3rd International AIDS Society Conference on HIV Pathogenesis and Treatment Rio de Janeiro - July 24 - 27, 2005

SCH 417690: ANTIVIRAL ACTIVITY OF A POTENT NEW CCR5 RECEPTOR ANTAGONIST

IAS Conf HIV Pathog Treat 2005 Jul 24-27;3rd: Abstract No. TuOa0205

Schuermann D.¹, Pechardscheck C.¹, Rouzier R.², Nougarede R.², Faetkenheuer G.³, Ochlast I.³, Raffi F.⁴, Hoffman C.⁵, Greaves W.⁶, Sansone A.^6
1Charatie Hospital, Berlin, Germany, ²CentreCap, Montpellier, France, ³University of Cologne, Cologne, Germany, ⁴Biotrial/University Hospital, Nantes and Rennes, France, ⁵University of Kiel, Kiel, Germany, ⁶Schering Plough Research Institute, Kenilworth, New Jersey, United States of America

INTRODUCTION: This study was designed to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of SCH 417690 monotherapy administered to HIV-infected subjects.

METHODS: Forty eight HIV-infected individuals were enrolled into a sequential rising dose study to evaluate 10 mg, 25 mg and 50 mg BID of SCH 417690 versus placebo for 14 days. Within each of the three cohorts (N = 16), 12 subjects received SCH 417690 and 4 subjects received placebo in a randomized, blinded design. Subjects were either treatment naïve or had had no antiretroviral treatment for a minimum of eight weeks prior to enrollment, had CCR5-tropic virus only, and had CD4+ cell counts ≥200/mm³. All subjects were followed for an additional 14 days after completion of dosing.

RESULTS: SCH 417690 was safe and well tolerated. Analysis of the pharmacokinetic profiles in the three dose levels showed dose proportionality with steady-state Cmin values above SCH 417690's IC90. There was a statistically significant dose-related suppression of HIV RNA across all three dose levels. Mean log₁₀ reductions in HIV RNA were -0.93, -1.49, and -1.62 for the 10 mg BID, 25 mg BID, and 50 mg BID groups, respectively. The 25 and 50 mg BID doses showed a similar maximum antiviral effect that was superior to the 10 mg BID dose. HIV RNA slowly returned toward baseline after completion of dosing. CD4+ counts also improved during treatment.

CONCLUSIONS: SCH 417690 demonstrated potent antiviral activity against CCR5-using HIV-1 strains at all doses studied. These findings, along with the marked post-antiviral effect which lasted a number of days after completion of dosing, support further clinical development of SCH 417690.

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Basic | TuOa0205 | Wayne Greaves
New antiretroviral targets and compounds

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