Trial Outcomes & Findings for Safety and Efficacy Study to Evaluate Denosumab Compared With Zoledronic Acid in Postmenopausal Women With Osteoporosis (NCT NCT01732770)

Last Updated: 2020-03-10

Results Overview

Bone mineral density (BMD) of the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging facility.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

643 participants

Primary outcome timeframe

Baseline and Month 12

Results posted on

2020-03-10

Participant Flow

This study was conducted at 37 centers in Belgium, Denmark, Poland, Spain, Canada, United States of America, and Australia. The first participant enrolled on 07 November 2012 and the last participant enrolled on 15 January 2014.

Participants were randomized in a 1:1 allocation ratio to receive either denosumab or zoledronic acid. Randomization was stratified by screening serum type I collagen C-telopeptide (sCTX) values (\< 0.3 ng/mL, 0.3 to 0.5 ng/mL).

Participant milestones

Participant milestones
Measure	Zoledronic Acid 5 mg Q12M Participants received zoledronic acid 5 mg by intravenous infusion once every 12 months (Q12M) on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg Q6M Participants received denosumab 60 mg subcutaneous injection once every 6 months (Q6M) for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1.
Overall Study STARTED	322	321
Overall Study Received Study Treatment	320	320
Overall Study COMPLETED	312	313
Overall Study NOT COMPLETED	10	8

Reasons for withdrawal

Reasons for withdrawal
Measure	Zoledronic Acid 5 mg Q12M Participants received zoledronic acid 5 mg by intravenous infusion once every 12 months (Q12M) on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg Q6M Participants received denosumab 60 mg subcutaneous injection once every 6 months (Q6M) for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1.
Overall Study Lost to Follow-up	2	3
Overall Study Withdrawal by Subject	5	3
Overall Study Decision by Sponsor	2	2
Overall Study Death	1	0

Baseline Characteristics

Safety and Efficacy Study to Evaluate Denosumab Compared With Zoledronic Acid in Postmenopausal Women With Osteoporosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Zoledronic Acid 5 mg Q12M n=322 Participants Participants received zoledronic acid 5 mg by intravenous infusion once every 12 months (Q12M) on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg Q6M n=321 Participants Participants received denosumab 60 mg subcutaneous injection once every 6 months (Q6M) for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1.	Total n=643 Participants Total of all reporting groups
Age, Continuous	69.5 years STANDARD_DEVIATION 7.7 • n=5 Participants	68.5 years STANDARD_DEVIATION 7.1 • n=7 Participants	69.0 years STANDARD_DEVIATION 7.4 • n=5 Participants
Sex: Female, Male Female	322 Participants n=5 Participants	321 Participants n=7 Participants	643 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	314 participants n=5 Participants	309 participants n=7 Participants	623 participants n=5 Participants
Race/Ethnicity, Customized Asian	4 participants n=5 Participants	5 participants n=7 Participants	9 participants n=5 Participants
Race/Ethnicity, Customized Other	2 participants n=5 Participants	4 participants n=7 Participants	6 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Black or African American	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Multiple	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Screening serum CTX < 0.3 ng/mL	242 participants n=5 Participants	239 participants n=7 Participants	481 participants n=5 Participants
Screening serum CTX ≥ 0.3 ng/mL	78 participants n=5 Participants	82 participants n=7 Participants	160 participants n=5 Participants
Screening serum CTX Missing	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Lumbar Spine Bone Mineral Density (BMD) T-score	-2.64 T-score STANDARD_DEVIATION 0.86 • n=5 Participants	-2.74 T-score STANDARD_DEVIATION 0.83 • n=7 Participants	-2.69 T-score STANDARD_DEVIATION 0.84 • n=5 Participants
Total Hip BMD T-score	-1.93 T-score STANDARD_DEVIATION 0.80 • n=5 Participants	-1.93 T-score STANDARD_DEVIATION 0.74 • n=7 Participants	-1.93 T-score STANDARD_DEVIATION 0.77 • n=5 Participants
Femoral Neck BMD T-score	-2.17 T-score STANDARD_DEVIATION 0.68 • n=5 Participants	-2.17 T-score STANDARD_DEVIATION 0.66 • n=7 Participants	-2.17 T-score STANDARD_DEVIATION 0.67 • n=5 Participants
Prior Oral Bisphosphonate Duration	6.35 years STANDARD_DEVIATION 3.68 • n=5 Participants	6.21 years STANDARD_DEVIATION 3.84 • n=7 Participants	6.28 years STANDARD_DEVIATION 3.76 • n=5 Participants
Historical Fractures Any prior fracture	159 participants n=5 Participants	169 participants n=7 Participants	328 participants n=5 Participants
Historical Fractures Prior osteoporotic fracture	121 participants n=5 Participants	120 participants n=7 Participants	241 participants n=5 Participants
Body Mass Index (BMI)	24.31 kg/m² STANDARD_DEVIATION 4.18 • n=5 Participants	24.27 kg/m² STANDARD_DEVIATION 3.99 • n=7 Participants	24.29 kg/m² STANDARD_DEVIATION 4.08 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Month 12

