NCT05359627

A Pharmacokinetic Study of Polymyxin B in Healthy Subjects and Subjects With Renal Insufficiency

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 22 (actual)
• Sponsor: TTY Biopharm · Industry
• Sex: All
• Age: 20 Years – 70 Years
• Healthy volunteers: Accepted

Summary

This is an open-label, single-center, single-dose, parallel-group study to evaluate the PK and safety profiles of polymyxin B administered by IV infusion in healthy subjects and subjects with renal insufficiency.

Detailed description

The study will enroll approximately 24 adult subjects in the following three Arms based on renal function. Approximately 8 subjects for each Arm are planned to be enrolled to fulfill the analysis of at least 6 evaluable subjects in each Arm. The subject who drops out of the study may be replaced at the discretion of the Sponsor. * Arm 1 (normal renal function group): Subjects with CLcr ≥ 90 mL/min * Arm 2 (mild renal insufficiency group): Subjects with CLcr between 60 and 89 mL/min (inclusive) * Arm 3 (long-term IHD group): Subjects with ESRD receiving IHD therapy 3 times a week for at least 3 months prior to dosing of study drug; Subjects will receive a single dose of polymyxin B one day after his/her 3rd dialysis of the week.

Conditions

• Antibiotic Toxicity

Interventions

Type	Name	Description
DRUG	Polymyxin B	Polymyxin B acts against gram-negative bacteria (GNB) only, via three known mechanisms of action: First, polymyxin B can electrostatically interact with the outer membranes of GNB to compete against and displace calcium and magnesium divalent cations from membrane lipids, thereby disrupting lipopolysaccharide (LPS) molecules on the outer membrane and triggering their release. This leads to changes in the permeability of the bacterial membrane and subsequently causes cell content leakage, cell lysis, and death. Second, polymyxin B can act as a surfactant, as it is amphipathic and contains both lipophilic and lipophobic groups; this allows it to penetrate cell membranes, interact with the phospholipids within, and rapidly disrupt membranes to kill bacteria. Third, polymyxin B can bind to the lipid A portion of bacterial endotoxin or LPS molecules, thus neutralizing their toxicity.

Timeline

• Start date: 2022-07-26
• Primary completion: 2023-03-03
• Completion: 2023-03-03
• First posted: 2022-05-04
• Last updated: 2023-04-27

Locations

1 site across 1 country: Taiwan