Trial Outcomes & Findings for Denosumab Adherence Preference Satisfaction Study (NCT NCT00518531)

Results Overview

A participant was considered adherent to denosumab treatment if the participant: - received 2 denosumab injections (overall treatment compliance); - took each injection 6 months (± 4 weeks) apart (treatment compliance over time); - completed the relevant treatment period (treatment persistence). A participant was considered adherent to alendronate treatment if the participant: - took ≥ 80% QW tablets (overall treatment compliance); - took at least 2 tablets in the last month and completed the relevant treatment period (treatment persistence). Participants who did not meet all criteria for their assigned treatment were deemed non-adherent to treatment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

250 participants

Primary outcome timeframe

Treatment period 1 (Month 1 to Month 12)

Results posted on

2019-12-03

Participant Flow

First subject enrolled 03-Oct-07, last subject enrolled 25-Jun-08; First subject crossovered 22-May-08, last subject crossovered 25-Jun-09;

Participant milestones

Participant milestones
Measure	Alendronate in Period 1 Then Denosumab in Period 2 Alendronate 70 mg orally once a week (QW) for 1 year (treatment period 1) followed by Denosumab 60 mg subcutaneously every 6 months for 1 year (treatment period 2).	Denosumab in Period 1 Then Alendronate in Period 2 Denosumab 60 mg subcutaneously every 6 months for 1 year (treatment period 1) followed by Alendronate 70 mg orally once a week for 1 year (treatment period 2).
Treatment Period 1 STARTED	124	126
Treatment Period 1 Received Treatment	119	124
Treatment Period 1 COMPLETED	106	114
Treatment Period 1 NOT COMPLETED	18	12
Treatment Period 2 STARTED	106	115
Treatment Period 2 Received Treatment	106	110
Treatment Period 2 COMPLETED	103	95
Treatment Period 2 NOT COMPLETED	3	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Alendronate in Period 1 Then Denosumab in Period 2 Alendronate 70 mg orally once a week (QW) for 1 year (treatment period 1) followed by Denosumab 60 mg subcutaneously every 6 months for 1 year (treatment period 2).	Denosumab in Period 1 Then Alendronate in Period 2 Denosumab 60 mg subcutaneously every 6 months for 1 year (treatment period 1) followed by Alendronate 70 mg orally once a week for 1 year (treatment period 2).
Treatment Period 1 Adverse Event	5	0
Treatment Period 1 Lost to Follow-up	5	3
Treatment Period 1 Physician Decision	1	0
Treatment Period 1 Protocol Violation	2	0
Treatment Period 1 Withdrawal by Subject	4	6
Treatment Period 1 Early crossover	1	3
Treatment Period 2 Withdrawal by Subject	0	8
Treatment Period 2 Complete out of scheduled visit window	1	2
Treatment Period 2 Adverse Event	1	7
Treatment Period 2 Protocol-specified criteria	0	1
Treatment Period 2 Non-compliance	1	2

Baseline Characteristics

Denosumab Adherence Preference Satisfaction Study

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Alendronate in Period 1 Then Denosumab in Period 2 n=124 Participants Alendronate 70 mg orally once a week for 1 year (treatment period 1) followed by Denosumab 60 mg subcutaneously every 6 months for 1 year (treatment period 2).	Denosumab in Period 1 Then Alendronate in Period 2 n=126 Participants Denosumab 60 mg subcutaneously every 6 months for 1 year (treatment period 1) followed by Alendronate 70 mg orally once a week for 1 year (treatment period 2).	Total n=250 Participants Total of all reporting groups
Age, Continuous	65.3 Years STANDARD_DEVIATION 7.7 • n=39 Participants	65.1 Years STANDARD_DEVIATION 7.6 • n=41 Participants	65.2 Years STANDARD_DEVIATION 7.6 • n=35 Participants
Sex: Female, Male Female	124 Participants n=39 Participants	126 Participants n=41 Participants	250 Participants n=35 Participants
Sex: Female, Male Male	0 Participants n=39 Participants	0 Participants n=41 Participants	0 Participants n=35 Participants
Race/Ethnicity, Customized White or Caucasian	119 Participants n=39 Participants	115 Participants n=41 Participants	234 Participants n=35 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=39 Participants	2 Participants n=41 Participants	4 Participants n=35 Participants
Race/Ethnicity, Customized Hispanic or Latino	1 Participants n=39 Participants	6 Participants n=41 Participants	7 Participants n=35 Participants
Race/Ethnicity, Customized Asian	1 Participants n=39 Participants	3 Participants n=41 Participants	4 Participants n=35 Participants
Race/Ethnicity, Customized Japanese	1 Participants n=39 Participants	0 Participants n=41 Participants	1 Participants n=35 Participants