Population: The primary efficacy analysis set includes all randomized participants who have a baseline BMD measurement and at least one postbaseline BMD measurement. Any postbaseline BMD value obtained at the early termination visit was carried forward as the month 12 value (ie, last observation carried forward \[LOCF\]).

Bone mineral density (BMD) of the lumbar spine was measured by dual-energy x-ray absorptiometry (DXA). DXA scans were analyzed by a central imaging facility.

Outcome measures

Outcome measures
Measure	Zoledronic Acid 5 mg Q12M n=312 Participants Participants received zoledronic acid 5 mg by intravenous infusion once every 12 months (Q12M) on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg Q6M n=314 Participants Participants received denosumab 60 mg subcutaneous injection once every 6 months (Q6M) for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1.
Percent Change From Baseline in Lumbar Spine Bone Mineral Density at Month 12 - Non-inferiority Analysis	1.1 percent change Interval 0.7 to 1.5	3.2 percent change Interval 2.8 to 3.6

SECONDARY outcome

Timeframe: Baseline and Month 12

Population: The primary efficacy analysis set; any postbaseline BMD value obtained at the early termination visit was carried forward as the month 12 value (ie, LOCF).

BMD of the hip was measured by DXA. DXA scans were analyzed by a central imaging facility.

Outcome measures

Outcome measures
Measure	Zoledronic Acid 5 mg Q12M n=309 Participants Participants received zoledronic acid 5 mg by intravenous infusion once every 12 months (Q12M) on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg Q6M n=311 Participants Participants received denosumab 60 mg subcutaneous injection once every 6 months (Q6M) for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1.
Percent Change From Baseline in Total Hip BMD at Month 12 - Non-inferiority Analysis	0.6 percent change Interval 0.3 to 0.8	1.9 percent change Interval 1.7 to 2.2

SECONDARY outcome

Timeframe: Baseline and Month 12

Population: The primary efficacy analysis set; any postbaseline BMD value obtained at the early termination visit was carried forward as the month 12 value (ie, LOCF).

Outcome measures

Outcome measures
Measure	Zoledronic Acid 5 mg Q12M n=312 Participants Participants received zoledronic acid 5 mg by intravenous infusion once every 12 months (Q12M) on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg Q6M n=314 Participants Participants received denosumab 60 mg subcutaneous injection once every 6 months (Q6M) for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1.
Percent Change From Baseline in Lumbar Spine BMD at Month 12 - Superiority Analysis	1.1 percent change Interval 0.7 to 1.5	3.2 percent change Interval 2.8 to 3.6

SECONDARY outcome

Timeframe: Baseline and Month 12

Population: The primary efficacy analysis set; any postbaseline BMD value obtained at the early termination visit was carried forward as the month 12 value (ie, LOCF).

Outcome measures

Outcome measures
Measure	Zoledronic Acid 5 mg Q12M n=309 Participants Participants received zoledronic acid 5 mg by intravenous infusion once every 12 months (Q12M) on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg Q6M n=311 Participants Participants received denosumab 60 mg subcutaneous injection once every 6 months (Q6M) for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1.
Percent Change From Baseline in Total Hip BMD at Month 12 - Superiority Analysis	0.6 percent change Interval 0.3 to 0.8	1.9 percent change Interval 1.7 to 2.2

Adverse Events

Zoledronic Acid 5 mg Q12M

Serious events: 29 serious events

Other events: 22 other events

Deaths: 0 deaths

Denosumab 60 mg Q6M

Serious events: 25 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Zoledronic Acid 5 mg Q12M n=320 participants at risk Participants received zoledronic acid 5 mg by intravenous infusion once every 12 months (Q12M) on Day 1 and placebo to denosumab by subcutaneous injection on Day 1 and at Month 6.	Denosumab 60 mg Q6M n=320 participants at risk Participants received denosumab 60 mg subcutaneous injection once every 6 months (Q6M) for 12 months and placebo to zoledronic acid by intravenous infusion on Day 1.
Musculoskeletal and connective tissue disorders Arthralgia	6.9% 22/320 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.	4.7% 15/320 • 12 months Other Adverse Events summarizes the non-serious occurrences of adverse events that exceed the indicated frequency threshold.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER