Trial Outcomes & Findings for Observational Study of Denosumab (Prolia®) in Postmenopausal Women With Osteoporosis (NCT NCT01668589)

NCT ID: NCT01668589

Last Updated: 2018-01-30

Results Overview

A participant was considered persistent with denosumab at 12 months if they received at least 1 denosumab injection following the pre-enrolment denosumab injection no later than 6 months + 8 weeks (ie, no greater than 239 days apart). A participant was considered persistent with denosumab at 24 months if they received at least 3 denosumab injections following the pre-enrolment denosumab injection, and the length of time between any 2 consecutive denosumab injections did not exceed 6 months + 8 weeks (ie, no greater than 239 days apart).

• Recruitment status: COMPLETED
• Target enrollment: 1501 participants
• Primary outcome timeframe: 12 months and 24 months
• Results posted on: 2018-01-30

Participant Flow

The study was conducted at various study centers in Germany, Austria, Greece, and Belgium. The recruitment period was from 28 November 2012 to 31 August 2013.

Participant milestones

Measure	Germany Participants in Germany who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Austria Participants in Austria who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Greece Participants in Greece who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Belgium Participants in Belgium who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.
Overall Study STARTED	600	300	300	301
Overall Study Received Denosumab	599	300	300	301
Overall Study COMPLETED	461	242	265	266
Overall Study NOT COMPLETED	139	58	35	35

Reasons for withdrawal

Measure	Germany Participants in Germany who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Austria Participants in Austria who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Greece Participants in Greece who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Belgium Participants in Belgium who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.
Overall Study Lost to Follow-up	29	37	15	5
Overall Study Full Consent/Agreement Withdrawn	54	8	11	4
Overall Study Death	12	3	2	11
Overall Study Other	44	10	7	15

Baseline Characteristics

Observational Study of Denosumab (Prolia®) in Postmenopausal Women With Osteoporosis

Baseline characteristics by cohort

Measure	Germany n=579 Participants Participants in Germany who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Austria n=300 Participants Participants in Austria who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Greece n=299 Participants Participants in Greece who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Belgium n=301 Participants Participants in Belgium who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Total n=1479 Participants Total of all reporting groups
Age, Continuous	72.5 years STANDARD_DEVIATION 8.7 • n=5 Participants	71.0 years STANDARD_DEVIATION 9.5 • n=7 Participants	66.3 years STANDARD_DEVIATION 9.2 • n=5 Participants	71.2 years STANDARD_DEVIATION 10.4 • n=4 Participants	70.7 years STANDARD_DEVIATION 9.6 • n=21 Participants
Sex: Female, Male Female	579 Participants n=5 Participants	300 Participants n=7 Participants	299 Participants n=5 Participants	301 Participants n=4 Participants	1479 Participants n=21 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: 12 months and 24 months

Population: Full analysis set

A participant was considered persistent with denosumab at 12 months if they received at least 1 denosumab injection following the pre-enrolment denosumab injection no later than 6 months + 8 weeks (ie, no greater than 239 days apart).

A participant was considered persistent with denosumab at 24 months if they received at least 3 denosumab injections following the pre-enrolment denosumab injection, and the length of time between any 2 consecutive denosumab injections did not exceed 6 months + 8 weeks (ie, no greater than 239 days apart).

Outcome measures

Measure	Germany n=579 Participants Participants in Germany who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Austria n=300 Participants Participants in Austria who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Greece n=299 Participants Participants in Greece who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Belgium n=301 Participants Participants in Belgium who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.
Percentage of Participants Persistent With Denosumab Injections at 12 Months and 24 Months 12 Months	92.2 percentage of participants Interval 89.7 to 94.3	89.3 percentage of participants Interval 85.3 to 92.6	94.3 percentage of participants Interval 91.1 to 96.7	95.7 percentage of participants Interval 92.7 to 97.7
Percentage of Participants Persistent With Denosumab Injections at 12 Months and 24 Months 24 Months	75.1 percentage of participants Interval 71.4 to 78.6	79.7 percentage of participants Interval 74.7 to 84.1	82.6 percentage of participants Interval 77.8 to 86.7	86.0 percentage of participants Interval 81.6 to 89.8

PRIMARY outcome

Timeframe: 12 months and 24 months

Population: Full analysis set

A participant was considered adherent to denosumab at 12 months if they received at least 1 denosumab injection over the 12-month period following the pre-enrolment denosumab injection, with the time between any 2 consecutive injections being at most 6 months ± 4 weeks (between 155 and 211 days apart).

A participant was considered adherent to denosumab at 24 months if they received at least 3 denosumab injections over the 24-month period following the pre-enrolment denosumab injection, with the time between any 2 consecutive injections being at most 6 months ± 4 weeks (between 155 and 211 days apart).

