Denosumab (AMG 162) in Bisphosphonate Naive Metastatic Br... | NCT00091832

Denosumab (AMG 162) in Bisphosphonate Naive Metastatic Br... | NCT00091832 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Denosumab 60 mg every 12 weeks	Experimental	Denosumab 60 mg by subcutaneous injection once every 12 weeks (Q12W) for 25 weeks.	Biological: Denosumab
Denosumab 120 mg every 4 weeks	Experimental	Denosumab 120 mg by subcutaneous injection once every 4 weeks (Q4W) for 25 weeks.	Biological: Denosumab
Denosumab 180 mg every 4 weeks	Experimental	Denosumab 180 mg by subcutaneous injection once every 4 weeks (Q4W) for 25 weeks.	Biological: Denosumab
IV bisphosphonates every 4 weeks	Active Comparator	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion for 25 weeks.	Drug: IV Bisphosphonates
Denosumab 180 mg every 12 weeks	Experimental	Denosumab 180 mg by subcutaneous injection once every 12 weeks (Q12W) for 25 weeks.	Biological: Denosumab
Denosumab 30 mg every 4 weeks

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Denosumab	Biological	Denosumab administered by subcutaneous injection	Denosumab 120 mg every 4 weeks Denosumab 180 mg every 12 weeks Denosumab 180 mg every 4 weeks

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percent Change From Baseline to Week 13 in Creatinine-adjusted Urinary N-telopeptide (uNTx/Cr)	Percent change from Baseline to Week 13 in Urinary N-telopeptide corrected by creatinine (uNTx/Cr) calculated using ((Week 13 value - Baseline value) / Baseline value ) x 100.	Baseline and Week 13

Secondary Outcomes

Measure	Description	Time Frame
Percent Change From Baseline to Week 25 in Urinary N-telopeptide (uNTx)	Percent change from Baseline to Week 25 in Urinary N-telopeptide (uNTx) calculated using ((Week 25 value - Baseline value) / Baseline value) x 100.	Baseline and Week 25
Number of Participants Achieving 65% or More Reduction in Urinary N-telopeptide (uNTx) From Baseline at Week 13

Name	Affiliation	Role
MD	Amgen	Study Director

References Module

Citations

PubMed Identifier	Type	Citation
	Background	Campbell-Baird C, Lipton A, Sarkenshik M, Ma H, Jun S.Incidence of Acute Phase Events Following Denosumab or Intravenous Bisphosphonates: Results From a Randomized, Controlled Phase 2 Study in Patients With Breast Cancer and Bone Metastases.Journal-001752;2010;7:85-89.
18927312	Background	Lipton A, Steger GG, Figueroa J, Alvarado C, Solal-Celigny P, Body JJ, de Boer R, Berardi R, Gascon P, Tonkin KS, Coleman RE, Paterson AH, Gao GM, Kinsey AC, Peterson MC, Jun S. Extended efficacy and safety of denosumab in breast cancer patients with bone metastases not receiving prior bisphosphonate therapy. Clin Cancer Res. 2008 Oct 15;14(20):6690-6. doi: 10.1158/1078-0432.CCR-07-5234.
17785705

Label	URL
AmgenTrials clinical trials website	View source

Arm/Group Information

ID	Title	Description
FG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion (IV)
FG001	Denosumab 30 mg Q4W	Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)
FG002	Denosumab 120 mg Q4W	Denosumab 120 mg by subcutaneous injection every 4 weeks (Q4W)
FG003	Denosumab 180 mg Q4W	Denosumab 180 mg by subcutaneous injection every 4 weeks (Q4W)
FG004	Denosumab 60 mg Q12W	Denosumab 60 mg by subcutaneous injection every 12 weeks (Q12W)
FG005	Denosumab 180 mg Q12W	Denosumab 180 mg by subcutaneous injection every 12 weeks (Q12W)

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG00043 subjects FG00142 subjects FG00242 subjects FG00343 subjects FG00442 subjects FG00543 subjects
Received Study Medication		FG00043 subjects FG00142 subjects FG00241 subjects FG00343 subjects FG004
COMPLETED		FG00029 subjects FG00131 subjects FG00230 subjects FG00329 subjects FG004
NOT COMPLETED		FG00014 subjects FG00111 subjects FG00212 subjects FG00314 subjects FG004

