Safety and Tolerability of Odanacatib (0822-059)

Merck Sharp & Dohme LLC44 enrolled

Overview

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Osteoporosis

Interventions

OdanacatibDRUG

Oral doses of Odanacatib 50 mg administered once weekly for 4 consecutive weeks

Comparator: PlaceboDRUG

Oral Placebo tablet administered once weekly for 4 consecutive weeks

Eligibility

Sex: ALLMin age: 45 YearsMax age: 75 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

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.

Time frame: Baseline to Week 4

Secondary Outcomes

Area Under the Curve of Plasma Concentration-time From 0 to 168 Hours (AUC0-168hr) of Odanacatib at Week 4

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.

Time frame: Baseline, Week 4 (1, 2, 6, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours post-dose)

Overall Maximum Concentration (Cmax) of Odanacatib in Healthy Male and Postmenopausal Female Participants at Week 4

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.

Time frame: Baseline, Week 4 (1, 2, 6, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours post-dose)

Concentration of Odanacatib at 168 Hours (C168hr) in Healthy Male and Postmenopausal Female Participants at Week 4

Data from ClinicalTrials.gov

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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.

Time frame: Week 4 (168 hours postdose)

Overall Time to Maximum Concentration (Tmax) of Odanacatib in Healthy Male and Postmenopausal Female Participants at Week 4

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.

Time frame: Baseline, Week 4 (1, 2, 6, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours post-dose)

Apparent Terminal Half-Life (t1/2) of Odanacatib in Healthy Male and Postmenopausal Female Participants at Week 4

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.

Time frame: Baseline, Week 4 (1, 2, 6, 12, 24, 48, 72, 96, 120, 144, 168, 240, and 336 hours post-dose)

Number of Participants With At Least One Adverse Event (AE) in the Baseline, Treatment, or Post-Treatment Periods

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.

Time frame: Up to Day 58

Number of Participants Who Discontinued Study Treatment Due to an AE

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.

Time frame: Up to Week 4