Hans-Jürgen Stellbrink1, Keikawus Arastéh, Dirk Schürmann, Christoph Stephan, Inge Dierynck, Ilham Smyej, Richard M W Hoetelmans, Carla Truyers, Paul Meyvisch, Bert Jacquemyn, Kris Mariën, Kenneth Simmen, René Verloes. 1. *ICH Study Center, Hamburg, Germany; †EPIMED, Vivantes Auguste-Viktoria Klinikum, Berlin, Germany; ‡Department of Infectious Diseases and Pulmonary Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany; §Goethe-University Hospital/Medical Center-Infectious Diseases-Unit, Frankfurt, Germany; ‖Research and Early Development Department, Janssen Infectious Diseases BVBA, Beerse, Belgium; ¶Department of General Practice, Katholieke Universiteit Leuven, Leuven, Belgium; and #Department of Infectious Diseases, Janssen Research & Development, High Wycombe, Buckinghamshire, United Kingdom.
Abstract
OBJECTIVES:TMC310911 is a novel HIV type-1 (HIV-1) protease inhibitor with broad in vitro antiviral activity. In this phase 2a, open-label randomized study, the antiviral activity, pharmacokinetics, and safety and tolerability of ritonavir-boostedTMC310911 was assessed. METHODS: In this study, treatment-naive HIV-1 patients (aged 18-60 years) received 1 of the 4 dosing regimens of TMC310911: 150 mg twice-daily (bid) (n = 8), 300 mg bid (n = 8), 75 mg bid (n = 9), or 300 mg once-daily (qd) (n = 8), for 14 days, all coadministered with 100 mg of ritonavir, as only antiretroviral therapy. RESULTS: The mean change from baseline in HIV-1 RNA (log10 copies per milliliter; primary efficacy endpoint) was -1.30 (75 mg bid), -1.14 (150 mg bid), -1.07 (300 mg bid), and -1.06 (300 mg qd) on day 8 and -1.53 (75 mg bid), -1.79 (150 mg bid), -1.69 (300 mg bid), and -1.55 (300 mg qd) on day 15. At steady state (day 14), the mean maximum plasma concentration and mean area under the plasma concentration-time curve from 0 to 12 hours tended to increase dose proportionally for bid doses; TMC310911 daily exposures for the 300 mg qd treatment and 150 mg bid treatment were comparable. The most common (≥ 10%) treatment-emergent adverse events were fatigue (27.3%) and nausea (12.1%); no deaths or serious treatment-emergent adverse events were reported in this study. CONCLUSIONS: Combination treatment with TMC310911 andritonavir showed potent antiviral activity (>1.5 log10 copies/mL decrease in plasma HIV-1 RNA) at all evaluated doses, and treatment was generally safe and well tolerated.
RCT Entities:
OBJECTIVES:TMC310911 is a novel HIV type-1 (HIV-1) protease inhibitor with broad in vitro antiviral activity. In this phase 2a, open-label randomized study, the antiviral activity, pharmacokinetics, and safety and tolerability of ritonavir-boosted TMC310911 was assessed. METHODS: In this study, treatment-naive HIV-1patients (aged 18-60 years) received 1 of the 4 dosing regimens of TMC310911: 150 mg twice-daily (bid) (n = 8), 300 mg bid (n = 8), 75 mg bid (n = 9), or 300 mg once-daily (qd) (n = 8), for 14 days, all coadministered with 100 mg of ritonavir, as only antiretroviral therapy. RESULTS: The mean change from baseline in HIV-1 RNA (log10 copies per milliliter; primary efficacy endpoint) was -1.30 (75 mg bid), -1.14 (150 mg bid), -1.07 (300 mg bid), and -1.06 (300 mg qd) on day 8 and -1.53 (75 mg bid), -1.79 (150 mg bid), -1.69 (300 mg bid), and -1.55 (300 mg qd) on day 15. At steady state (day 14), the mean maximum plasma concentration and mean area under the plasma concentration-time curve from 0 to 12 hours tended to increase dose proportionally for bid doses; TMC310911 daily exposures for the 300 mg qd treatment and 150 mg bid treatment were comparable. The most common (≥ 10%) treatment-emergent adverse events were fatigue (27.3%) and nausea (12.1%); no deaths or serious treatment-emergent adverse events were reported in this study. CONCLUSIONS: Combination treatment with TMC310911 and ritonavir showed potent antiviral activity (>1.5 log10 copies/mL decrease in plasma HIV-1 RNA) at all evaluated doses, and treatment was generally safe and well tolerated.