PRIMARY outcome

Timeframe: Treatment period 1 (Month 1 to Month 12)

Population: The full analysis set (FAS) includes all participants who were randomized.

A participant was considered adherent to denosumab treatment if the participant: - received 2 denosumab injections (overall treatment compliance); - took each injection 6 months (± 4 weeks) apart (treatment compliance over time); - completed the relevant treatment period (treatment persistence). A participant was considered adherent to alendronate treatment if the participant: - took ≥ 80% QW tablets (overall treatment compliance); - took at least 2 tablets in the last month and completed the relevant treatment period (treatment persistence). Participants who did not meet all criteria for their assigned treatment were deemed non-adherent to treatment.

Outcome measures

Outcome measures
Measure	Alendronate n=124 Participants Participants received alendronate 70 mg orally once a week for 1 year.	Denosumab n=126 Participants Participants received denosumab 60 mg subcutaneously every 6 months for 1 year.
Adherence With Treatment in the First Treatment Period Yes	95 Participants	111 Participants
Adherence With Treatment in the First Treatment Period No	29 Participants	15 Participants

SECONDARY outcome

Timeframe: Treatment period 2 (Months 13 to 24)

Population: The cross-over analysis set includes all participants who crossed over to their treatment period 2 treatment.

A participant was considered adherent to denosumab treatment if the participant: - received 2 denosumab injections (overall treatment compliance); - took each injection 6 months (± 4 weeks) apart (treatment compliance over time); - completed the relevant treatment period (treatment persistence). A participant was considered adherent to alendronate treatment if the participant: - took ≥ 80% QW tablets (overall treatment compliance); - took at least 2 tablets in the last month and completed the relevant treatment period (treatment persistence). Participants who did not meet all criteria for their assigned treatment were deemed nonadherent to treatment.

Outcome measures

Outcome measures
Measure	Alendronate n=115 Participants Participants received alendronate 70 mg orally once a week for 1 year.	Denosumab n=106 Participants Participants received denosumab 60 mg subcutaneously every 6 months for 1 year.
Adherence With Treatment in the Second Treatment Period Yes	73 Participants	98 Participants
Adherence With Treatment in the Second Treatment Period No	42 Participants	8 Participants

SECONDARY outcome

Timeframe: Treatment period 1 (Month 1 to Month 12)

Population: Full analysis set

Participants were considered compliant to denosumab treatment if they received 2 denosumab injections (overall treatment compliance) and if they took each injection 6 months (± 4 weeks) apart (treatment compliance over time). Participants were considered compliant to alendronate treatment if they took ≥ 80% QW tablets (overall treatment compliance).

Outcome measures

Outcome measures
Measure	Alendronate n=124 Participants Participants received alendronate 70 mg orally once a week for 1 year.	Denosumab n=126 Participants Participants received denosumab 60 mg subcutaneously every 6 months for 1 year.
Compliance With Treatment in the First Treatment Period Yes	97 Participants	114 Participants
Compliance With Treatment in the First Treatment Period No	27 Participants	12 Participants

SECONDARY outcome

Timeframe: Treatment period 2 (Month 13 to Month 24)

Population: Crossover set

Participants were considered compliant to denosumab treatment if they received 2 denosumab injections (overall treatment compliance) and if they took each injection 6 months (± 4 weeks) apart (treatment compliance over time). Participants were considered compliant to alendronate treatment if they took ≥ 80% QW tablets (overall treatment compliance).