Type	Comment	Reasons
Physician Decision		FG0001 subjects FG0010 subjects FG0020 subjects FG003

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
BG001	Denosumab 30 mg Q4W	Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percent Change From Baseline to Week 13 in Creatinine-adjusted Urinary N-telopeptide (uNTx/Cr)

Percent change from Baseline to Week 13 in Urinary N-telopeptide corrected by creatinine (uNTx/Cr) calculated using ((Week 13 value - Baseline value) / Baseline value ) x 100.

Primary Efficacy Subset, composed of all participants who were randomized, received at least one dose of denosumab or bisphosphonate, and had both a baseline and at least one postbaseline measurement of Urinary N-telopeptide corrected by creatinine (uNTx/Cr). Analysis was by Intention-to-Treat (ITT).

Posted

Mean

Standard Deviation

Percent change

Baseline and Week 13

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
OG001

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 9.0	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 9.0	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Study Director	Amgen Inc.	866-572-6436

Condition Browse Module

ID	Term
D001943	Breast Neoplasms
D009362	Neoplasm Metastasis
D009369	Neoplasms

ID	Term
D009371	Neoplasms by Site
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

Intervention Browse Module

ID	Term
D000069448	Denosumab
D004164	Diphosphonates

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins

Race/Ethnicity, Customized

Number

Participants

Title

Denominators

Categories

White or Caucasian

Title	Measurements
	BG00025 BG00128 BG00229 BG00334 BG00430 BG00533 BG006179

Hispanic or Latino

Title	Measurements
	BG00016 BG00113 BG00213 BG003

Asian

Title	Measurements
	BG0001 BG0010 BG0020 BG003

Native Hawaiian or Other Pacific Islander

Title	Measurements
	BG0000 BG0011 BG0020 BG003

Other

Title	Measurements
	BG0001 BG0010 BG0020 BG003

uNTx/Cr

Urinary N-telopeptide corrected by creatinine (uNTx/Cr)

Mean

Standard Deviation

nmol/mmol

Title

Denominators

Categories

Title	Measurements
	BG00083.16± 94.37 BG00166.44± 61.17 BG00289.41± 98.58 BG00375.92± 91.03 BG004102.06± 129.12 BG00598.22± 168.42 BG00685.78± 111.94

Serum CTx

Type I serum C-Telopeptide (CTx)

Mean

Standard Deviation

ng/mL

Title

Denominators

Categories

Title	Measurements
	BG0000.592± 0.284 BG0010.632± 0.430 BG0020.720± 0.559 BG0030.647± 0.703 BG0040.714± 0.564 BG0050.846± 0.892 BG0060.692± 0.605

TRAP 5b

Tartrate-resistant acid phosphatase 5b (TRAP 5b)

Mean

Standard Deviation

U/L

Title

Denominators

Categories

Title	Measurements
	BG0006.907± 3.280 BG0016.879± 2.878 BG0027.116± 3.493 BG0037.628± 6.830 BG0046.765± 4.340 BG0057.009± 4.217 BG0067.057± 4.358

BSAP

Bone specific alkaline phosphatase (BSAP)

Mean

Standard Deviation

U/L

Title

Denominators

Categories

Title	Measurements
	BG00054.84± 51.69 BG00144.33± 26.06 BG00245.62± 26.02 BG00362.39± 109.18 BG00447.89± 30.46 BG00548.82± 35.13 BG00650.75± 55.04

P1NP

Procollagen 1 N-terminal peptide (P1NP)

Mean

Standard Deviation

µg/L

Title

Denominators

Categories

Title	Measurements
	BG000111.01± 97.21 BG00198.54± 72.69 BG002114.29± 113.51 BG003193.03± 641.13 BG00498.47± 83.46 BG005139.01± 188.02 BG006126.20± 284.81

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002 OG003 OG004 OG005		ANCOVA	Adjusted for the stratum to which the participant was originally assigned by the Interactive Voice Response System (IVRS)	0.245													No	Superiority or Other

Secondary

Percent Change From Baseline to Week 25 in Urinary N-telopeptide (uNTx)

Percent change from Baseline to Week 25 in Urinary N-telopeptide (uNTx) calculated using ((Week 25 value - Baseline value) / Baseline value) x 100.

