Breast Cancer, Metastatic Bone Disease
Conditions
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.
Interventions
DRUGZA
Single ZA 4 mg IV infusion at the start of treatment
DRUGOdanacatib
Once-daily odanacatib 5 mg tablet for 4 weeks
DRUGOdanacatib matching placebo
Once-daily odanacatib matching placebo for 4 weeks
DRUGZA matching placebo
Single IV infusion of ZA matching placebo given at the start of treatment
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Single IV Infusion of 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. | 14 |
| 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. | 29 |
| Total | 43 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Participant discontinued by mistake | 0 | 1 |
Baseline characteristics
| Characteristic | Single IV Infusion of ZA 4 mg | Once-daily Odanacatib 5 mg | Total |
|---|---|---|---|
| Age, Continuous | 60.3 Years STANDARD_DEVIATION 8.3 | 59.4 Years STANDARD_DEVIATION 10.2 | 59.7 Years STANDARD_DEVIATION 9.5 |
| Sex: Female, Male Female | 14 Participants | 29 Participants | 43 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 14 | 17 / 29 |
| serious Total, serious adverse events | 2 / 14 | 4 / 29 |
Outcome results
Primary
Number of Participants Who Discontinued Treatment Due to an AE
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
Population: All randomized participants who took at least one dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single IV Infusion of ZA 4 mg | Number of Participants Who Discontinued Treatment Due to an AE | 0 Participants |
| Once-daily Odanacatib 5 mg | Number of Participants Who Discontinued Treatment Due to an AE | 2 Participants |
Primary
Number of Participants Who Experienced an Adverse Event (AE)
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
Population: All randomized participants who took at least one dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Single IV Infusion of ZA 4 mg | Number of Participants Who Experienced an Adverse Event (AE) | 10 Participants |
| Once-daily Odanacatib 5 mg | Number of Participants Who Experienced an Adverse Event (AE) | 20 Participants |
Primary
Percentage Change From Baseline in Urinary N-telopeptide of Type I Collagen (u-NTx) at 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.
Time frame: 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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Single IV Infusion of ZA 4 mg | Percentage Change From Baseline in Urinary N-telopeptide of Type I Collagen (u-NTx) at Week 4 | -73 Percentage change |
| Once-daily Odanacatib 5 mg | Percentage Change From Baseline in Urinary N-telopeptide of Type I Collagen (u-NTx) at Week 4 | -77 Percentage change |
Secondary
Percentage Change From Baseline in Urinary Deoxypyridinoline (u-DPD) at 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.
Time frame: 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
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Single IV Infusion of ZA 4 mg | Percentage Change From Baseline in Urinary Deoxypyridinoline (u-DPD) at Week 4 | -52 Percentage change |
| Once-daily Odanacatib 5 mg | Percentage Change From Baseline in Urinary Deoxypyridinoline (u-DPD) at Week 4 | -30 Percentage change |