Outcome measures

Outcome measures
Measure	Alendronate n=115 Participants Participants received alendronate 70 mg orally once a week for 1 year.	Denosumab n=106 Participants Participants received denosumab 60 mg subcutaneously every 6 months for 1 year.
Compliance With Treatment in the Second Treatment Period Yes	78 Participants	99 Participants
Compliance With Treatment in the Second Treatment Period No	37 Participants	7 Participants

SECONDARY outcome

Timeframe: Treatment period 1 (Month 1 to Month 12)

Population: Full analysis set

Denosumab-treated participants were considered persistent to treatment if they completed the relevant treatment period and alendronate-treated participants were considered persistent to treatment if they completed the relevant treatment period and took at least 2 tablets in the last month of the treatment period.

Outcome measures

Outcome measures
Measure	Alendronate n=124 Participants Participants received alendronate 70 mg orally once a week for 1 year.	Denosumab n=126 Participants Participants received denosumab 60 mg subcutaneously every 6 months for 1 year.
Persistence With Treatment in the First Treatment Period Yes	99 Participants	114 Participants
Persistence With Treatment in the First Treatment Period No	25 Participants	12 Participants

SECONDARY outcome

Timeframe: Treatment period 2 (Month 13 to Month 24)

Population: Crossover set

Denosumab-treated participants were considered persistent to treatment if they completed the relevant treatment period and alendronate-treated participants were considered persistent to treatment if they completed the relevant treatment period and took at least 2 tablets in the last month of the treatment period.

Outcome measures

Outcome measures
Measure	Alendronate n=115 Participants Participants received alendronate 70 mg orally once a week for 1 year.	Denosumab n=106 Participants Participants received denosumab 60 mg subcutaneously every 6 months for 1 year.
Persistence With Treatment in the Second Treatment Period Yes	82 Participants	103 Participants
Persistence With Treatment in the Second Treatment Period No	33 Participants	3 Participants

SECONDARY outcome

Timeframe: Treatment Period 1 (Month 1 to Month 12)

Population: Full analysis set

Time to treatment non-adherence for alendronate is defined for each treatment period as the time to treatment non-compliance or time to treatment non-persistence, whichever occurs earliest, for participants with uncensored values. Participants who had both censored time to non-compliance and censored time to non-persistence values were censored in the analysis at the end of treatment period visit.

Outcome measures

Outcome measures
Measure	Alendronate n=124 Participants Participants received alendronate 70 mg orally once a week for 1 year.	Denosumab Participants received denosumab 60 mg subcutaneously every 6 months for 1 year.
Time to Non-adherence to Alendronate Treatment in the First Treatment Period	43.29 weeks Standard Error 1.46	—

SECONDARY outcome

Timeframe: Treatment Period 2 (Month 13 to Month 24)

Population: Crossover set

Time to treatment non-adherence for alendronate is defined for each treatment period as the time to treatment non-compliance or time to treatment non-persistence, whichever occurs earliest, for participants with uncensored values. Participants who had both censored time to non-compliance and censored time to non-persistence values were censored in the analysis at the end of treatment period visit.

Outcome measures

Outcome measures
Measure	Alendronate n=115 Participants Participants received alendronate 70 mg orally once a week for 1 year.	Denosumab Participants received denosumab 60 mg subcutaneously every 6 months for 1 year.
Time to Non-adherence to Alendronate Treatment in the Second Treatment Period	39.45 weeks Standard Error 1.89	—

SECONDARY outcome

Timeframe: Treatment period 1 (Month 1 to Month 12)

Population: Full analysis set

Time to treatment non-compliance for alendronate is based on the percent of QW tablets taken and is defined for each treatment period as the first week since Study Day 1 of the treatment period to the week where the percent of QW tablets taken falls below the threshold of ≥ 80% and where the participant can not reach this threshold again during the treatment period.