Posted

Mean

Standard Deviation

Percent change

Baseline and Week 25

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
OG001	Denosumab 30 mg Q4W	Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)
OG002	Denosumab 120 mg Q4W	Denosumab 120 mg by subcutaneous injection every 4 weeks (Q4W)
OG003	Denosumab 180 mg Q4W	Denosumab 180 mg by subcutaneous injection every 4 weeks (Q4W)
OG004	Denosumab 60 mg Q12W	Denosumab 60 mg by subcutaneous injection every 12 weeks (Q12W)
OG005	Denosumab 180 mg Q12W	Denosumab 180 mg by subcutaneous injection every 12 weeks (Q12W)

Units	Counts
Participants	OG00034 OG00136 OG00234 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-39.52± 74.16 OG001-53.46± 100.77 OG002-43.16± 101.08 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002 OG003 OG004 OG005		ANCOVA	Adjusted for the stratum to which the participant was originally assigned by the Interactive Voice Response System (IVRS)	0.848													No	Superiority or Other

Secondary

Number of Participants Achieving 65% or More Reduction in Urinary N-telopeptide (uNTx) From Baseline at Week 13

The number of participants achieving a 65% reduction or more in uNTx from Baseline at Week 13. Calculation used is ((Week 13 value - Baseline value) / Baseline value ) x 100 and participants were considered having a 65% reduction or more if their value was ≤ -65%.

Primary Efficacy Subset, composed of all participants who were randomized, received at least one dose of denosumab or bisphosphonate, and had both a Baseline and at least one postbaseline measurement of Urinary N-telopeptide corrected by creatinine (uNTx/Cr). Analysis was by Intention-to-Treat (ITT).

Posted

Number

Participants

Baseline and Week 13

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
OG001	Denosumab 30 mg Q4W	Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)
OG002	Denosumab 120 mg Q4W	Denosumab 120 mg by subcutaneous injection every 4 weeks (Q4W)
OG003	Denosumab 180 mg Q4W	Denosumab 180 mg by subcutaneous injection every 4 weeks (Q4W)
OG004	Denosumab 60 mg Q12W	Denosumab 60 mg by subcutaneous injection every 12 weeks (Q12W)
OG005	Denosumab 180 mg Q12W	Denosumab 180 mg by subcutaneous injection every 12 weeks (Q12W)

Units	Counts
Participants	OG00041 OG00141 OG00240 OG003

Title

Denominators

Categories

Title	Measurements
	OG00025 OG00124 OG00226 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG004						Odds Ratio (OR)	1.72				95	0.68	4.35			Adjusted for the stratum to which the participant was originally assigned by the Interactive Voice Response System (IVRS)	No	Superiority or Other
OG000 OG003

Secondary

Number of Participants Achieving 65% or More Reduction in uNTX From Baseline at Week 25

The number of participants achieving a 65% reduction or more in uNTX from Baseline at Week 25. Calculation used is ((Week 25 value - Baseline value) / Baseline value) x 100 and participants were considered having a 65% reduction or more if their value was ≤ -65%.

Posted

Number

Participants

Baseline and Week 25

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
OG001	Denosumab 30 mg Q4W	Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)
OG002	Denosumab 120 mg Q4W	Denosumab 120 mg by subcutaneous injection every 4 weeks (Q4W)
OG003	Denosumab 180 mg Q4W	Denosumab 180 mg by subcutaneous injection every 4 weeks (Q4W)
OG004	Denosumab 60 mg Q12W	Denosumab 60 mg by subcutaneous injection every 12 weeks (Q12W)
OG005	Denosumab 180 mg Q12W	Denosumab 180 mg by subcutaneous injection every 12 weeks (Q12W)

Units	Counts
Participants	OG00041 OG00141 OG00240 OG003

Title

Denominators

Categories

Title	Measurements
	OG00019 OG00125 OG00223 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG005						Odds Ratio (OR)	1.82				95	0.69	4.79			Adjusted for the stratum to which the participant was originally assigned by the Interactive Voice Response System (IVRS)	No	Superiority or Other
OG000 OG003

Secondary

Time to 65% or More Reduction in Urinary N-telopeptide (uNTX) From Baseline

Kaplan-Meier estimate of the median time from enrollment to the first occurrence of a reduction of uNTx of ≥ 65% compared to Baseline. For participants whose uNTx did not fall below 65% of the Baseline value, the time was censored at time of last evaluation of uNTx.

