A Study to Examine the Effects of an Experimental Drug on Women With Breast Cancer and Metastatic Bone Disease (MBD)(0822-016)(COMPLETED)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00399802
• Collaborator: (none)
• Enrollment: 43
• Arms: 2
• Actual Duration (Months): 12.6

Study Details

Study Description

Brief Summary

This is a 4-week study to examine the effects of a new experimental medication on women with breast cancer and established bone metastases. This study will enroll approximately 45 women. The primary hypotheses are: (1) odanacatib will result in a substantial suppression of urinary N-telopeptide of type I collagen (u-NTx) similar to that achieved with an intravenous (IV) infusion of zoledronic acid (ZA) over 4 weeks of treatment; and (2) odanacatib (MK-0822) will be safe and well tolerated during 4 weeks of treatment.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer; Metastatic Bone Disease	Drug: ZA; Drug: Odanacatib; Drug: Odanacatib matching placebo; Drug: ZA matching placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase II Study to Assess the Safety, Tolerability, and Efficacy of MK-0822 (Cathepsin-K Inhibitor) in the Treatment of Women With Breast Cancer and Established Bone Metastases (MBD)
• Actual Study Start Date: Nov 16, 2006
• Actual Primary Completion Date: Dec 5, 2007
• Actual Study Completion Date: Dec 5, 2007

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Single IV infusion of ZA 4 mg Participants will receive a single IV infusion of ZA 4 mg at the start of treatment and a once-daily odanacatib matching placebo tablet for 4 weeks.	Drug: ZA; Single ZA 4 mg IV infusion at the start of treatment; Other Names: Zometa® ; Drug: Odanacatib matching placebo; Once-daily odanacatib matching placebo for 4 weeks
Experimental: Odanacatib 5 mg Participants will receive a once-daily odanacatib 5 mg tablet for 4 weeks and a single IV infusion of ZA matching placebo at the start of treatment.	Drug: Odanacatib; Once-daily odanacatib 5 mg tablet for 4 weeks; Other Names: MK-0822 ; Drug: ZA matching placebo; Single IV infusion of ZA matching placebo given at the start of treatment

Outcome Measures

Primary Outcome Measures

1. Percentage Change From Baseline in Urinary N-telopeptide of Type I Collagen (u-NTx) at Week 4 [Baseline and Week 4]

   u-NTx is a biochemical index of bone resorption. Participants provided urine specimens on Day 1 (baseline) and at Week 4 for measurement of u-NTx.

2. Number of Participants Who Experienced an Adverse Event (AE) [Up to 6 weeks]

   An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.

3. Number of Participants Who Discontinued Treatment Due to an AE [Up to 4 weeks]

   An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.

Secondary Outcome Measures

1. Percentage Change From Baseline in Urinary Deoxypyridinoline (u-DPD) at Week 4 [Baseline and Week 4]

   u-DPD is a biochemical marker of bone resorption. Participants provided urine specimens on Day 1 (baseline) and Week 4 for measurement of u-DPD.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient has histologically or cytologically-confirmed breast cancer

• Patient has documented skeletal metastases

Exclusion Criteria:

• Patient is undergoing current oral bisphosphonate therapy, or has a history of oral bisphosphonate use within 6 months of entry into study

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: NCT00399802
• Other Study ID Numbers: 0822-016; 2006_533; MK-0822-016
• First Posted: Nov 15, 2006
• Last Update Posted: Aug 16, 2018
• Last Verified: Jul 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Breast Neoplasms; Bone Diseases

Study Results

Participant Flow

Arm/Group Title	Single Intravenous (IV) Infusion of Zoledronic Acid (ZA) 4 mg	Once-daily Odanacatib 5 mg
Arm/Group Description	Participants received a single IV infusion of ZA 4 mg at the start of treatment and a once-daily odanacatib matching placebo tablet for 4 weeks.	Participants received a once-daily odanacatib 5 mg tablet for 4 weeks and a single IV infusion of ZA matching placebo at the start of treatment.
Period Title: Overall Study
STARTED	14	29
COMPLETED	14	26
NOT COMPLETED	0	3

