Phase 1a – Single Dose Study of Safety, Tolerability and PK of TXL™ in Healthy Volunteers
The TXL™ Phase 1a clinical study was a randomized, blinded, dose-escalation trial to evaluate safety, tolerability and pharmacokinetics. Healthy volunteers received a single dose ranging from 25 mg to 400 mg of TXL™ or a standard dose of Viread® for comparison of intracellular levels of the active antiviral, tenofovir diphosphate (“TFV-PP”).
TXL™ was well tolerated and there were no laboratory, vital sign, electrocardiogram changes or adverse event trends attributable to drug. In addition, plasma concentrations of TXL™ increased linearly with dose and target plasma levels were attained. The active antiviral, TFV-PP, was measurable in peripheral blood mononuclear cells (“PBMC”) from all patients after a single 400 mg dose of TXL™.
PBMC levels of TFV-PP remained detectable for six days after the single 400 mg dose of TXL™, suggesting the possibility of a convenient, once-weekly dosing regimen.
Phase 1b – Multiple Dose Study of Safety, Tolerability and PK of TXL™ in Healthy Volunteers
Data from the Phase 1b study demonstrate that TXL™ was safe and well tolerated by healthy volunteers in all five dosing groups, receiving up to 100 mg orally per day. In addition to demonstrating an excellent safety profile in volunteers, plasma levels of TXL™ and tenofovir showed a favorable, dose-dependent pharmacokinetic profile.
Consistent with the liver-targeted character of this prodrug, TXL™ rapidly disappeared from the circulation, with a half-life ranging from 1-2 hours, while plasma tenofovir levels remained low. There was no evidence of accumulation of either TXL™ or tenofovir in this 14-day study.
These pharmacokinetic results are consistent with the anticipated improved safety profile of TXL™ compared to tenofovir disoproxil fumarate (TDF, Gilead’s Viread®).
Phase 2a – Multiple Ascending Dose Proof of Concept Study
ContraVir is developing TXL™ for Hepatitis B in Phase 2 clinical studies.