Posted

Median

Inter-Quartile Range

Days

Baseline to Week 57

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
OG001	Denosumab 30 mg Q4W	Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)
OG002	Denosumab 120 mg Q4W	Denosumab 120 mg by subcutaneous injection every 4 weeks (Q4W)
OG003	Denosumab 180 mg Q4W	Denosumab 180 mg by subcutaneous injection every 4 weeks (Q4W)
OG004	Denosumab 60 mg Q12W	Denosumab 60 mg by subcutaneous injection every 12 weeks (Q12W)
OG005	Denosumab 180 mg Q12W	Denosumab 180 mg by subcutaneous injection every 12 weeks (Q12W)

Units	Counts
Participants	OG00041 OG00141 OG00240 OG003

Title

Denominators

Categories

Title	Measurements
	OG00010(8 to 86) OG00113(8 to 57) OG00211(9 to 43) OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG005						Hazard Ratio (HR)	0.82				95	0.51	1.31			A hazard ratio >1 indicates that the time to 65% or more reduction in uNTx from baseline was shorter in the Denosumab-treated group than in the control group.	No	Superiority or Other
OG000 OG003

Secondary

Percent Change From Baseline to Week 13 in Serum C-Telopeptide (CTX)

Percent change from Baseline to Week 13 in type I serum C-telopeptide (CTX) calculated using ((Week 13 value - Baseline value) / Baseline value) x 100.

Posted

Mean

Standard Deviation

Percent change

Baseline and week 13

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
OG001	Denosumab 30 mg Q4W	Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)
OG002	Denosumab 120 mg Q4W	Denosumab 120 mg by subcutaneous injection every 4 weeks (Q4W)
OG003	Denosumab 180 mg Q4W	Denosumab 180 mg by subcutaneous injection every 4 weeks (Q4W)
OG004	Denosumab 60 mg Q12W	Denosumab 60 mg by subcutaneous injection every 12 weeks (Q12W)
OG005	Denosumab 180 mg Q12W	Denosumab 180 mg by subcutaneous injection every 12 weeks (Q12W)

Units	Counts
Participants	OG00038 OG00139 OG00238 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-66.92± 44.05 OG001-80.76± 12.66 OG002-78.45± 28.89 OG003

Secondary

Percent Change From Baseline to Week 25 in Serum C-telopeptide (CTX)

Percent change from Baseline to Week 25 in type I serum C-telopeptide calculated using ((Week 25 value - Baseline value) / Baseline value) x 100.

Posted

Mean

Standard Deviation

Percent change

Baseline and Week 25

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
OG001	Denosumab 30 mg Q4W	Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)
OG002	Denosumab 120 mg Q4W	Denosumab 120 mg by subcutaneous injection every 4 weeks (Q4W)
OG003	Denosumab 180 mg Q4W	Denosumab 180 mg by subcutaneous injection every 4 weeks (Q4W)
OG004	Denosumab 60 mg Q12W	Denosumab 60 mg by subcutaneous injection every 12 weeks (Q12W)
OG005	Denosumab 180 mg Q12W	Denosumab 180 mg by subcutaneous injection every 12 weeks (Q12W)

Units	Counts
Participants	OG00034 OG00136 OG00234 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-73.09± 22.42 OG001-82.70± 11.92 OG002-74.48± 30.26 OG003

Secondary

Percent Change From Baseline to Week 13 in Procollagen I N-terminal Peptide (P1NP)

Percent change from Baseline to Week 13 in procollagen 1 N-terminal peptide calculated using ((Week 13 value - Baseline value) / Baseline value) x 100.