Outcome measures

Measure	Germany n=579 Participants Participants in Germany who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Austria n=300 Participants Participants in Austria who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Greece n=299 Participants Participants in Greece who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Belgium n=301 Participants Participants in Belgium who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.
Percentage of Participants Adherent to Denosumab Injection at 12 Months and 24 Months 12 Months	87.6 percentage of participants Interval 84.6 to 90.1	85.0 percentage of participants Interval 80.4 to 88.8	89.6 percentage of participants Interval 85.6 to 92.8	89.0 percentage of participants Interval 84.9 to 92.3
Percentage of Participants Adherent to Denosumab Injection at 12 Months and 24 Months 24 Months	62.9 percentage of participants Interval 58.8 to 66.8	66.0 percentage of participants Interval 60.3 to 71.3	69.6 percentage of participants Interval 64.0 to 74.7	70.1 percentage of participants Interval 64.6 to 75.2

PRIMARY outcome

Timeframe: From baseline to 12 months and 24 months

Population: Full analysis set

MCR at 12 months was defined as the accumulative number of days covered with denosumab treatment during the first 12 months divided by 366 days, expressed as a percentage.

MCR at 24 months was defined as the accumulative number of days covered with denosumab treatment during the first 24 months divided by 732 days, expressed as a percentage.

It was assumed that each injection of denosumab treatment provided 6 months of coverage (or 183 days) from the date of injection or until the date of the next injection, whichever comes first. So, a participant who received only 1 injection in the first year would have MCR at 12 months equal to 50%.

Outcome measures

Measure	Germany n=579 Participants Participants in Germany who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Austria n=300 Participants Participants in Austria who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Greece n=299 Participants Participants in Greece who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Belgium n=301 Participants Participants in Belgium who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.
Medication Coverage Ratio (MCR) for Denosumab Injection at 12 Months and 24 Months 12 Months	94.5 percentage of days of coverage Interval 93.5 to 95.5	93.2 percentage of days of coverage Interval 91.6 to 94.9	95.8 percentage of days of coverage Interval 94.6 to 96.9	96.2 percentage of days of coverage Interval 95.1 to 97.3
Medication Coverage Ratio (MCR) for Denosumab Injection at 12 Months and 24 Months 24 Months	87.4 percentage of days of coverage Interval 85.8 to 89.1	87.9 percentage of days of coverage Interval 85.3 to 90.4	91.2 percentage of days of coverage Interval 89.3 to 93.1	92.4 percentage of days of coverage Interval 90.5 to 94.2

SECONDARY outcome

Timeframe: 24 months

Population: Full analysis set who were non-persistent at 24 months

Time to non-persistence for non-persistent patients was calculated as the time between the date of the first denosumab injection and the date of last denosumab injection received during the period where the patient was still classified as persistent, plus 6 months (183 days). Participants were considered persistent at 24 months if they received at least 4 injections, including the baseline injection, with no more than 6 months + 8 weeks apart between any 2 consecutive injections.

Outcome measures

Measure	Germany n=144 Participants Participants in Germany who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Austria n=61 Participants Participants in Austria who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Greece n=52 Participants Participants in Greece who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Belgium n=42 Participants Participants in Belgium who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.
Time to Non-persistence With Denosumab Injection	12.23 months Interval 6.03 to 17.89	6.03 months Interval 6.03 to 13.05	12.00 months Interval 6.03 to 13.38	12.20 months Interval 6.03 to 17.51

SECONDARY outcome

Timeframe: 24 months

Population: Full analysis set

The percentage of participants who received 0, 1, 2, or 3 denosumab injections within the specified window (defined by the persistence definition as 6 months + 8 weeks). The number of injections that a participant took during the 2-year period after the first pre-enrolment injection, and that were given within the appropriate window from the previous injection, irrespective of when the previous injection was given. Only the first 3 post-baseline injections are considered.

Outcome measures

Measure	Germany n=579 Participants Participants in Germany who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Austria n=300 Participants Participants in Austria who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Greece n=299 Participants Participants in Greece who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Belgium n=301 Participants Participants in Belgium who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.
Percentage of Participants Who Received Denosumab Injections Within the Specified Window 3 post-baseline injections	75.1 percentage of participants	79.7 percentage of participants	82.6 percentage of participants	86.0 percentage of participants
Percentage of Participants Who Received Denosumab Injections Within the Specified Window No post-baseline injections	5.9 percentage of participants 0.9 • Interval 6.03 to 17.89	9.7 percentage of participants 0.9 • Interval 6.03 to 13.05	2.7 percentage of participants 0.7 • Interval 6.03 to 13.38	3.7 percentage of participants 0.7 • Interval 6.03 to 17.51
Percentage of Participants Who Received Denosumab Injections Within the Specified Window 1 post-baseline injection	7.8 percentage of participants	3.7 percentage of participants	7.0 percentage of participants	3.0 percentage of participants
Percentage of Participants Who Received Denosumab Injections Within the Specified Window 2 post-baseline injections	11.2 percentage of participants	7.0 percentage of participants	7.7 percentage of participants	7.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: Full analysis set with a baseline value and a month 24 value measured with the same machine type.

Bone mineral density was measured using dual energy X-ray absorptiometry (DXA).

