ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1224

Prednisone Has No Effect On Odanacatib Pharmacokinetics In Healthy Subjects

Gene Marcantonio1, Chengcheng Liu2, Stefan Zajic3, Chantal Mahon2, David Hreniuk2, Anish Mehta4, Kate Mostoller2, Denise Morris5, Hongwei Xue5 and S. Aubrey Stoch2, 1Merck & Co., Whitehouse Station, NJ, 2Merck Sharp & Dohme Corp., Whitehouse Station, NJ, 3Merck Sharp & Dohme Corp, Whitehouse Station, NJ, 4Merck Sharp & Dohme Corp.,, Whitehouse Station, NJ, 5Covance, Madison, WI

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: , , , ,

Session Information

Title: Osteoporosis and Metabolic Bone Disease: Clinical Aspects and Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose: We evaluated the effect of prednisone, a glucocorticoid believed to induce the CYP P450 enzyme, on the pharmacokinetics of odanacatib, a novel Cathepsin K inhibitor that is in development for the treatment of osteoporosis. 

Methods:

This was an open-label, 2-period crossover study in healthy male subjects.  In Period 1, midazolam 2 mg was administered on Day -1 followed by a single oral dose of odanacatib 50 mg on Day 1.  There were at least 14 days from the last pharmacokinetic sampling on Day 15 of Period 1 to the Day 1 dosing in Period 2.  In Period 2, subjects were administered a single oral dose of prednisone 10 mg qd on Days 1 through 28.  On Day 14 of Period 2, subjects were co-administered prednisone 10 mg and odanacatib 50 mg.  On days 1 and 28 of Period 2, subjects were co-administered prednisone 10 mg and midazolam 2 mg.  On Days 42 and 56 of Period 2, subjects were administered a single oral dose of midazolam 2 mg.  The plasma pharmacokinetic parameters (AUC0-∞, Cmax, Tmax, and apparent terminal t½) were assessed based on blood samples that were collected at predose and various time points through 336 hours following odanacatib administration on Day 1/Period 1, as well as predose on Day 1, predose on Day 14, and various time points through 336 hours following odanacatib administration on Day 14/Period 2.  Safety and tolerability were assessed by physical examination, evaluation of vital signs and electrocardiogram (ECG) measurements, and monitoring adverse experiences (AE) throughout the study.

Results: There were 15 subjects enrolled.  Mean age was 31 years and a mean BMI was 25.8.  The odanacatib AUC0-∞ GMR (90% CI) [odanacatib + prednisone/odanacatib alone] was 1.06 (0.96, 1.17).  The estimated Cmax GMR (90% CI) was 0.96 (0.84, 1.10). The median Tmax value remained 4 hours for odanacatib alone and with co-administration of prednisone and the harmonic mean (jack-knife standard deviation) for apparent terminal t½was 74.6 (17.9) for odanacatib alone and 66.8 (25.1) for odanacatib + prednisone .   There were no serious AEs or AEs leading to discontinuation.

Conclusion: Prednisone had no effect on odanacatib pharmacokinetics when co-administered with odanacatib.

Disclosure:

G. Marcantonio,

Merck Sharp Dohme Corp.,

3,

Merck Sharp Dohme Corp,

1;

C. Liu,

Merck Sharp Dohme Corp,

3;

S. Zajic,

Merck Pharmaceuticals,

1,

Merck Pharmaceuticals,

3;

C. Mahon,

Merck Sharp Dohme Corp,

1,

Merck Sharp Dohme Corp,

3;

D. Hreniuk,

Merck Human Health,

3,

Merck Human Health,

3;

A. Mehta,

Merck Sharp Dohme Corp.,

1,

Merck Human Health,

3;

K. Mostoller,

Merck Sharp Dohme Corp.,

3;

D. Morris,

Covance,

5;

H. Xue,
None;

S. A. Stoch,

Merck Sharp Dohme Corp,

1,

Merck Sharp Dohme Corp,

3.

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