Posted

Mean

Standard Deviation

Percent change

Baseline and Week 13

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
OG001	Denosumab 30 mg Q4W	Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)
OG002	Denosumab 120 mg Q4W	Denosumab 120 mg by subcutaneous injection every 4 weeks (Q4W)
OG003	Denosumab 180 mg Q4W	Denosumab 180 mg by subcutaneous injection every 4 weeks (Q4W)
OG004	Denosumab 60 mg Q12W	Denosumab 60 mg by subcutaneous injection every 12 weeks (Q12W)
OG005	Denosumab 180 mg Q12W	Denosumab 180 mg by subcutaneous injection every 12 weeks (Q12W)

Units	Counts
Participants	OG00037 OG00139 OG00237 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-50.75± 29.47 OG001-52.35± 36.90 OG002-48.23± 36.83 OG003

Secondary

Percent Change From Baseline to Week 25 in P1NP

Percent change from Baseline to Week 25 in procollagen 1 N-terminal peptide (P1NP) calculated using ((Week 25 value - Baseline value) / Baseline value ) x 100.

Posted

Mean

Standard Deviation

Percent change

Baseline and Week 25

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
OG001	Denosumab 30 mg Q4W	Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)
OG002	Denosumab 120 mg Q4W	Denosumab 120 mg by subcutaneous injection every 4 weeks (Q4W)
OG003	Denosumab 180 mg Q4W	Denosumab 180 mg by subcutaneous injection every 4 weeks (Q4W)
OG004	Denosumab 60 mg Q12W	Denosumab 60 mg by subcutaneous injection every 12 weeks (Q12W)
OG005	Denosumab 180 mg Q12W	Denosumab 180 mg by subcutaneous injection every 12 weeks (Q12W)

Units	Counts
Participants	OG00034 OG00136 OG00234 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-50.48± 41.22 OG001-53.48± 54.79 OG002-55.90± 30.66 OG003

Secondary

Percent Change From Baseline to Week 13 in Tartrate-resistant Acid Phosphatase 5b (TRAP5b)

Percent change from Baseline to Week 13 in tartrate-resistant acid phosphatase 5b calculated using ((Week 13 value - Baseline value) / Baseline value) x 100.

Posted

Mean

Standard Deviation

Percent change

Baseline and Week 13

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
OG001	Denosumab 30 mg Q4W	Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)
OG002	Denosumab 120 mg Q4W	Denosumab 120 mg by subcutaneous injection every 4 weeks (Q4W)
OG003	Denosumab 180 mg Q4W	Denosumab 180 mg by subcutaneous injection every 4 weeks (Q4W)
OG004	Denosumab 60 mg Q12W	Denosumab 60 mg by subcutaneous injection every 12 weeks (Q12W)
OG005	Denosumab 180 mg Q12W	Denosumab 180 mg by subcutaneous injection every 12 weeks (Q12W)

Units	Counts
Participants	OG00036 OG00138 OG00235 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-37.45± 19.87 OG001-56.07± 17.80 OG002-58.24± 15.07 OG003

Secondary

Percent Change From Baseline to Week 25 in Tartrate-resistant Acid Phosphatase 5b (TRAP5b)

Percent change from Baseline to Week 25 in TRAP5b calculated using ((Week 25 value - Baseline value) / Baseline value) x 100.

Posted

Mean

Standard Deviation

Percent change

Baseline and Week 25

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
OG001	Denosumab 30 mg Q4W	Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)
OG002	Denosumab 120 mg Q4W	Denosumab 120 mg by subcutaneous injection every 4 weeks (Q4W)
OG003	Denosumab 180 mg Q4W	Denosumab 180 mg by subcutaneous injection every 4 weeks (Q4W)
OG004	Denosumab 60 mg Q12W	Denosumab 60 mg by subcutaneous injection every 12 weeks (Q12W)
OG005	Denosumab 180 mg Q12W	Denosumab 180 mg by subcutaneous injection every 12 weeks (Q12W)

Units	Counts
Participants	OG00033 OG00135 OG00232 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-38.59± 26.06 OG001-58.58± 18.93 OG002-52.39± 25.30 OG003

Secondary

Percent Change From Baseline to Week 13 in Bone Specific Alkaline Phosphatase (BSAP)

Percent change from Baseline to Week 13 in bone specific alkaline phosphatase (BSAP) calculated using ((Week 13 value - Baseline value) / Baseline value) x 100.

