Pharmacokinetics and Safety of the Experimental, Oral HCV Protease Inhibitor SCH 503034 in Healthy Subjects

Schering Plough’s experimental compound SCH 503034 is an orally active hepatitis C virus NS3 serine protease inhibitor. In the laboratory and in early clinical studies, the drug has shown potent anti-HCV activity.

At the 56^th AASLD meeting in San Francisco (November 11-15, 2005), researchers reported results of a Phase I study that evaluated the pharmacokinetics (PK) and safety of SCH 503034 oral capsules in HCV negative volunteers.

Healthy (HIV negative) participants in this randomized, double-blind study, healthy subjects were randomized 2:1 to receive, SCH 503034 oral capsules, (n=6/group ) 50 mg, 100 mg, 200 mg, 400 mg, 600 mg, 800 mg or placebo (n=3/group).

Plasma samples were collected at multiple time points to 120h post-dose. Pharmacokinetics were analyzed using model independent methods. Safety was assessed by clinical laboratory tests, vital signs, ECGs, physical exams, and occurrence of adverse events.

Results

• Fifty-four subjects completed the study, 36 received SCH 503034, 18 received placebo.
• SCH 503034 was rapidly absorbed following oral administration of capsules (mean Tmax :1-2.25 h across the 6 dosing levels).
• After attaining Tmax, plasma SCH503034 concentrations declined in a bi-phasic manner, with a mean terminal phase half-life (T1/2) of 7.0 to 15 h.
•  Cmax and AUC increased in a dose-related manner.
• The safety profiles were similar in subjects receiving SCH 503034 and placebo.

The study authors conclude, “SCH 503034 was readily bioavailable when administered as a single dose in an oral capsule formulation and was well tolerated in subjects receiving up to 800 mg orally.”

Discussion

These findings are encouraging, as they demonstrate that this novel new compound has excellent bioavailability, is orally administered and demonstrates a favorable safety profile.

11/14/05

Reference
J Zhang and others. Single Dose Pharmacokinetics of a Novel Hepatitis C Protease Inhibitor, SCH 503034, in an Oral Capsule Formulation. Abstract  66787. 56^th annual meeting of the American Association for the Study of Liver Diseases (56^th AASLD). November 11-15, 2005. San Francisco, CA.