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-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 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.
*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.
Correspondence to: René Verloes, MD, Janssen Infectious Diseases, Turnhoutseweg 30, Beerse B2340, Belgium (e-mail: firstname.lastname@example.org).
Supported by Janssen Research & Development, Ireland (previously known as Tibotec Pharmaceuticals Ltd.). Sponsor also provided formal review of manuscript.
H-J.S., K.A., D.S., and C.S. were investigators for this study. H-J.S. is the Director of the ICH Study Center, Hamburg, Germany, and has been an advisory board member and consultant for Abbott, Gilead Sciences, ViiV Healthcare, Boehringer Ingelheim, Merck Sharp & Dohme, Janssen-Cilag and Bristol-Myers Squibb; K.A. is the CEO of EPIMED and Director of the Clinic for Internal Medicine in the Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany. D.S. is an employee of Charité-Universitätsmedizin Berlin, Germany. C.S. is Internal Medicine/Infectious Diseases Consultant at Goethe-University Hospital/Medical Center-Infectious Diseases-Unit, Frankfurt, Germany; he has received travel grants and speaker's honoraria from Janssen Research and Development LLC, Ireland. I.D., I.S., R.M.W.H., C.T., P.M., B.J., K.M., K.S., and R.V. are employees of Janssen Research & Development.
H-J.S., K.A., D.S., and C.S. were investigators for this study and were involved in study conduct. I.D., R.M.W.H., I.S., K.S., and R.V. were involved in study design; R.M.W.H. was also involved in interpretation of data; K.M. was involved in the study conduct; B.J. was the project leader and P.M. and C.T. were involved in analysis and interpretation of the data. All authors met International Committee of Medical Journal Editors criteria and all those who fulfilled those criteria are listed as authors. All authors approved submission to the journal.
The study is registered at ClinicalTrials.gov (NCT00838162).
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Received June 19, 2013
Accepted September 09, 2013