AASLD 2013:28天的泰诺福韦富马酸Alafenamide （ TAF）的安全性和有

StephenW

二十八富马酸天的泰诺福韦Alafenamide （ TAF）的安全性和有效性
TITLE: Twenty Eight Day Safety and Efficacy of Tenofovir Alafenamide (TAF) Fumarate in Chronic Hepatitis B (CHB) Patients
AUTHORS (FIRST NAME, LAST NAME): Kosh Agarwal1, Scott K. Fung2, Tuan T. Nguyen3, Wendy Cheng4, Eric Sicard5, Stephen D. Ryder6, John F. Flaherty7, Eileen Lawson7, Sally Zhao7, Mani Subramanian7, John G. McHutchison7, Edward J. Gane8, Graham R. Foster9
Institutional Author(s):
INSTITUTIONS (ALL): 1. Institute of Liver Studies, Kings College Hospital, London, United Kingdom.
2. Toronto General Hospital, Toronto, ON, Canada.
3. T Nguyen Research and Education, San Diego, CA, United States.
4. Royal Perth Hospital, Perth, WA, Australia.
5. Algorithme Pharma, Montreal, QC, Canada.
6. Nottingham University Hospitals NHS Trust and Biomedical Research Unit, Nottingham, United Kingdom.
7. Gilead Sciences, Foster City, CA, United States.
8. Auckland Clinical Studies, Auckland, New Zealand.
9. Queen Mary’s University of London, Barts Health, London, United Kingdom.
ABSTRACT BODY: Background: TAF, an alternate prodrug of tenofovir (TFV), is stable in plasma and more efficiently delivers TFV into lymphoid cells and hepatocytes at lower systemic TFV exposures than tenofovir DF (TDF). In ongoing Phase 2 studies in HIV infection when combined with other antiretrovirals, TAF demonstrated similar efficacy to TDF with less impact on renal function and bone mineral density.
Methods: Prospective, randomized (1:1:1:1:1), open-label, Phase 1b study. CHB subjects with HBV DNA ≥2 x 103 IU/mL and ALT ≤10 x ULN received treatment with TAF at doses of 8, 25, 40, and 120 mg, or TDF 300 mg for 28 days with 4 weeks off-treatment follow-up. Intensive pharmacokinetics (PK) were performed on Day 1.
Results: 51 subjects were enrolled and completed 28 days of dosing. Groups were well matched at baseline (table) and subjects were mostly male and either Asian or Black; 53% were HBeAg-negative. No subject experienced a serious adverse event (SAE), grade 3/4 AE, or discontinued for AE. No subject experienced a renal event (≥0.5 mg/dL increase in creatinine from baseline, phosphorus <2 mg/dL, or CrCL <50 mL/min). The kinetics of reduction in serum HBV DNA were similar across all TAF dose groups and comparable to TDF. PK analysis suggested mean reductions in TFV exposures (AUCinf) of 97%, 93%, 81%, and 32% at TAF doses of 8, 25, 40, and 120 mg, respectively, relative to the mean TFV exposure with TDF.
Conclusions: Over 28 days, TAF was safe and well tolerated. Declines in HBV DNA with TAF did not differ by dose and were similar to TDF. Additionally, TAF may have less impact on renal function (CrCL) compared to TDF. Further clinical trials with TAF are warranted in CHB patients.

咬牙硬挺

感谢分享