Outcome measures

Measure	Germany n=100 Participants Participants in Germany who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Austria n=28 Participants Participants in Austria who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Greece n=10 Participants Participants in Greece who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Belgium n=31 Participants Participants in Belgium who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.
Percent Change From Baseline in Total Hip Bone Mineral Density (BMD) at 24 Months	4.4 percent change Standard Deviation 6.2	4.1 percent change Standard Deviation 3.2	6.6 percent change Standard Deviation 6.6	4.1 percent change Standard Deviation 6.3

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: Full analysis set with a baseline value and a month 24 value measured with the same body side and machine type.

Bone mineral density was measured using dual energy X-ray absorptiometry (DXA).

Outcome measures

Measure	Germany n=116 Participants Participants in Germany who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Austria n=28 Participants Participants in Austria who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Greece n=29 Participants Participants in Greece who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Belgium n=31 Participants Participants in Belgium who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.
Percent Change From Baseline in Femoral Neck Bone Mineral Density (BMD) at 24 Months	3.4 percent change Standard Deviation 5.4	3.7 percent change Standard Deviation 5.7	6.0 percent change Standard Deviation 9.5	3.1 percent change Standard Deviation 9.3

SECONDARY outcome

Timeframe: Baseline and Month 24

Population: Full analysis set with a baseline value and a month 24 value measured with the same machine type.

Bone mineral density was measured using dual energy X-ray absorptiometry (DXA).

Outcome measures

Measure	Germany n=131 Participants Participants in Germany who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Austria n=24 Participants Participants in Austria who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Greece n=57 Participants Participants in Greece who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.	Belgium n=34 Participants Participants in Belgium who received denosumab 60 mg once every 6 months subcutaneously according to the approved prescribing information for the treatment of postmenopausal osteoporosis (PMO) in routine clinical practice.
Percent Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at 24 Months	6.5 percent change Standard Deviation 6.2	8.2 percent change Standard Deviation 4.6	8.4 percent change Standard Deviation 8.3	7.8 percent change Standard Deviation 5.9

Adverse Events

Germany

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Austria

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Greece

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Belgium

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Germany n=579 participants at risk Prolia 60 mg SC Q6M	Austria n=300 participants at risk Prolia 60 mg SC Q6M	Greece n=300 participants at risk Prolia 60 mg SC Q6M	Belgium n=301 participants at risk Prolia 60 mg SC Q6M
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/579 • 24 months Only adverse drug reactions were collected in this observational study. Serious Adverse Events summarizes serious adverse drug reactions, defined as serious adverse events that are considered related to denosumab. Other Adverse Events summarizes the non-serious occurrences of adverse drug reactions that exceeded a 1% frequency threshold.	0.00% 0/300 • 24 months Only adverse drug reactions were collected in this observational study. Serious Adverse Events summarizes serious adverse drug reactions, defined as serious adverse events that are considered related to denosumab. Other Adverse Events summarizes the non-serious occurrences of adverse drug reactions that exceeded a 1% frequency threshold.	0.00% 0/300 • 24 months Only adverse drug reactions were collected in this observational study. Serious Adverse Events summarizes serious adverse drug reactions, defined as serious adverse events that are considered related to denosumab. Other Adverse Events summarizes the non-serious occurrences of adverse drug reactions that exceeded a 1% frequency threshold.	0.33% 1/301 • 24 months Only adverse drug reactions were collected in this observational study. Serious Adverse Events summarizes serious adverse drug reactions, defined as serious adverse events that are considered related to denosumab. Other Adverse Events summarizes the non-serious occurrences of adverse drug reactions that exceeded a 1% frequency threshold.
Musculoskeletal and connective tissue disorders Osteonecrosis of jaw	0.35% 2/579 • 24 months Only adverse drug reactions were collected in this observational study. Serious Adverse Events summarizes serious adverse drug reactions, defined as serious adverse events that are considered related to denosumab. Other Adverse Events summarizes the non-serious occurrences of adverse drug reactions that exceeded a 1% frequency threshold.	0.00% 0/300 • 24 months Only adverse drug reactions were collected in this observational study. Serious Adverse Events summarizes serious adverse drug reactions, defined as serious adverse events that are considered related to denosumab. Other Adverse Events summarizes the non-serious occurrences of adverse drug reactions that exceeded a 1% frequency threshold.	0.00% 0/300 • 24 months Only adverse drug reactions were collected in this observational study. Serious Adverse Events summarizes serious adverse drug reactions, defined as serious adverse events that are considered related to denosumab. Other Adverse Events summarizes the non-serious occurrences of adverse drug reactions that exceeded a 1% frequency threshold.	0.00% 0/301 • 24 months Only adverse drug reactions were collected in this observational study. Serious Adverse Events summarizes serious adverse drug reactions, defined as serious adverse events that are considered related to denosumab. Other Adverse Events summarizes the non-serious occurrences of adverse drug reactions that exceeded a 1% frequency threshold.

Other adverse events

Adverse event data not reported

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