Outcome measures

Outcome measures
Measure	Alendronate n=124 Participants Participants received alendronate 70 mg orally once a week for 1 year.	Denosumab Participants received denosumab 60 mg subcutaneously every 6 months for 1 year.
Time to Non-compliance to Alendronate Treatment in the First Treatment Period	43.75 weeks Standard Error 1.42	—

SECONDARY outcome

Timeframe: Treatment period 2 (Month 13 to Month 24)

Population: crossover set

Time to treatment non-compliance for alendronate is based on the percent of QW tablets taken and is defined for each treatment period as the first week since Study Day 1 of the treatment period to the week where the percent of QW tablets taken falls below the threshold of ≥ 80% and where the participant can not reach this threshold again during the treatment period.

Outcome measures

Outcome measures
Measure	Alendronate n=115 Participants Participants received alendronate 70 mg orally once a week for 1 year.	Denosumab Participants received denosumab 60 mg subcutaneously every 6 months for 1 year.
Time to Non-compliance to Alendronate Treatment in the Second Treatment Period	39.97 weeks Standard Error 1.87	—

SECONDARY outcome

Timeframe: Treatment period 1 (Month 1 to Month 12)

Population: Full analysis set

Time to non-persistence for alendronate is defined for each treatment period as the first time \<2 tablets were taken in a rolling 4-week time period (e.g. study weeks 1-4, 2-5, 3-6 etc) and where the participant never reaches this threshold again during the treatment period. Tablet intake was tracked using a Medication Event Monitoring System.

Outcome measures

Outcome measures
Measure	Alendronate n=124 Participants Participants received alendronate 70 mg orally once a week for 1 year.	Denosumab Participants received denosumab 60 mg subcutaneously every 6 months for 1 year.
Time to Non-persistence to Alendronate Treatment in the First Treatment Period	44.59 weeks Standard Error 1.35	—

SECONDARY outcome

Timeframe: Treatment period 2 (Month 13 to Month 24)

Population: Crossover set

Time to non-persistence for alendronate is defined for each treatment period as the first time \<2 tablets were taken in a rolling 4-week time period (e.g. study weeks 1-4, 2-5, 3-6 etc) and where the participant never reaches this threshold again during the treatment period. Tablet intake was tracked using a Medication Event Monitoring System.

Outcome measures

Outcome measures
Measure	Alendronate n=115 Participants Participants received alendronate 70 mg orally once a week for 1 year.	Denosumab Participants received denosumab 60 mg subcutaneously every 6 months for 1 year.
Time to Non-persistence to Alendronate Treatment in the Second Treatment Period	42.76 weeks Standard Error 1.69	—

SECONDARY outcome

Timeframe: End of treatment period 1 (Month 12)

Population: The Patient Reported Outcomes (PRO) analysis set for each independent treatment period included patients in the FAS who received at least one dose of study drug and had at least one post-baseline assessment in the relevant treatment period. Analysis population includes patients with observed data for ≥1 question in the questionnaire.

Participant satisfaction with their treatment was assessed using question 7 (ie, "Please rate your satisfaction with the weekly pill on the following: frequency of administration; mode of administration \[taking a pill\]; convenience; overall satisfaction") and question 8 (ie, "Please rate your satisfaction with the six month injection on the following: frequency of administration; mode of administration \[receiving an injection\]; convenience; overall satisfaction") from the Preference Satisfaction Questionnaire (PSQ) at the end of each treatment period. The PSQ is a 34 item, self-report questionnaire of participants' preference and satisfaction for each of the two study treatments. Possible answers include: "Not at all Satisfied", "A Little Satisfied", "Moderately Satisfied", "Quite Satisfied", and "Very Satisfied".

