Safety and Tolerability of Odanacatib (0822-059)

• ClinicalTrials.gov Identifier: NCT01068262
• Recruitment Status: Completed
• First Posted: February 12, 2010
• Results First Posted: June 16, 2017
• Last Update Posted: August 28, 2018
• Sponsor: Merck Sharp & Dohme Corp.
• Information provided by (Responsible Party): Merck Sharp & Dohme Corp.

Study Description

Brief Summary:

This study will test the weighted average inhibition of u-NTx/Cre (aminoterminal crosslinked telopeptide of Type 1 collagen) and AUC (0-168 hours) of Odanacatib

Condition or disease	Intervention/treatment	Phase
Osteoporosis	Drug: Odanacatib; Drug: Comparator: Placebo	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 44 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Odanacatib (MK0822) in Healthy Male and Postmenopausal Female Subjects
• Actual Study Start Date: December 8, 2009
• Actual Primary Completion Date: April 26, 2010
• Actual Study Completion Date: May 2, 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: Panel A - Odanacatib; Panel A - Healthy male subjects receiving Odanacatib	Drug: Odanacatib; Oral doses of Odanacatib 50 mg administered once weekly for 4 consecutive weeks; Other Name: MK0822
Placebo Comparator: Panel A - Placebo; Panel A - Healthy male subjects receiving placebo	Drug: Comparator: Placebo; Oral Placebo tablet administered once weekly for 4 consecutive weeks
Experimental: Panel B - Odanacatib; Panel B - Healthy female subjects receiving Odanacatib	Drug: Odanacatib; Oral doses of Odanacatib 50 mg administered once weekly for 4 consecutive weeks; Other Name: MK0822
Placebo Comparator: Panel B - Placebo; Panel B - Healthy female subjects receiving placebo	Drug: Comparator: Placebo; Oral Placebo tablet administered once weekly for 4 consecutive weeks

Outcome Measures

Primary Outcome Measures :

1. Weighted Average Inhibition (WAI) of Urine Aminoterminal Crosslinked Telopeptide of Type I Collagen (u-NTx/Cr) After Administration of Odanacatib 50 mg or Placebo Qw for 4 Weeks in Healthy Males and Postmenopausal Females [ Time Frame: Baseline to Week 4 ]
   uNTx/Cr is a biomarker of bone resorption. Urine samples were obtained predose on Day 1 (Baseline) and at various timepoints up to 336 hr postdose on Day 22 (Week 4). Fold change from baseline in time weighted average (TWA) of uNTx/Cr on log scale was analyzed via a linear mixed effect model. All analyses were carried out on the log-fold scale and final results were reported on the original percent scale in WAI after back transformation. The conversion used was weighted average inhibition (WAI) = (1-exp [mean])*100, where the mean was the least squares (LS) mean of log-transformed ratio (TWA/baseline) from the above model.

Secondary Outcome Measures :