Baseline Characteristics

Arm/Group Title	Single IV Infusion of ZA 4 mg	Once-daily Odanacatib 5 mg	Total
Arm/Group Description	Participants received a single IV infusion of ZA 4 mg at the start of treatment and a once-daily odanacatib matching placebo tablet for 4 weeks.	Participants received a once-daily odanacatib 5 mg tablet for 4 weeks and a single IV infusion of ZA matching placebo at the start of treatment.	Total of all reporting groups
Overall Participants	14	29	43
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	60.3 (8.3)	59.4 (10.2)	59.7 (9.5)
Sex: Female, Male (Count of Participants)
Female	14 100%	29 100%	43 100%
Male	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Percentage Change From Baseline in Urinary N-telopeptide of Type I Collagen (u-NTx) at Week 4
Description	u-NTx is a biochemical index of bone resorption. Participants provided urine specimens on Day 1 (baseline) and at Week 4 for measurement of u-NTx.
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description

All randomized participants who took at least one dose of study drug and had available u-NTx data for Baseline and Week 4

Arm/Group Title	Single IV Infusion of ZA 4 mg	Once-daily Odanacatib 5 mg
Arm/Group Description	Participants received a single IV infusion of ZA 4 mg at the start of treatment and a once-daily odanacatib matching placebo tablet for 4 weeks.	Participants received a once-daily odanacatib 5 mg tablet for 4 weeks and a single IV infusion of ZA matching placebo at the start of treatment.
Measure Participants	14	27
Mean (95% Confidence Interval) [Percentage change]	-73	-77

2. Primary Outcome

Title	Number of Participants Who Experienced an Adverse Event (AE)
Description	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Time Frame	Up to 6 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who took at least one dose of study drug

Arm/Group Title	Single IV Infusion of ZA 4 mg	Once-daily Odanacatib 5 mg
Arm/Group Description	Participants received a single IV infusion of ZA 4 mg at the start of treatment and a once-daily odanacatib matching placebo tablet for 4 weeks.	Participants received a once-daily odanacatib 5 mg tablet for 4 weeks and a single IV infusion of ZA matching placebo at the start of treatment.
Measure Participants	14	29
Count of Participants [Participants]	10 71.4%	20 69%

3. Primary Outcome

Title	Number of Participants Who Discontinued Treatment Due to an AE
Description	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a study drug, whether or not it is considered related to the study drug.
Time Frame	Up to 4 weeks

Outcome Measure Data

Analysis Population Description

All randomized participants who took at least one dose of study drug

Arm/Group Title	Single IV Infusion of ZA 4 mg	Once-daily Odanacatib 5 mg
Arm/Group Description	Participants received a single IV infusion of ZA 4 mg at the start of treatment and a once-daily odanacatib matching placebo tablet for 4 weeks.	Participants received a once-daily odanacatib 5 mg tablet for 4 weeks and a single IV infusion of ZA matching placebo at the start of treatment.
Measure Participants	14	29
Count of Participants [Participants]	0 0%	2 6.9%

4. Secondary Outcome

Title	Percentage Change From Baseline in Urinary Deoxypyridinoline (u-DPD) at Week 4
Description	u-DPD is a biochemical marker of bone resorption. Participants provided urine specimens on Day 1 (baseline) and Week 4 for measurement of u-DPD.
Time Frame	Baseline and Week 4

Outcome Measure Data

Analysis Population Description

All randomized participants who took at least one dose of study drug and had available u-DPD data for Baseline and Week 4

Arm/Group Title	Single IV Infusion of ZA 4 mg	Once-daily Odanacatib 5 mg
Arm/Group Description	Participants received a single IV infusion of ZA 4 mg at the start of treatment and a once-daily odanacatib matching placebo tablet for 4 weeks.	Participants received a once-daily odanacatib 5 mg tablet for 4 weeks and a single IV infusion of ZA matching placebo at the start of treatment.
Measure Participants	13	27
Mean (95% Confidence Interval) [Percentage change]	-52	-30