Outcome measures

Outcome measures
Measure	Alendronate n=114 Participants Participants received alendronate 70 mg orally once a week for 1 year.	Denosumab n=121 Participants Participants received denosumab 60 mg subcutaneously every 6 months for 1 year.
Overall Satisfaction to Study Treatment Not at all satisfied	3 Participants	3 Participants
Overall Satisfaction to Study Treatment A little satisfied	1 Participants	3 Participants
Overall Satisfaction to Study Treatment Moderately satisfied	17 Participants	2 Participants
Overall Satisfaction to Study Treatment Quite satisfied	34 Participants	18 Participants
Overall Satisfaction to Study Treatment Very satisfied	59 Participants	95 Participants

SECONDARY outcome

Timeframe: Baseline, Month 6, Month 12, Month 18 and Month 24

Population: Participants in the PRO analysis set with observed data; "n" indicates the number of patients with available data at each time point.

The BMQ is a 22- item self-reported questionnaire specific to osteoporosis that measures beliefs about the weekly pill or every 6 months injection. The BMQ consists of 3 subscales measuring beliefs about the necessity of the medication for controlling osteoporosis, concern with the adverse consequences of taking the medication, and preference for one medication over the other. Participants' beliefs about the necessity of the prescribed medication to treat osteoporosis were based on the average of 5 items from the BMQ that form the necessity score. The necessity score ranges from 1 to 5, with higher scores indicating stronger beliefs about the necessity of the prescribed medication for controlling osteoporosis.

Outcome measures

Outcome measures
Measure	Alendronate n=115 Participants Participants received alendronate 70 mg orally once a week for 1 year.	Denosumab n=121 Participants Participants received denosumab 60 mg subcutaneously every 6 months for 1 year.
Beliefs About Medicines Questionnaire (BMQ): Necessity Score Baseline (n=104, 117)	3.32 scores on a scale Standard Deviation 0.52	3.26 scores on a scale Standard Deviation 0.48
Beliefs About Medicines Questionnaire (BMQ): Necessity Score Month 6 (n=106, 114)	3.14 scores on a scale Standard Deviation 0.53	3.31 scores on a scale Standard Deviation 0.60
Beliefs About Medicines Questionnaire (BMQ): Necessity Score Month 12 (n=103, 95)	3.21 scores on a scale Standard Deviation 0.51	3.17 scores on a scale Standard Deviation 0.52
Beliefs About Medicines Questionnaire (BMQ): Necessity Score Month 18 (n=98, 98)	3.20 scores on a scale Standard Deviation 0.53	3.28 scores on a scale Standard Deviation 0.55
Beliefs About Medicines Questionnaire (BMQ): Necessity Score Month 24 (n=91, 100)	3.21 scores on a scale Standard Deviation 0.62	3.22 scores on a scale Standard Deviation 0.58

SECONDARY outcome

Timeframe: Baseline and Month 6, Month 12, Month 18, and Month 24

Population: Participants in the PRO analysis set with observed data; "n" indicates the number of patients with available data at each time point.

The BMQ is a 22- item self-reported questionnaire specific to osteoporosis that measures beliefs about the weekly pill or every 6 months injection. The BMQ consists of 3 subscales measuring beliefs about the necessity of the medication for controlling osteoporosis, concern with the adverse consequences of taking the medication, and preference for one medication over the other. Participants' concern about the adverse consequences of taking the medication for controlling osteoporosis was based on the average of 10 items from the BMQ that form the concern score. The concern score ranges from 1 to 5, with higher scores indicating stronger concerns about the adverse consequences of taking the prescribed medication for controlling osteoporosis.