Posted

Mean

Standard Deviation

Percent change

Baseline and Week 13

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
OG001	Denosumab 30 mg Q4W	Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)
OG002	Denosumab 120 mg Q4W	Denosumab 120 mg by subcutaneous injection every 4 weeks (Q4W)
OG003	Denosumab 180 mg Q4W	Denosumab 180 mg by subcutaneous injection every 4 weeks (Q4W)
OG004	Denosumab 60 mg Q12W	Denosumab 60 mg by subcutaneous injection every 12 weeks (Q12W)
OG005	Denosumab 180 mg Q12W	Denosumab 180 mg by subcutaneous injection every 12 weeks (Q12W)

Units	Counts
Participants	OG00036 OG00138 OG00235 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-40.01± 24.42 OG00126.37± 406.79 OG002-40.23± 27.34 OG003

Secondary

Percent Change From Baseline to Week 25 in Bone Specific Alkaline Phosphatase (BSAP)

Percent change from Baseline to Week 25 in BSAP calculated using ((Week 25 value - Baseline value) / Baseline value) x 100.

Posted

Mean

Standard Deviation

Percent change

Baseline and Week 25

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
OG001	Denosumab 30 mg Q4W	Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)
OG002	Denosumab 120 mg Q4W	Denosumab 120 mg by subcutaneous injection every 4 weeks (Q4W)
OG003	Denosumab 180 mg Q4W	Denosumab 180 mg by subcutaneous injection every 4 weeks (Q4W)
OG004	Denosumab 60 mg Q12W	Denosumab 60 mg by subcutaneous injection every 12 weeks (Q12W)
OG005	Denosumab 180 mg Q12W	Denosumab 180 mg by subcutaneous injection every 12 weeks (Q12W)

Units	Counts
Participants	OG00034 OG00135 OG00232 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-46.56± 26.02 OG00115.88± 347.47 OG002-49.01± 21.24 OG003

Secondary

Percent Change From Baseline to Week 13 in Osteocalcin

Percent change from Baseline to Week 13 in osteocalcin calculated using ((Week 13 value - Baseline value) / Baseline value ) x 100.

Posted

Mean

Standard Deviation

Percent change

Baseline and Week 13

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
OG001	Denosumab 30 mg Q4W	Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)
OG002	Denosumab 120 mg Q4W	Denosumab 120 mg by subcutaneous injection every 4 weeks (Q4W)
OG003	Denosumab 180 mg Q4W	Denosumab 180 mg by subcutaneous injection every 4 weeks (Q4W)
OG004	Denosumab 60 mg Q12W	Denosumab 60 mg by subcutaneous injection every 12 weeks (Q12W)
OG005	Denosumab 180 mg Q12W	Denosumab 180 mg by subcutaneous injection every 12 weeks (Q12W)

Units	Counts
Participants	OG00036 OG00138 OG00235 OG003

Title

Denominators

Categories

Title	Measurements
	OG0006.82± 49.78 OG001-19.35± 38.71 OG002-2.39± 47.96 OG003

Secondary

Percent Change From Baseline to Week 25 in Osteocalcin

Percent change from Baseline to Week 25 in osteocalcin calculated using ((Week 25 value - Baseline value) / Baseline value) x 100.

Posted

Mean

Standard Deviation

Percent change

Baseline and Week 25

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
OG001	Denosumab 30 mg Q4W	Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)
OG002	Denosumab 120 mg Q4W	Denosumab 120 mg by subcutaneous injection every 4 weeks (Q4W)
OG003	Denosumab 180 mg Q4W	Denosumab 180 mg by subcutaneous injection every 4 weeks (Q4W)
OG004	Denosumab 60 mg Q12W	Denosumab 60 mg by subcutaneous injection every 12 weeks (Q12W)
OG005	Denosumab 180 mg Q12W	Denosumab 180 mg by subcutaneous injection every 12 weeks (Q12W)

Units	Counts
Participants	OG00034 OG00135 OG00232 OG003

Title

Denominators

Categories

Title	Measurements
	OG000-4.74± 86.98 OG001-30.78± 34.94 OG002-22.80± 46.36 OG003

Secondary

Time to First Skeletal Related Event

Skeletal Related Event (SRE) defined as ≥ 1 of the following: pathological bone fracture, spinal cord compression, surgery or radiation therapy to bone (including the use of radioisotopes).

