Safety and Tolerability of Odanacatib (0822-059)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01068262
• Collaborator: (none)
• Enrollment: 44
• Arms: 4
• Actual Duration (Months): 4.8

Study Details

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
• 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: Dec 8, 2009
• Actual Primary Completion Date: Apr 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 Names: 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 Names: 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 [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 [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 [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 [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 [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 [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 [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 [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

Criteria

• Ages Eligible for Study: 45 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Monitor, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT01068262
• Other Study ID Numbers: 0822-059; 2010_508; MK-0822-059
• First Posted: Feb 12, 2010
• Last Update Posted: Aug 28, 2018
• Last Verified: Jul 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Osteoporosis

Study Results

Participant Flow

Arm/Group Title	Healthy Males: Odanacatib (Panel A)	Healthy Males: Placebo (Panel A)	Healthy Postmenopausal Females: Odanacatib (Panel B)	Healthy Postmenopausal Females: Placebo (Panel B)
Arm/Group Description	Healthy male participants randomized to Odanacatib 50 mg tablet administered once weekly (Qw) for 4 consecutive weeks	Healthy male participants randomized to placebo administered Qw for 4 consecutive weeks.	Healthy postmenopausal female participants randomized to Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks	Healthy postmenopausal female participants randomized to placebo administered Qw for 4 consecutive weeks
Period Title: Overall Study
STARTED	23	9	10	2
COMPLETED	20	8	9	2
NOT COMPLETED	3	1	1	0

Baseline Characteristics

Arm/Group Title	Healthy Males: Odanacatib (Panel A)	Healthy Males: Placebo (Panel A)	Healthy Postmenopausal Females: Odanacatib (Panel B)	Healthy Postmenopausal Females: Placebo (Panel B)	Total
Arm/Group Description	Healthy male participants randomized to Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks	Healthy male participants randomized to placebo administered Qw for 4 consecutive weeks.	Healthy postmenopausal female participants randomized to Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks	Healthy postmenopausal female participants randomized to placebo administered Qw for 4 consecutive weeks	Total of all reporting groups
Overall Participants	23	9	10	2	44
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58.35 (6.11)	56.44 (6.60)	57.50 (7.59)	65.00 (14.14)	58.07 (6.84)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	10 100%	2 100%	12 27.3%
Male	23 100%	9 100%	0 0%	0 0%	32 72.7%

Outcome Measures

1. Primary Outcome

Title	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
Description	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

Outcome Measure Data

Analysis Population Description

The population of male and postmenopausal female participants on Qw treatment with Odanacatib 50 mg for 4 weeks and were compliant with the protocol. The population of male participants on placebo are also included. Postmenopausal females on placebo were not analyzed for WAI due to there being too few participants in this group (N=2).

Arm/Group Title	Odanacatib (MK-0822) in Males (Panel A)	Placebo in Males (Panel A)	Odnacatib (MK-0822) in Postmenopausal Females (Panel B)	Placebo in Postmenopausal Females (Panel B)
Arm/Group Description	Healthy males received oral doses of Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks	Healthy males received oral doses of placebo administered Qw for 4 consecutive weeks	Healthy postmenopausal females received oral doses of Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks	Healthy postmenopausal females received oral doses of placebo administered Qw for 4 consecutive weeks
Measure Participants	20	8	9	0
Least Squares Mean (90% Confidence Interval) [Percent inhibition]	42.8	-26.4	42.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Odanacatib (MK-0822) in Males (Panel A), Placebo in Males (Panel A)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	69.2
	Confidence Interval	(2-Sided) 90%; 50.9 to 80.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Odanacatib (MK-0822) in Males (Panel A), Odnacatib (MK-0822) in Postmenopausal Females (Panel B)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 90%; -14.7 to 14.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The population of male and postmenopausal female participants who received Qw treatment with Odanacatib 50 mg for 4 weeks and were compliant with the protocol.

Arm/Group Title	Odnacatib (MK-0822) in Postmenopausal Females (Panel B)	Odanacatib (MK-0822) in Postmenopausal Females (Panel B)
Arm/Group Description	Healthy postmenopausal females received oral doses of Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks	Healthy postmenopausal females received oral doses of Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks
Measure Participants	20	9
Geometric Mean (95% Confidence Interval) [µM·hr]	33.9	37.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Odanacatib (MK-0822) in Males (Panel A), Placebo in Males (Panel A)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 90%; 0.75 to 1.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The population of male and postmenopausal female participants who received Qw treatment with Odanacatib 50 mg for 4 weeks and were compliant with the protocol.

