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dc.contributor.authorAgarwal, Ken_US
dc.contributor.authorFung, SKen_US
dc.contributor.authorNguyen, TTen_US
dc.contributor.authorCheng, Wen_US
dc.contributor.authorSicard, Een_US
dc.contributor.authorRyder, SDen_US
dc.contributor.authorFlaherty, JFen_US
dc.contributor.authorLawson, Een_US
dc.contributor.authorZhao, Sen_US
dc.contributor.authorSubramanian, GMen_US
dc.contributor.authorMcHutchison, JGen_US
dc.contributor.authorGane, EJen_US
dc.contributor.authorFoster, GRen_US
dc.description.abstractBACKGROUND & AIMS: Tenofovir alafenamide, a phosphonate prodrug of tenofovir with greater plasma stability than tenofovir disoproxil fumarate, provides efficient delivery of active drug to hepatocytes at reduced systemic tenofovir exposures. METHODS: Non-cirrhotic, treatment-naïve subjects with chronic hepatitis B were randomized (1:1:1:1:1) to receive tenofovir alafenamide 8, 25, 40, or 120 mg, or tenofovir disoproxil fumarate 300 mg for 28 days and assessed for safety, antiviral response, and pharmacokinetics, followed-up by off-treatment for 4 weeks. RESULTS: 51 subjects were randomized and all completed study treatment. Groups were generally well matched (67% male, 57% Asian, 53% HBeAg-negative, mean HBV DNA approximately 6.0 log10 IU/ml) with HBV genotypes reflective of the population. No subject experienced an adverse event that was serious or severe (grade 3/4). Across the tenofovir alafenamide groups, similar mean changes in serum HBV DNA were found at Week 4 (-2.81, -2.55, -2.19, and -2.76 log10 IU/ml for the 8, 25, 40, and 120 mg groups, respectively) which were also comparable to the control (-2.68 log10 IU/ml for tenofovir disoproxil fumarate 300 mg). Kinetics of viral decline were also similar among groups. Tenofovir alafenamide pharmacokinetics were linear and proportional to the dose; doses⩽25 mg were associated with ⩾92% reductions in mean tenofovir area under the curve relative to tenofovir disoproxil fumarate 300 mg. CONCLUSIONS: Tenofovir alafenamide was safe and well tolerated; declines in HBV DNA were similar to tenofovir disoproxil fumarate at all doses evaluated. Tenofovir alafenamide 25 mg has been selected for further hepatitis B clinical development.en_US
dc.format.extent533 - 540en_US
dc.relation.ispartofJ Hepatolen_US
dc.subjectClinical Trialen_US
dc.subjectViral hepatitisen_US
dc.subjectAntiviral Agentsen_US
dc.subjectDNA, Viralen_US
dc.subjectHepatitis B, Chronicen_US
dc.subjectMiddle Ageden_US
dc.subjectTime Factorsen_US
dc.subjectTreatment Outcomeen_US
dc.subjectYoung Adulten_US
dc.titleTwenty-eight day safety, antiviral activity, and pharmacokinetics of tenofovir alafenamide for treatment of chronic hepatitis B infection.en_US
pubs.notesNot knownen_US

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