Outcome measures

Outcome measures
Measure	Alendronate n=115 Participants Participants received alendronate 70 mg orally once a week for 1 year.	Denosumab n=121 Participants Participants received denosumab 60 mg subcutaneously every 6 months for 1 year.
Beliefs About Medicines Questionnaire (BMQ) Concern Score Baseline (n=104, 117)	2.33 scores on a scale Standard Deviation 0.48	2.43 scores on a scale Standard Deviation 0.46
Beliefs About Medicines Questionnaire (BMQ) Concern Score Month 6 (n=106, 114)	2.22 scores on a scale Standard Deviation 0.51	2.12 scores on a scale Standard Deviation 0.51
Beliefs About Medicines Questionnaire (BMQ) Concern Score Month 12 (n=103, 95)	2.57 scores on a scale Standard Deviation 0.48	2.51 scores on a scale Standard Deviation 0.50
Beliefs About Medicines Questionnaire (BMQ) Concern Score Month 18 (n=98, 98)	2.43 scores on a scale Standard Deviation 0.58	2.24 scores on a scale Standard Deviation 0.49
Beliefs About Medicines Questionnaire (BMQ) Concern Score Month 24 (n=91, 100)	2.39 scores on a scale Standard Deviation 0.58	2.18 scores on a scale Standard Deviation 0.51

SECONDARY outcome

Timeframe: Baseline and Month 6, Month 12, Month 18, and Month 24

Population: Participants in the PRO analysis set with observed data; "n" indicates the number of patients with available data at each time point.

The BMQ is a 22- item self-reported questionnaire specific to osteoporosis that measures beliefs about the weekly pill or every 6 months injection. The BMQ consists of 3 subscales measuring beliefs about the necessity of the medication for controlling osteoporosis, concern with the adverse consequences of taking the medication, and preference for one medication over the other. The BMQ preference score, which measures a participant's overall evaluation of a medication, is based on the average of 7 items in the BMQ. The preference score ranges from 1 to 5, with higher scores indicating stronger preference for one medication over the other.

Outcome measures

Outcome measures
Measure	Alendronate n=115 Participants Participants received alendronate 70 mg orally once a week for 1 year.	Denosumab n=121 Participants Participants received denosumab 60 mg subcutaneously every 6 months for 1 year.
Beliefs About Medicines Questionnaire (BMQ) Preference Score Baseline (n=104, 117)	2.97 scores on a scale Standard Deviation 0.40	3.47 scores on a scale Standard Deviation 0.43
Beliefs About Medicines Questionnaire (BMQ) Preference Score Month 6 (n=106, 114)	3.01 scores on a scale Standard Deviation 0.53	3.72 scores on a scale Standard Deviation 0.47
Beliefs About Medicines Questionnaire (BMQ) Preference Score Month 12 (n=103, 95)	2.62 scores on a scale Standard Deviation 0.50	3.43 scores on a scale Standard Deviation 0.45
Beliefs About Medicines Questionnaire (BMQ) Preference Score Month 18 (n=98, 98)	2.55 scores on a scale Standard Deviation 0.56	3.77 scores on a scale Standard Deviation 0.47
Beliefs About Medicines Questionnaire (BMQ) Preference Score Month 24 (n=91, 100)	2.57 scores on a scale Standard Deviation 0.65	3.80 scores on a scale Standard Deviation 0.52

SECONDARY outcome

Timeframe: Month 6, Month 12 (treatment period 1)

Population: Participants in the PRO analysis set with observed data; "n" indicates the number of patients with available data at each time point.

The MARs questionnaire is a validated, self-reported instrument for assessing treatment adherence. Participants report how often they engage in each of 5 aspects of non-adherent behavior (forgetting to take a dose, changing the dose, stop taking them for a while, deciding to not take a dose, or taking less than instructed). Scores are summed over the 5 items, the total score ranges from 5 to 25 with higher scores indicating greater self-reported adherence. The MARS was collected at the month 6 and month 12 visits of each treatment period only for those participants receiving oral alendronate during that period.

