groups of subjects: 1) subjects with severe renal impairment including those with End Stage Renal Disease (ESRD) not needing dialysis, and subjects with mild or moderate renal impairment, designated as Groups 2, 3, and 4, respectively; and 2) subjects with normal renal function matched to the above renal impairment groups, designated as Groups 1A, 1B, and 1C, respectively.

The study will be conducted following a reduced Pharmacokinetic (PK) study design in Part A and Part B. Part A will enroll subjects from Group 1A (i.e., 6 healthy matched controls) and Group 2 (i.e., 6 subjects with severe renal impairment and ESRD, not on dialysis). A decision will be made after the PK of pretomanid and safety of subjects enrolled in Part A have been reviewed. If Part A demonstrated different pretomanid exposures at least a 50-100% increase in Area under the Curve (AUC) in Group 2 (severe renal impairments and ESRD, not on dialysis) relative to the exposures in Group 1A (matched subjects with normal renal function), then the reduced PK study will extend to the full PK study to enroll subjects into Part B (i.e., to investigate mild, and moderate renal impairment) and all enrollment will be initiated concurrently in Part B groups (1B, 1C, 3 and 4). If no difference in PK and safety is observed in Part A, then no further study (Part B) is recommended

The approximate patient involvement will be 3 months. The primary objective is to evaluate the PK profiles of pretomanid in plasma and urine after a single oral dose of 200 mg in subjects with renal impairment compared to matched healthy controls. The secondary objectives are 1) to assess the safety profile of a single oral dose of 200 mg pretomanid in renally impaired subjects to matched healthy controls; and 2) to evaluate the PK profiles or representative pretomanid metabolites (M19 and M50) in plasma and urine. ;

Related Conditions & MeSH terms

• Renal Impairment
• Renal Insufficiency
• Tuberculosis

• NCT number: NCT03896750
• Study type: Interventional
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: December 7, 2023
• Completion date: July 14, 2025