Abstract

Objectives: This study was conducted in order to assess the effect of multiple doses of odanacatib, a cathepsin (Cat)-K inhibitor, on the pharmacokinetics of digoxin. Materials: Twelve healthy male and female subjects received 0.5 mg digoxin and 50 mg odanacatib. Methods: This openlabel study was conducted to determine the effect of odanacatib on the plasma pharmacokinetics of immunoreactive digoxin. Subjects received a single oral dose of 0.5 mg digoxin followed by a 10-day washout, followed by 3 once-weekly oral doses of 50 mg odanacatib and co-administration with 0.5 mg digoxin with the last odanacatib dose. A linear mixed-effect model was used to analyze AUC_0–120h. Safety and tolerability were assessed. Results: The estimated geometric-mean-ratio (90% confidence interval) for AUC_0–120h was 0.95 (0.89, 1.01), which was within (0.80, 1.25) determined to demonstrate a lack of interaction. There were no serious AEs, discontinuations due to AEs, or clinically significant abnormalities in ECG or vital sign measurements. Conclusions: This study demonstrated that 50 mg odanacatib did not lead to clinically important effects on the pharmacokinetics of 0.5 mg digoxin.

Author Details

Authors

• S. Aubrey Stoch¹
• Rose Witter¹
• David Hreniuk¹
• Chengcheng Liu¹
• Stefan Zajic¹
• Anish Mehta¹
• Christine Brandquist²
• Cynthia Dempsey²
• Bruce DeGroot²
• Daria Stypinski²
• Andrew Denker¹
• John A. Wagner¹

Departments

• ¹ Merck Sharp & Dohme, Whitehouse Station, NJ, and
• ² Celerion, Lincoln, NE, USA

Address

S. Aubrey Stoch, MD
Clinical Research, Merck Sharp & Dohme Corp.
Rahway, NJ, USA
Email: [email protected]

Citation