Dosing Study of SCH 417690, New CCR5 Receptor Antagonist from Schering-Plough

In this multi-center study, researchers evaluated the safety, tolerability, pharmacokinetics, and antiviral activity of SCH 417690 monotherapy administered to HIV subjects.

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+ counts > 200 cells/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 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.

Based on these findings, the authors conclude, “SCH 417690 demonstrated potent antiviral activity against CCR5-using HIV-1 strains at all doses studied. These findings, along with the marked post-antiviral effectthat lasted a number of days after completion of dosing, support further clinical development of SCH 417690.”

Phase 3 studies of SCH417690 are expected to begin enrolling by the Fall of 2005.

Charatie Hospital, Berlin, Germany, CentreCap, Montpellier, France, University of Cologne, Cologne, Germany, Biotrial/University Hospital, Nantes and Rennes, France, University of Kiel, Kiel, Germany, Schering Plough Research Institute, Kenilworth, New Jersey, USA.

07/27/05

Reference
D Schuermann and others. SCH 417690: Antiviral Activity of a Potent New CCR5 Receptor Antagonist. Abstract TuOa0205 (oral). 3^rd IAS Conference on HIV Pathogenesis and Treatment. July 24-27, 2005. Rio de Janeiro, Brazil.