Arm/Group Title	Odnacatib (MK-0822) in Postmenopausal Females (Panel B)	Odanacatib (MK-0822) in Postmenopausal Females (Panel B)
Arm/Group Description	Healthy postmenopausal females received oral doses of Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks	Healthy postmenopausal females received oral doses of Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks
Measure Participants	20	9
Geometric Mean (95% Confidence Interval) [nM]	379	409

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Odanacatib (MK-0822) in Males (Panel A), Placebo in Males (Panel A)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMR
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 90%; 0.82 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The population of male and postmenopausal female participants who received Qw treatment with Odanacatib 50 mg for 4 weeks and were compliant with the protocol.

Arm/Group Title	Odnacatib (MK-0822) in Postmenopausal Females (Panel B)	Odanacatib (MK-0822) in Postmenopausal Females (Panel B)
Arm/Group Description	Healthy postmenopausal females received oral doses of Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks	Healthy postmenopausal females received oral doses of Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks
Measure Participants	20	9
Geometric Mean (95% Confidence Interval) [nM]	80	85

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Odanacatib (MK-0822) in Males (Panel A), Placebo in Males (Panel A)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Estimate
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 90%; 0.66 to 1.35
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The population of male and postmenopausal female participants who received Qw treatment with Odanacatib 50 mg for 4 weeks and were compliant with the protocol.

Arm/Group Title	Odnacatib (MK-0822) in Postmenopausal Females (Panel B)	Odanacatib (MK-0822) in Postmenopausal Females (Panel B)
Arm/Group Description	Healthy postmenopausal females received oral doses of Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks	Healthy postmenopausal females received oral doses of Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks
Measure Participants	20	9
Median (Full Range) [hr]	4.0	6.0

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The population of male and postmenopausal female participants who received Qw treatment with Odanacatib 50 mg for 4 weeks and were compliant with the protocol.

Arm/Group Title	Odnacatib (MK-0822) in Postmenopausal Females (Panel B)	Odanacatib (MK-0822) in Postmenopausal Females (Panel B)
Arm/Group Description	Healthy postmenopausal females received oral doses of Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks	Healthy postmenopausal females received oral doses of Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks
Measure Participants	20	8
Mean (Standard Deviation) [hr]	89.3 (14.6)	94.7 (20.4)

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

All randomized participants who received ≥1 dose of study treatment

Arm/Group Title	Odanacatib (MK-0822) in Males (Panel A)	Placebo in Males (Panel A)	Odnacatib (MK-0822) in Postmenopausal Females (Panel B)	Postmenopausal Females: Placebo (Panel B)
Arm/Group Description	Healthy males received oral doses of Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks	Healthy males received oral doses of placebo administered Qw for 4 consecutive weeks	Healthy postmenopausal females received oral doses of Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks	Healthy postmenopausal females received oral doses of placebo administered Qw for 4 consecutive weeks
Measure Participants	23	9	10	2
Number [Participants]	8 34.8%	5 55.6%	7 70%	2 100%

8. Secondary Outcome

Title	Number of Participants Who Discontinued Study Treatment Due to an AE
Description	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

Outcome Measure Data

Analysis Population Description

All randomized participants who received ≥1 dose of study treatment

Arm/Group Title	Odanacatib (MK-0822) in Males (Panel A)	Placebo in Males (Panel A)	Odnacatib (MK-0822) in Postmenopausal Females (Panel B)	Placebo in Postmenopausal Females (Panel B)
Arm/Group Description	Healthy males received oral doses of Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks	Healthy males received oral doses of placebo administered Qw for 4 consecutive weeks	Healthy postmenopausal females received oral doses of Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks	Healthy postmenopausal females received oral doses of placebo administered Qw for 4 consecutive weeks
Measure Participants	23	9	10	2
Number [Participants]	2 8.7%	0 0%	1 10%	0 0%