Outcome measures

Outcome measures
Measure	Alendronate n=115 Participants Participants received alendronate 70 mg orally once a week for 1 year.	Denosumab Participants received denosumab 60 mg subcutaneously every 6 months for 1 year.
Medication Adherence Rating Scale (MARS) to Alendronate in the First Treatment Period Month 6 (n=109)	24.3 scores on a scale Standard Deviation 1.1	—
Medication Adherence Rating Scale (MARS) to Alendronate in the First Treatment Period Month 12 (n= 100)	24.4 scores on a scale Standard Deviation 1.4	—

SECONDARY outcome

Timeframe: Month 18, Month 24 (treatment period 2)

Population: Participants in the PRO analysis set with at least one post-baseline assessment in both periods and with observed data; "n" indicates the number of patients with available data at each time point.

The MARs questionnaire is a validated, self-reported instrument for assessing treatment adherence. Participants report how often they engage in each of 5 aspects of non-adherent behavior (forgetting to take a dose, changing the dose, stop taking them for a while, deciding to not take a dose, or taking less than instructed). Scores are summed over the 5 items, the total score ranges from 5 to 25 with higher scores indicating greater self-reported adherence. The MARS was collected at the month 6 and month 12 visits of each treatment period only for those participants receiving oral alendronate during that period.

Outcome measures

Outcome measures
Measure	Alendronate n=100 Participants Participants received alendronate 70 mg orally once a week for 1 year.	Denosumab Participants received denosumab 60 mg subcutaneously every 6 months for 1 year.
Medication Adherence Rating Scale (MARS) to Alendronate in the Second Treatment Period Treatment period 2 Month 6 (n=98)	23.4 scores on a scale Standard Deviation 2.0	—
Medication Adherence Rating Scale (MARS) to Alendronate in the Second Treatment Period Treatment period 2 Month 12 (n= 90)	23.8 scores on a scale Standard Deviation 1.4	—

Adverse Events

Treatment Period 1: Alendronate

Serious events: 5 serious events

Other events: 24 other events

Deaths: 0 deaths

Treatment Period 1: Denosumab

Serious events: 4 serious events

Other events: 31 other events

Deaths: 0 deaths

Treatment Period 2: Alendronate

Serious events: 4 serious events

Other events: 21 other events

Deaths: 0 deaths

Treatment Period 2: Denosumab

Serious events: 4 serious events

Other events: 13 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Treatment Period 1: Alendronate n=118 participants at risk Participants received alendronate 70 mg orally once a week in year 1.	Treatment Period 1: Denosumab n=125 participants at risk Participants received denosumab 60 mg subcutaneously every 6 months in year 1.	Treatment Period 2: Alendronate n=110 participants at risk Participants who received denosumab 60 mg subcutaneously every 6 months in year 1 then received alendronate 70 mg orally once a week in year 2.	Treatment Period 2: Denosumab n=106 participants at risk Participants who received alendronate 70 mg orally once a week in year 1 then received denosumab 60 mg subcutaneously every 6 months in year 2.
Musculoskeletal and connective tissue disorders Arthralgia	6.8% 8/118 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	8.8% 11/125 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	6.4% 7/110 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.8% 3/106 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Back pain	8.5% 10/118 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.0% 5/125 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.7% 3/110 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	3.8% 4/106 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	4.2% 5/118 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	7.2% 9/125 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	3.6% 4/110 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.7% 5/106 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Nervous system disorders Headache	5.9% 7/118 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	3.2% 4/125 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.7% 3/110 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	2.8% 3/106 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.
Respiratory, thoracic and mediastinal disorders Cough	5.1% 6/118 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.0% 5/125 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	4.5% 5/110 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.	0.94% 1/106 • 24 months In Treatment Period 1, one participant received both treatments and is counted in the denosumab group for safety analyses. The table of Other Adverse Events summarizes the most frequent non-serious occurrences of adverse events.

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 aftercompletion. 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