Adverse Events

Time Frame	Up to 6 weeks
Adverse Event Reporting Description	All randomized participants who took at least one dose of study drug
Arm/Group Title	Single IV Infusion of ZA 4 mg		Once-daily Odanacatib 5 mg
Arm/Group Description	Participants received a single IV infusion of ZA 4 mg at the start of treatment and a once-daily odanacatib matching placebo tablet for 4 weeks.		Participants received a once-daily odanacatib 5 mg tablet for 4 weeks and a single IV infusion of ZA matching placebo at the start of treatment.
All Cause Mortality
	Single IV Infusion of ZA 4 mg		Once-daily Odanacatib 5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Single IV Infusion of ZA 4 mg		Once-daily Odanacatib 5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/14 (14.3%)		4/29 (13.8%)
Blood and lymphatic system disorders
Febrile neutropenia	0/14 (0%)	0	1/29 (3.4%)	1
Gastrointestinal disorders
Ascites	0/14 (0%)	0	1/29 (3.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer metastatic	1/14 (7.1%)	1	0/29 (0%)	0
Metastases to bone	1/14 (7.1%)	1	2/29 (6.9%)	2
Other (Not Including Serious) Adverse Events
	Single IV Infusion of ZA 4 mg		Once-daily Odanacatib 5 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/14 (71.4%)		17/29 (58.6%)
Cardiac disorders
Palpitations	1/14 (7.1%)	1	1/29 (3.4%)	1
Gastrointestinal disorders
Diarrhoea	2/14 (14.3%)	2	1/29 (3.4%)	1
Nausea	3/14 (21.4%)	5	2/29 (6.9%)	2
Vomiting	1/14 (7.1%)	1	5/29 (17.2%)	5
General disorders
Asthenia	0/14 (0%)	0	2/29 (6.9%)	3
Chills	1/14 (7.1%)	1	0/29 (0%)	0
Fatigue	2/14 (14.3%)	2	1/29 (3.4%)	1
Oedema	1/14 (7.1%)	1	0/29 (0%)	0
Pain	1/14 (7.1%)	1	0/29 (0%)	0
Pyrexia	1/14 (7.1%)	1	0/29 (0%)	0
Infections and infestations
Herpes virus infection	1/14 (7.1%)	1	0/29 (0%)	0
Influenza	1/14 (7.1%)	1	1/29 (3.4%)	1
Investigations
Blood calcium decreased	1/14 (7.1%)	1	0/29 (0%)	0
Blood sodium decreased	1/14 (7.1%)	1	0/29 (0%)	0
Haematocrit decreased	1/14 (7.1%)	1	0/29 (0%)	0
Haemoglobin decreased	1/14 (7.1%)	1	0/29 (0%)	0
Lymphocyte count decreased	4/14 (28.6%)	8	6/29 (20.7%)	11
Metamyelocyte count increased	1/14 (7.1%)	1	0/29 (0%)	0
Monocyte count increased	1/14 (7.1%)	1	0/29 (0%)	0
Platelet count decreased	1/14 (7.1%)	1	0/29 (0%)	0
Red blood cell count decreased	1/14 (7.1%)	1	0/29 (0%)	0
Weight decreased	1/14 (7.1%)	1	0/29 (0%)	0
White blood cell count decreased	1/14 (7.1%)	1	1/29 (3.4%)	1
Metabolism and nutrition disorders
Anorexia	1/14 (7.1%)	1	0/29 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/14 (0%)	0	3/29 (10.3%)	4
Bone pain	3/14 (21.4%)	4	2/29 (6.9%)	3
Muscle spasms	1/14 (7.1%)	1	2/29 (6.9%)	2
Musculoskeletal chest pain	0/14 (0%)	0	2/29 (6.9%)	2
Myalgia	1/14 (7.1%)	1	0/29 (0%)	0
Nervous system disorders
Dizziness	1/14 (7.1%)	1	0/29 (0%)	0
Headache	2/14 (14.3%)	2	4/29 (13.8%)	5
Paraesthesia	1/14 (7.1%)	1	0/29 (0%)	0
Vascular disorders
Phlebitis	1/14 (7.1%)	1	0/29 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The SPONSOR must have 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.