Safety, Pharmacokinetics, and Pharmacodynamics of ASP 3662, a Novel 11β‐Hydroxysteroid Dehydrogenase Type 1 Inhibitor, in Healthy Young and Elderly Subjects

Inhibition of the enzyme 11 β ‐hydroxysteroid dehydrogenase type 1 (11β‐ HSD 1) represents a potential mechanism for improving pain conditions. ASP 3662 is a potent and selective inhibitor of 11β‐ HSD 1. Two phase I clinical studies were conducted to assess the safety, tolerability, pharmacokinetics ( PK s), and pharmacodynamics (PDs) of single and multiple ascending doses of ASP 3662 in healthy young and elderly non‐Japanese and young Japanese subjects. Nonlinear, more than dose‐proportional PK s were observed for ASP 3662 after single‐dose administration, particularly at lower doses (≤ 6 mg); the PK s at steady state were dose proportional, although the time to ASP 3662 steady state was dose dependent at lower doses (≤ 2 mg). Similar PK s were observed among young Japanese, young non‐Japanese, and elderly non‐Japanese subjects. Specific inhibition of 11β‐ HSD 1 occurred after both single and multiple doses of ASP 3662. A marked dissociation between PKs and PDs was observed after single but not multiple doses of ASP 3662. ASP 3662 was generally safe and well tolerated.