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NXL103-Oral Streptogramin: a phase I, double-blind, single escalating oral dose study to evaluate safety, tolerability and pharmacokinetics in healthy adult male volunteers

Abstract number: p1512

Rangaraju  M., Rey  J., Hodgson  J.

Background: 

NXL 103 (formerly XRP 2868) is a novel semi-synthetic oral streptogramin that consists of a 30/70 (w/w ratio) association of a pristinamycin IA (PI) derivative and a pristinamycin IIB (PII) derivative. NXL 103 is being developed for the treatment of respiratory tract and skin and skin structure infections.

Methods: 

60 healthy male subjects were enrolled in this study. 10 subjects in each of 6 cohorts (125 mg, 250 mg, 500 mg, 1000 mg, 1500 mg and 2000 mg) received either NXL103 (8) or placebo (2). An additional cohort of 10 subjects received a single dose of 500 mg NXL103 in fasting and fed conditions. Blood and urine samples for PK analysis were collected at multiple time points. Safety was assessed via adverse events, physical examination, clinical laboratory data, ECG and cardiac monitoring.

Results: 

NXL103 administered as 125 mg capsules at single doses from 125 mg to 2000 mg was well tolerated and safe. There was no serious or severe adverse event, no dose-dependency in the number of AEs or their severity, no significant variation in blood pressure or heart rate, no abnormality on ECG recording, and no clinically significant changes compared to baseline for laboratory parameters. Both components were rapidly absorbed; PI being slightly more rapidly absorbed than PII. The Cmax and AUC (0-t) increased approximately in proportion with dose. The proportion of PI and PII components estimated on mean exposure values was approximately comparable to that administered (30/70), indicating that the relative bioavailabilities of PI and PII are simila. Elimination half-life ranged from between 2 to 3 hours for PI to 4 to 6 hours for PII. Food increased the bioavailability of PI and PII by approximately 20%.

Conclusions: 

NXL103 is safe, well tolerated and exhibits predictable PK properties in healthy volunteers in doses up to 2000 mg administered as a single dose.

Session Details

Date: 01/08/2007
Time: 00:00-00:00
Session name: XXIst ISTH Congress
Subject:
Location: Oxford, UK
Presentation type:
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