Adverse Events

Arm/Group Title	Healthy Males: Odanacatib 50 mg (Panel A)		Healthy Males: Placebo (Panel A)		Postmenopausal Females: Odanacatib 50 mg (Panel B)		Postmenopausal Females: Placebo (Panel B)
Arm/Group Description	Healthy male participants randomized to Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks		Healthy male participants randomized to placebo administered Qw for 4 consecutive weeks		Healthy postmenopausal female participants randomized to Odanacatib 50 mg tablet administered Qw for 4 consecutive weeks		Healthy postmenopausal female participants randomized to placebo administered Qw for 4 consecutive weeks
All Cause Mortality
	Healthy Males: Odanacatib 50 mg (Panel A)		Healthy Males: Placebo (Panel A)		Postmenopausal Females: Odanacatib 50 mg (Panel B)		Postmenopausal Females: Placebo (Panel B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Healthy Males: Odanacatib 50 mg (Panel A)		Healthy Males: Placebo (Panel A)		Postmenopausal Females: Odanacatib 50 mg (Panel B)		Postmenopausal Females: Placebo (Panel B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/23 (0%)		0/9 (0%)		0/10 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	Healthy Males: Odanacatib 50 mg (Panel A)		Healthy Males: Placebo (Panel A)		Postmenopausal Females: Odanacatib 50 mg (Panel B)		Postmenopausal Females: Placebo (Panel B)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/23 (34.8%)		5/9 (55.6%)		7/10 (70%)		2/2 (100%)
Cardiac disorders
Bundle branch block right	0/23 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/2 (0%)	0
Eye disorders
Dry eye	0/23 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/2 (0%)	0
Gastrointestinal disorders
Abdominal pain	0/23 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/2 (0%)	0
Diarrhoea	1/23 (4.3%)	1	1/9 (11.1%)	1	1/10 (10%)	1	0/2 (0%)	0
Eructation	0/23 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/2 (0%)	0
Gingival pain	0/23 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/2 (0%)	0
Nausea	2/23 (8.7%)	4	0/9 (0%)	0	1/10 (10%)	1	0/2 (0%)	0
Toothache	0/23 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/2 (0%)	0
Vomiting	1/23 (4.3%)	5	0/9 (0%)	0	1/10 (10%)	1	0/2 (0%)	0
General disorders
Chills	1/23 (4.3%)	1	0/9 (0%)	0	1/10 (10%)	1	0/2 (0%)	0
Pain	1/23 (4.3%)	3	1/9 (11.1%)	1	1/10 (10%)	1	0/2 (0%)	0
Pyrexia	0/23 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/2 (0%)	0
Immune system disorders
Mycotic allergy	1/23 (4.3%)	1	0/9 (0%)	0	0/10 (0%)	0	0/2 (0%)	0
Infections and infestations
Cellulitis	1/23 (4.3%)	1	0/9 (0%)	0	0/10 (0%)	0	0/2 (0%)	0
Pharyngitis	1/23 (4.3%)	1	0/9 (0%)	0	0/10 (0%)	0	0/2 (0%)	0
Injury, poisoning and procedural complications
Laceration	0/23 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/2 (0%)	0
Splinter	1/23 (4.3%)	1	0/9 (0%)	0	0/10 (0%)	0	0/2 (0%)	0
Investigations
Blood urine present	0/23 (0%)	0	0/9 (0%)	0	0/10 (0%)	0	1/2 (50%)	1
Metabolism and nutrition disorders
Decreased appetite	0/23 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/2 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	2/23 (8.7%)	4	0/9 (0%)	0	1/10 (10%)	3	0/2 (0%)	0
Back pain	0/23 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	1/2 (50%)	2
Muscle spasms	0/23 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/2 (0%)	0
Musculoskeletal discomfort	0/23 (0%)	0	0/9 (0%)	0	1/10 (10%)	2	0/2 (0%)	0
Musculoskeletal pain	0/23 (0%)	0	0/9 (0%)	0	2/10 (20%)	2	1/2 (50%)	1
Musculoskeletal stiffness	1/23 (4.3%)	1	0/9 (0%)	0	0/10 (0%)	0	0/2 (0%)	0
Pain in extremity	0/23 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	1/2 (50%)	3
Nervous system disorders
Dizziness	1/23 (4.3%)	1	0/9 (0%)	0	0/10 (0%)	0	0/2 (0%)	0
Headache	2/23 (8.7%)	2	2/9 (22.2%)	2	2/10 (20%)	2	1/2 (50%)	1
Sinus headache	0/23 (0%)	0	0/9 (0%)	0	1/10 (10%)	2	0/2 (0%)	0
Somnolence	0/23 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/2 (0%)	0
Psychiatric disorders
Mental status changes	1/23 (4.3%)	1	0/9 (0%)	0	0/10 (0%)	0	0/2 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	1/23 (4.3%)	1	0/9 (0%)	0	1/10 (10%)	1	0/2 (0%)	0
Nasal congestion	2/23 (8.7%)	2	1/9 (11.1%)	1	0/10 (0%)	0	0/2 (0%)	0
Oropharyngeal pain	1/23 (4.3%)	2	0/9 (0%)	0	0/10 (0%)	0	0/2 (0%)	0
Rhinorrhoea	0/23 (0%)	0	0/9 (0%)	0	2/10 (20%)	2	0/2 (0%)	0
Sneezing	0/23 (0%)	0	0/9 (0%)	0	1/10 (10%)	2	0/2 (0%)	0
Skin and subcutaneous tissue disorders
Pityriasis rosea	1/23 (4.3%)	1	0/9 (0%)	0	0/10 (0%)	0	0/2 (0%)	0
Rash	0/23 (0%)	0	0/9 (0%)	0	1/10 (10%)	1	0/2 (0%)	0
Skin lesion	0/23 (0%)	0	1/9 (11.1%)	1	0/10 (0%)	0	0/2 (0%)	0

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The SPONSOR has the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the SPONSOR as confidential must be deleted prior to submission. SPONSOR review can be expedited to meet publication guidelines.