Safety and Tolerability of Odanacatib (0822-059)
- Registration Number
- NCT01068262
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 44
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Panel B - Odanacatib Odanacatib Panel B - Healthy female subjects receiving Odanacatib Panel A - Odanacatib Odanacatib Panel A - Healthy male subjects receiving Odanacatib
- Primary Outcome Measures
Name Time Method 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 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
Name Time Method Overall Maximum Concentration (Cmax) of Odanacatib in Healthy Male and Postmenopausal Female Participants at Week 4 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.
Number of Participants Who Discontinued Study Treatment Due to an AE 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.
Apparent Terminal Half-Life (t1/2) of Odanacatib in Healthy Male and Postmenopausal Female Participants at Week 4 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.
Area Under the Curve of Plasma Concentration-time From 0 to 168 Hours (AUC0-168hr) of Odanacatib at Week 4 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.
Concentration of Odanacatib at 168 Hours (C168hr) in Healthy Male and Postmenopausal Female Participants at Week 4 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.
Overall Time to Maximum Concentration (Tmax) of Odanacatib in Healthy Male and Postmenopausal Female Participants at Week 4 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.
Number of Participants With At Least One Adverse Event (AE) in the Baseline, Treatment, or Post-Treatment Periods 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.