Trial Outcomes & Findings for A Study to Examine the Effects of an Experimental Drug on Women With Breast Cancer and Metastatic Bone Disease (MBD)(0822-016)(COMPLETED) (NCT NCT00399802)

Last Updated: 2018-08-16

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

43 participants

Primary outcome timeframe

Baseline and Week 4

Results posted on

2018-08-16

Participant Flow

Participant milestones

Participant milestones
Measure	Single Intravenous (IV) Infusion of Zoledronic Acid (ZA) 4 mg 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.	Once-daily Odanacatib 5 mg 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.
Overall Study STARTED	14	29
Overall Study COMPLETED	14	26
Overall Study NOT COMPLETED	0	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Single Intravenous (IV) Infusion of Zoledronic Acid (ZA) 4 mg 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.	Once-daily Odanacatib 5 mg 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.
Overall Study Adverse Event	0	2
Overall Study Participant discontinued by mistake	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Single IV Infusion of ZA 4 mg n=14 Participants 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.	Once-daily Odanacatib 5 mg n=29 Participants 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 n=43 Participants Total of all reporting groups
Age, Continuous	60.3 Years STANDARD_DEVIATION 8.3 • n=113 Participants	59.4 Years STANDARD_DEVIATION 10.2 • n=163 Participants	59.7 Years STANDARD_DEVIATION 9.5 • n=160 Participants
Sex: Female, Male Female	14 Participants n=113 Participants	29 Participants n=163 Participants	43 Participants n=160 Participants
Sex: Female, Male Male	0 Participants n=113 Participants	0 Participants n=163 Participants	0 Participants n=160 Participants

PRIMARY outcome

Timeframe: Baseline and Week 4

Population: All randomized participants who took at least one dose of study drug and had available u-NTx data for 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.

Outcome measures

Outcome measures
Measure	Single IV Infusion of ZA 4 mg n=14 Participants 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.	Once-daily Odanacatib 5 mg n=27 Participants 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.
Percentage Change From Baseline in Urinary N-telopeptide of Type I Collagen (u-NTx) at Week 4	-73 Percentage change Interval -80.0 to -62.0	-77 Percentage change Interval -82.0 to -71.0

PRIMARY outcome

Timeframe: Up to 6 weeks

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

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.

Outcome measures

Outcome measures
Measure	Single IV Infusion of ZA 4 mg n=14 Participants 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.	Once-daily Odanacatib 5 mg n=29 Participants 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.
Number of Participants Who Experienced an Adverse Event (AE)	10 Participants	20 Participants

PRIMARY outcome

Timeframe: Up to 4 weeks

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

Outcome measures

Outcome measures
Measure	Single IV Infusion of ZA 4 mg n=14 Participants 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.	Once-daily Odanacatib 5 mg n=29 Participants 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.
Number of Participants Who Discontinued Treatment Due to an AE	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline and Week 4

Population: All randomized participants who took at least one dose of study drug and had available u-DPD data for 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.

Outcome measures

Outcome measures
Measure	Single IV Infusion of ZA 4 mg n=13 Participants 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.	Once-daily Odanacatib 5 mg n=27 Participants 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.
Percentage Change From Baseline in Urinary Deoxypyridinoline (u-DPD) at Week 4	-52 Percentage change Interval -64.0 to -36.0	-30 Percentage change Interval -43.0 to -15.0

Adverse Events

Single IV Infusion of ZA 4 mg

Serious events: 2 serious events

Other events: 10 other events

Deaths: 0 deaths

Once-daily Odanacatib 5 mg

Serious events: 4 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Single IV Infusion of ZA 4 mg n=14 participants at risk 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.	Once-daily Odanacatib 5 mg n=29 participants at risk 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.
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/14 • Up to 6 weeks All randomized participants who took at least one dose of study drug	3.4% 1/29 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Gastrointestinal disorders Ascites	0.00% 0/14 • Up to 6 weeks All randomized participants who took at least one dose of study drug	3.4% 1/29 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer metastatic	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to bone	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	6.9% 2/29 • Number of events 2 • Up to 6 weeks All randomized participants who took at least one dose of study drug

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	Single IV Infusion of ZA 4 mg n=14 participants at risk 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.	Once-daily Odanacatib 5 mg n=29 participants at risk 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.
Cardiac disorders Palpitations	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	3.4% 1/29 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Gastrointestinal disorders Diarrhoea	14.3% 2/14 • Number of events 2 • Up to 6 weeks All randomized participants who took at least one dose of study drug	3.4% 1/29 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Gastrointestinal disorders Nausea	21.4% 3/14 • Number of events 5 • Up to 6 weeks All randomized participants who took at least one dose of study drug	6.9% 2/29 • Number of events 2 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Gastrointestinal disorders Vomiting	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	17.2% 5/29 • Number of events 5 • Up to 6 weeks All randomized participants who took at least one dose of study drug
General disorders Asthenia	0.00% 0/14 • Up to 6 weeks All randomized participants who took at least one dose of study drug	6.9% 2/29 • Number of events 3 • Up to 6 weeks All randomized participants who took at least one dose of study drug
General disorders Chills	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug
General disorders Fatigue	14.3% 2/14 • Number of events 2 • Up to 6 weeks All randomized participants who took at least one dose of study drug	3.4% 1/29 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug
General disorders Oedema	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug
General disorders Pain	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug
General disorders Pyrexia	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Infections and infestations Herpes virus infection	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Infections and infestations Influenza	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	3.4% 1/29 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Investigations Blood calcium decreased	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Investigations Blood sodium decreased	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Investigations Haematocrit decreased	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Investigations Haemoglobin decreased	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Investigations Lymphocyte count decreased	28.6% 4/14 • Number of events 8 • Up to 6 weeks All randomized participants who took at least one dose of study drug	20.7% 6/29 • Number of events 11 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Investigations Metamyelocyte count increased	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Investigations Monocyte count increased	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Investigations Platelet count decreased	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Investigations Red blood cell count decreased	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Investigations Weight decreased	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Investigations White blood cell count decreased	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	3.4% 1/29 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Metabolism and nutrition disorders Anorexia	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/14 • Up to 6 weeks All randomized participants who took at least one dose of study drug	10.3% 3/29 • Number of events 4 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Musculoskeletal and connective tissue disorders Bone pain	21.4% 3/14 • Number of events 4 • Up to 6 weeks All randomized participants who took at least one dose of study drug	6.9% 2/29 • Number of events 3 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Musculoskeletal and connective tissue disorders Muscle spasms	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	6.9% 2/29 • Number of events 2 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/14 • Up to 6 weeks All randomized participants who took at least one dose of study drug	6.9% 2/29 • Number of events 2 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Musculoskeletal and connective tissue disorders Myalgia	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Nervous system disorders Dizziness	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Nervous system disorders Headache	14.3% 2/14 • Number of events 2 • Up to 6 weeks All randomized participants who took at least one dose of study drug	13.8% 4/29 • Number of events 5 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Nervous system disorders Paraesthesia	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug
Vascular disorders Phlebitis	7.1% 1/14 • Number of events 1 • Up to 6 weeks All randomized participants who took at least one dose of study drug	0.00% 0/29 • Up to 6 weeks All randomized participants who took at least one dose of study drug