All participants who were exposed to investigational product.

Posted

Median

95% Confidence Interval

Days

Day 1 to Week 25

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
OG001	Denosumab 30 mg Q4W	Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)
OG002	Denosumab 120 mg Q4W	Denosumab 120 mg by subcutaneous injection every 4 weeks (Q4W)
OG003	Denosumab 180 mg Q4W	Denosumab 180 mg by subcutaneous injection every 4 weeks (Q4W)
OG004	Denosumab 60 mg Q12W	Denosumab 60 mg by subcutaneous injection every 12 weeks (Q12W)
OG005	Denosumab 180 mg Q12W	Denosumab 180 mg by subcutaneous injection every 12 weeks (Q12W)

Units	Counts
Participants	OG00043 OG00142 OG00241 OG003

Title

Denominators

Categories

Title	Measurements
	OG000NA(NA to NA)Median could not be calculated due to the low number of skeletal-related events OG001NA(NA to NA)Median could not be calculated due to the low number of skeletal-related events OG002

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001						Hazard Ratio (HR)	0.543				95	0.159	1.856			A hazard ratio <1 indicates the time to the first skeletal-related event in the denosumab-treated group was longer than that in the control group.	No	Superiority or Other
OG000 OG004

Secondary

Number of Participants With Skeletal Related Events

Skeletal Related Events (SRE) are defined as ≥ 1 of the following: pathological bone fracture, spinal cord compression, surgery or radiation therapy to bone (including the use of radioisotopes).

All participants who were exposed to investigational product.

Posted

Number

Participants

From Day 1 to Week 25

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
OG001	Denosumab 30 mg Q4W	Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)
OG002	Denosumab 120 mg Q4W	Denosumab 120 mg by subcutaneous injection every 4 weeks (Q4W)
OG003	Denosumab 180 mg Q4W	Denosumab 180 mg by subcutaneous injection every 4 weeks (Q4W)
OG004	Denosumab 60 mg Q12W	Denosumab 60 mg by subcutaneous injection every 12 weeks (Q12W)
OG005	Denosumab 180 mg Q12W	Denosumab 180 mg by subcutaneous injection every 12 weeks (Q12W)

Units	Counts
Participants	OG00043 OG00142 OG00241 OG003

Title

Denominators

Categories

Title	Measurements
	OG0007 OG0014 OG0028 OG003

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG005						Odds Ratio (OR)	1.92				95	0.51	7.17			Adjusted for the stratum to which the participant was originally assigned by the Interactive Voice Response System (IVRS)	No	Superiority or Other
OG000 OG003

Secondary

Number of Participants With Hypercalcemia

Occurrence of grade 3 or 4 hypercalcemia according to the Common Terminology Criteria for Adverse Events (CTCAE) v3. A summary of hypercalcemia events is reported under adverse events.

Posted

Number

Participants

Day 1 to Week 57

ID	Title	Description
OG000	Bisphosphonate IV Q4W	Open label bisphosphonate every 4 weeks (Q4W) by intravenous infusion
OG001	Denosumab 30 mg Q4W	Denosumab 30 mg by subcutaneous injection every 4 weeks (Q4W)
OG002	Denosumab 120 mg Q4W	Denosumab 120 mg by subcutaneous injection every 4 weeks (Q4W)
OG003	Denosumab 180 mg Q4W	Denosumab 180 mg by subcutaneous injection every 4 weeks (Q4W)
OG004	Denosumab 60 mg Q12W	Denosumab 60 mg by subcutaneous injection every 12 weeks (Q12W)
OG005	Denosumab 180 mg Q12W	Denosumab 180 mg by subcutaneous injection every 12 weeks (Q12W)

Units	Counts
Participants	OG00041 OG00141 OG00240 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0020 OG003