1. Area Under the Curve of Plasma Concentration-time From 0 to 168 Hours (AUC0-168hr) of Odanacatib at Week 4 [ Time Frame: Baseline, Week 4 (1, 2, 6, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours post-dose) ]
   Blood samples were obtained predose on Day 1 (Baseline) and at various timepoints up to 336 hr postdose on Day 22 (Week 4) to determine the similarity of steady-state AUC0-168 hr of odanacatib 50 mg administered Qw for 4 weeks in healthy males and postmenopausal females. Characterization of AUC0-168hr after administration of the final, Qw dose of Odanacatib 50 mg at steady state is reflective of the clinical dosing interval.
2. Overall Maximum Concentration (Cmax) of Odanacatib in Healthy Male and Postmenopausal Female Participants at Week 4 [ Time Frame: Baseline, Week 4 (1, 2, 6, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours post-dose) ]
   Blood samples were obtained predose on Day 1 (Baseline) and at various timepoints up to 336 hr postdose on Day 22 (Week 4) to determine the similarity of steady-state Cmax of odanacatib 50 mg administered Qw for 4 weeks in healthy males and postmenopausal females.
3. Concentration of Odanacatib at 168 Hours (C168hr) in Healthy Male and Postmenopausal Female Participants at Week 4 [ Time Frame: Week 4 (168 hours postdose) ]
   Blood samples were obtained at 168 hours postdose on Day 22 (Week 4) to determine the similarity of steady-state C168hr (trough concentrations) of odanacatib 50 mg administered Qw for 4 weeks in healthy males and postmenopausal females.
4. Overall Time to Maximum Concentration (Tmax) of Odanacatib in Healthy Male and Postmenopausal Female Participants at Week 4 [ Time Frame: Baseline, Week 4 (1, 2, 6, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours post-dose) ]
   Blood samples were obtained predose on Day 1 (Baseline) and at various timepoints up to 336 hr postdose on Day 22 (Week 4) to determine the similarity of steady-state Tmax of odanacatib 50 mg administered Qw for 4 weeks in healthy males and postmenopausal females.
5. Apparent Terminal Half-Life (t1/2) of Odanacatib in Healthy Male and Postmenopausal Female Participants at Week 4 [ Time Frame: Baseline, Week 4 (1, 2, 6, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours post-dose) ]
   Blood samples were obtained predose on Day 1 (Baseline) and at various timepoints up to 336 hr postdose on Day 22 (Week 4) to determine the similarity of the apparent t1/2 of odanacatib 50 mg administered Qw for 4 weeks in healthy males and postmenopausal females. Harmonic mean, jack-knife standard deviation reported for apparent terminal t1/2.
6. Number of Participants With At Least One Adverse Event (AE) in the Baseline, Treatment, or Post-Treatment Periods [ Time Frame: Up to Day 58 ]
   An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the SPONSOR's product, is also an AE. The study determined if the number of AEs experienced by participants receiving Odanacatib 50 mg Qw for 4 consecutive weeks was sufficiently low to permit continued clinical investigation. In addition to AEs during the treatment period and post-treatment follow-up period, AEs may have occurred prior to treatment in screened participants as a result of urine and blood sampling at Baseline.
7. Number of Participants Who Discontinued Study Treatment Due to an AE [ Time Frame: Up to Week 4 ]
   An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the SPONSOR's product, whether or not considered related to the use of the product. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition which is temporally associated with the use of the SPONSOR's product, is also an AE. The study determined if the number of participants who discontinued treatment with Odanacatib 50 mg Qw for 4 consecutive weeks due to AEs was sufficiently low to permit continued clinical investigation.

Eligibility Criteria

• Ages Eligible for Study: 45 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• male subject between the ages of 50 and 75 years; post menopausal female subjects between the ages of 45 and 75 years
• Subject is in good general health
• Subject has no evidence of metabolic bone disorder other than osteopenia or osteoporosis
• Subject is a non-smoker

Exclusion Criteria:

• Subject works night shift and is unable to avoid nightshift work during the study
• Subject has had major surgery, donated blood or participated in another investigational study with in the past 4 weeks
• Subject has a history of stroke, chronic seizures, or major neurological disease
• Subject has a history of cancer
• Subject consumes excessive amounts of alcohol or caffeine

Contacts and Locations

Sponsors and Collaborators

Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Monitor; Merck Sharp & Dohme Corp.

More Information

Publications of Results:

Anderson MS, Gendrano IN, Liu C, Jeffers S, Mahon C, Mehta A, Mostoller K, Zajic S, Morris D, Lee J, Stoch SA. Odanacatib, a selective cathepsin K inhibitor, demonstrates comparable pharmacodynamics and pharmacokinetics in older men and postmenopausal women. J Clin Endocrinol Metab. 2014 Feb;99(2):552-60. doi: 10.1210/jc.2013-1688. Epub 2013 Nov 25.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT01068262
• Other Study ID Numbers: 0822-059; 2010_508 ( Other Identifier: Merck ); MK-0822-059
• First Posted: February 12, 2010
• Results First Posted: June 16, 2017
• Last Update Posted: August 28, 2018
• Last Verified: July 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

Additional relevant MeSH terms:

Osteoporosis; Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases