Denosumab Adherence Preference Satisfaction Study
Study Details
Study Description
Brief Summary
The primary objective is to evaluate the adherence of subjects to subcutaneous (SC) 60 mg denosumab every 6 months (Q6M) treatment compared to oral 70 mg alendronate once a week (QW) treatment at the end of treatment period 1 (12 months).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: Treatment Sequence B When a subject meets all eligibility criteria and signs the informed consent, they will be randomized in a 1:1 allocation to one of the two treatment Sequences. Subjects randomized to treatment sequence B will receive 70 mg oral alendronate QW for 1-year (Treatment period 1) followed by denosumab 60 mg Q6M SC for 1 year (Treatment Period 2). |
Drug: alendronate
Subjects will take 70 mg QW of oral alendronate for 1 year. If a subject is randomized to Treatment Sequence A they will receive alendronate for 1 year in Treatment Period 2. If a subject is randomized to Treatment Sequence B they will receive alendronate for 1 year in Treatment Period 1.
Drug: denosumab
Subjects will receive 60 mg of denosumab Q6M SC for 1 year. If a subject is randomized to Treatment Sequence A they will receive denosumab for 1 year in Treatment Period 2. If a subject is randomized to Treatment Sequence B they will receive denosumab for 1 year in Treatment Period 1.
|
| Other: Treatment Sequence A When a subject meets all eligibility criteria and signs the informed consent, they will be randomized in a 1:1 allocation to one of the two treatment sequences. Subjects randomized to treatment sequence A will receive 60 mg denosumab Q6M SC for 1-year (Treatment period 1) followed by oral alendronate 70 mg QW for 1 year (Treatment period 2). |
Drug: alendronate
Subjects will take 70 mg QW of oral alendronate for 1 year. If a subject is randomized to Treatment Sequence A they will receive alendronate for 1 year in Treatment Period 2. If a subject is randomized to Treatment Sequence B they will receive alendronate for 1 year in Treatment Period 1.
Drug: denosumab
Subjects will receive 60 mg of denosumab Q6M SC for 1 year. If a subject is randomized to Treatment Sequence A they will receive denosumab for 1 year in Treatment Period 2. If a subject is randomized to Treatment Sequence B they will receive denosumab for 1 year in Treatment Period 1.
|
Outcome Measures
Primary Outcome Measures
- Adherence With Treatment in the First Treatment Period [Treatment period 1 (Month 1 to Month 12)]
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.
Secondary Outcome Measures
- Adherence With Treatment in the Second Treatment Period [Treatment period 2 (Months 13 to 24)]
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.
- Compliance With Treatment in the First Treatment Period [Treatment period 1 (Month 1 to Month 12)]
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).
- Compliance With Treatment in the Second Treatment Period [Treatment period 2 (Month 13 to Month 24)]
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).
- Persistence With Treatment in the First Treatment Period [Treatment period 1 (Month 1 to Month 12)]
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.
- Persistence With Treatment in the Second Treatment Period [Treatment period 2 (Month 13 to Month 24)]
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.
- Time to Non-adherence to Alendronate Treatment in the First Treatment Period [Treatment Period 1 (Month 1 to Month 12)]
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.
- Time to Non-adherence to Alendronate Treatment in the Second Treatment Period [Treatment Period 2 (Month 13 to Month 24)]
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.
- Time to Non-compliance to Alendronate Treatment in the First Treatment Period [Treatment period 1 (Month 1 to Month 12)]
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.
- Time to Non-compliance to Alendronate Treatment in the Second Treatment Period [Treatment period 2 (Month 13 to Month 24)]
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.
- Time to Non-persistence to Alendronate Treatment in the First Treatment Period [Treatment period 1 (Month 1 to Month 12)]
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.
- Time to Non-persistence to Alendronate Treatment in the Second Treatment Period [Treatment period 2 (Month 13 to Month 24)]
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.
- Overall Satisfaction to Study Treatment [End of treatment period 1 (Month 12)]
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".
- Beliefs About Medicines Questionnaire (BMQ): Necessity Score [Baseline, Month 6, Month 12, Month 18 and Month 24]
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.
- Beliefs About Medicines Questionnaire (BMQ) Concern Score [Baseline and Month 6, Month 12, Month 18, and Month 24]
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.
- Beliefs About Medicines Questionnaire (BMQ) Preference Score [Baseline and Month 6, Month 12, Month 18, and Month 24]
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.
- Medication Adherence Rating Scale (MARS) to Alendronate in the First Treatment Period [Month 6, Month 12 (treatment period 1)]
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.
- Medication Adherence Rating Scale (MARS) to Alendronate in the Second Treatment Period [Month 18, Month 24 (treatment period 2)]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Ambulatory postmenopausal women based on medical history
-
or = 55 years of age at the start of screening
-
Screening bone mineral density (BMD) values (g/cm²), at the lumbar spine OR femoral neck OR total hip that occur within the specified ranges based on the particular scanner that is used. At least 2 lumbar vertebrae must be evaluable by Dual X-ray Absorptiometry (DXA), or at least one hip must be evaluable by DXA
-
Provide written informed consent before any study specific procedure is performed.
Exclusion Criteria:
-
Any disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
-
Hyper- or hypothyroidism; however, stable subjects, in the investigator's opinion, on thyroid hormone replacement therapy are allowed
-
Current hyper- or hypoparathyroidism
-
Current hypo- or hyper calcemia based on the central laboratory reference ranges for albumin-adjusted serum calcium
-
Rheumatoid arthritis, Paget's disease, Cushing's disease, hyperprolactinemia, or cirrhosis of the liver
-
Any metabolic bone disease, e.g. osteomalacia or osteogenesis imperfecta, which may interfere with the interpretation of the findings
-
Any symptomatic vertebral fracture within 3 months prior to screening
-
Previous participation in clinical trials with denosumab
-
Vitamin D deficiency [25(OH) vitamin D level < 20 ng/mL (<49.9 nmol/L)]
-
Contraindicated to alendronate therapy; contraindications for alendronate therapy include:
-
Abnormalities of the esophagus, which delay esophageal emptying such as stricture or achalasia.
-
Inability to stand or sit upright for at least 30 minutes.
-
Hypersensitivity to alendronate (ALN) or other constituents of ALN tablets.
-
Any known prior bisphosphonate use
-
Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trail (s), or subject is receiving other investigational agent(s).
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Freemantle N, Satram-Hoang S, Tang ET, Kaur P, Macarios D, Siddhanti S, Borenstein J, Kendler DL; DAPS Investigators. Final results of the DAPS (Denosumab Adherence Preference Satisfaction) study: a 24-month, randomized, crossover comparison with alendronate in postmenopausal women. Osteoporos Int. 2012 Jan;23(1):317-26. doi: 10.1007/s00198-011-1780-1. Epub 2011 Sep 17.
- Kendler DL, Macarios D, Lillestol MJ, Moffett A, Satram-Hoang S, Huang J, Kaur P, Tang ET, Wagman RB, Horne R. Influence of patient perceptions and preferences for osteoporosis medication on adherence behavior in the Denosumab Adherence Preference Satisfaction study. Menopause. 2014 Jan;21(1):25-32. doi: 10.1097/GME.0b013e31828f5e5d.
- Kendler DL, McClung MR, Freemantle N, Lillestol M, Moffett AH, Borenstein J, Satram-Hoang S, Yang YC, Kaur P, Macarios D, Siddhanti S; DAPS Investigators. Adherence, preference, and satisfaction of postmenopausal women taking denosumab or alendronate. Osteoporos Int. 2011 Jun;22(6):1725-35. doi: 10.1007/s00198-010-1378-z. Epub 2010 Sep 9.
- 20060232
- DAPS
Study Results
Participant Flow
| Recruitment Details | First subject enrolled 03-Oct-07, last subject enrolled 25-Jun-08; First subject crossovered 22-May-08, last subject crossovered 25-Jun-09; |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Alendronate in Period 1 Then Denosumab in Period 2 | Denosumab in Period 1 Then Alendronate in Period 2 |
|---|---|---|
| Arm/Group Description | 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 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). |
| Period Title: Treatment Period 1 | ||
| STARTED | 124 | 126 |
| Received Treatment | 119 | 124 |
| COMPLETED | 106 | 114 |
| NOT COMPLETED | 18 | 12 |
| Period Title: Treatment Period 1 | ||
| STARTED | 106 | 115 |
| Received Treatment | 106 | 110 |
| COMPLETED | 103 | 95 |
| NOT COMPLETED | 3 | 20 |
Baseline Characteristics
| Arm/Group Title | Alendronate in Period 1 Then Denosumab in Period 2 | Denosumab in Period 1 Then Alendronate in Period 2 | Total |
|---|---|---|---|
| Arm/Group Description | 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 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 of all reporting groups |
| Overall Participants | 124 | 126 | 250 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
65.3
(7.7)
|
65.1
(7.6)
|
65.2
(7.6)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
124
100%
|
126
100%
|
250
100%
|
| Male |
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Number) [Number] | |||
| White or Caucasian |
119
96%
|
115
91.3%
|
234
93.6%
|
| Black or African American |
2
1.6%
|
2
1.6%
|
4
1.6%
|
| Hispanic or Latino |
1
0.8%
|
6
4.8%
|
7
2.8%
|
| Asian |
1
0.8%
|
3
2.4%
|
4
1.6%
|
| Japanese |
1
0.8%
|
0
0%
|
1
0.4%
|
Outcome Measures
| Title | Adherence With Treatment in the First Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | Treatment period 1 (Month 1 to Month 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The full analysis set (FAS) includes all participants who were randomized. |
| Arm/Group Title | Alendronate | Denosumab |
|---|---|---|
| Arm/Group Description | Participants received alendronate 70 mg orally once a week for 1 year. | Participants received denosumab 60 mg subcutaneously every 6 months for 1 year. |
| Measure Participants | 124 | 126 |
| Yes |
95
76.6%
|
111
88.1%
|
| No |
29
23.4%
|
15
11.9%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Alendronate, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0259 |
| Comments | All statistical hypothesis tests were conducted at the 0.05 significance level. No adjustment was employed for multiple comparisons. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by center and prior osteoporotic fracture | |
| Method of Estimation | Estimation Parameter | Risk Difference (RD) |
| Estimated Value | 10.5 | |
| Confidence Interval |
(2-Sided) 95% 1.3 to 19.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Positive values for absolute risk reduction favor denosumab. | |
| Title | Adherence With Treatment in the Second Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | Treatment period 2 (Months 13 to 24) |
Outcome Measure Data
| Analysis Population Description |
|---|
| The cross-over analysis set includes all participants who crossed over to their treatment period 2 treatment. |
| Arm/Group Title | Alendronate | Denosumab |
|---|---|---|
| Arm/Group Description | Participants received alendronate 70 mg orally once a week for 1 year. | Participants received denosumab 60 mg subcutaneously every 6 months for 1 year. |
| Measure Participants | 115 | 106 |
| Yes |
73
58.9%
|
98
77.8%
|
| No |
42
33.9%
|
8
6.3%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Alendronate, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | All statistical hypothesis tests were conducted at the 0.05 significance level. No adjustment was employed for multiple comparisons. | |
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by center and prior osteoporotic fracture | |
| Method of Estimation | Estimation Parameter | Risk Difference (RD) |
| Estimated Value | 30.9 | |
| Confidence Interval |
(2-Sided) 95% 20.6 to 41.3 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Positive values for absolute risk reduction favor denosumab. | |
| Title | Compliance With Treatment in the First Treatment Period |
|---|---|
| Description | 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). |
| Time Frame | Treatment period 1 (Month 1 to Month 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Alendronate | Denosumab |
|---|---|---|
| Arm/Group Description | Participants received alendronate 70 mg orally once a week for 1 year. | Participants received denosumab 60 mg subcutaneously every 6 months for 1 year. |
| Measure Participants | 124 | 126 |
| Yes |
97
78.2%
|
114
90.5%
|
| No |
27
21.8%
|
12
9.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Alendronate, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0138 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by center and prior osteoporotic fracture. | |
| Method of Estimation | Estimation Parameter | Risk Difference (RD) |
| Estimated Value | 11.00 | |
| Confidence Interval |
(2-Sided) 95% 2.2 to 19.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Positive values for absolute risk reduction favor denosumab. | |
| Title | Compliance With Treatment in the Second Treatment Period |
|---|---|
| Description | 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). |
| Time Frame | Treatment period 2 (Month 13 to Month 24) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Crossover set |
| Arm/Group Title | Alendronate | Denosumab |
|---|---|---|
| Arm/Group Description | Participants received alendronate 70 mg orally once a week for 1 year. | Participants received denosumab 60 mg subcutaneously every 6 months for 1 year. |
| Measure Participants | 115 | 106 |
| Yes |
78
62.9%
|
99
78.6%
|
| No |
37
29.8%
|
7
5.6%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Alendronate, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by center and prior osteoporotic fracture. | |
| Method of Estimation | Estimation Parameter | Risk Difference (RD) |
| Estimated Value | 27.7 | |
| Confidence Interval |
(2-Sided) 95% 17.6 to 37.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Positive values for absolute risk reduction favor denosumab. | |
| Title | Persistence With Treatment in the First Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | Treatment period 1 (Month 1 to Month 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Alendronate | Denosumab |
|---|---|---|
| Arm/Group Description | Participants received alendronate 70 mg orally once a week for 1 year. | Participants received denosumab 60 mg subcutaneously every 6 months for 1 year. |
| Measure Participants | 124 | 126 |
| Yes |
99
79.8%
|
114
90.5%
|
| No |
25
20.2%
|
12
9.5%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Alendronate, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0291 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by center and prior osteoporotic fracture. | |
| Method of Estimation | Estimation Parameter | Risk Difference (RD) |
| Estimated Value | 9.8 | |
| Confidence Interval |
(2-Sided) 95% 1.1 to 18.5 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Positive values for absolute risk reduction favor denosumab. | |
| Title | Persistence With Treatment in the Second Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | Treatment period 2 (Month 13 to Month 24) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Crossover set |
| Arm/Group Title | Alendronate | Denosumab |
|---|---|---|
| Arm/Group Description | Participants received alendronate 70 mg orally once a week for 1 year. | Participants received denosumab 60 mg subcutaneously every 6 months for 1 year. |
| Measure Participants | 115 | 106 |
| Yes |
82
66.1%
|
103
81.7%
|
| No |
33
26.6%
|
3
2.4%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Alendronate, Denosumab |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other (legacy) | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | ||
| Method | Cochran-Mantel-Haenszel | |
| Comments | Stratified by center and prior osteoporotic fracture. | |
| Method of Estimation | Estimation Parameter | Risk Difference (RD) |
| Estimated Value | 27.4 | |
| Confidence Interval |
(2-Sided) 95% 18.1 to 36.7 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Positive values for absolute risk reduction favor denosumab. | |
| Title | Time to Non-adherence to Alendronate Treatment in the First Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | Treatment Period 1 (Month 1 to Month 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Alendronate |
|---|---|
| Arm/Group Description | Participants received alendronate 70 mg orally once a week for 1 year. |
| Measure Participants | 124 |
| Mean (Standard Error) [weeks] |
43.29
(1.46)
|
| Title | Time to Non-adherence to Alendronate Treatment in the Second Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | Treatment Period 2 (Month 13 to Month 24) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Crossover set |
| Arm/Group Title | Alendronate |
|---|---|
| Arm/Group Description | Participants received alendronate 70 mg orally once a week for 1 year. |
| Measure Participants | 115 |
| Mean (Standard Error) [weeks] |
39.45
(1.89)
|
| Title | Time to Non-compliance to Alendronate Treatment in the First Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | Treatment period 1 (Month 1 to Month 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Alendronate |
|---|---|
| Arm/Group Description | Participants received alendronate 70 mg orally once a week for 1 year. |
| Measure Participants | 124 |
| Mean (Standard Error) [weeks] |
43.75
(1.42)
|
| Title | Time to Non-compliance to Alendronate Treatment in the Second Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | Treatment period 2 (Month 13 to Month 24) |
Outcome Measure Data
| Analysis Population Description |
|---|
| crossover set |
| Arm/Group Title | Alendronate |
|---|---|
| Arm/Group Description | Participants received alendronate 70 mg orally once a week for 1 year. |
| Measure Participants | 115 |
| Mean (Standard Error) [weeks] |
39.97
(1.87)
|
| Title | Time to Non-persistence to Alendronate Treatment in the First Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | Treatment period 1 (Month 1 to Month 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Full analysis set |
| Arm/Group Title | Alendronate |
|---|---|
| Arm/Group Description | Participants received alendronate 70 mg orally once a week for 1 year. |
| Measure Participants | 124 |
| Mean (Standard Error) [weeks] |
44.59
(1.35)
|
| Title | Time to Non-persistence to Alendronate Treatment in the Second Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | Treatment period 2 (Month 13 to Month 24) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Crossover set |
| Arm/Group Title | Alendronate |
|---|---|
| Arm/Group Description | Participants received alendronate 70 mg orally once a week for 1 year. |
| Measure Participants | 115 |
| Mean (Standard Error) [weeks] |
42.76
(1.69)
|
| Title | Overall Satisfaction to Study Treatment |
|---|---|
| Description | 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". |
| Time Frame | End of treatment period 1 (Month 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Alendronate | Denosumab |
|---|---|---|
| Arm/Group Description | Participants received alendronate 70 mg orally once a week for 1 year. | Participants received denosumab 60 mg subcutaneously every 6 months for 1 year. |
| Measure Participants | 114 | 121 |
| Not at all satisfied |
3
2.4%
|
3
2.4%
|
| A little satisfied |
1
0.8%
|
3
2.4%
|
| Moderately satisfied |
17
13.7%
|
2
1.6%
|
| Quite satisfied |
34
27.4%
|
18
14.3%
|
| Very satisfied |
59
47.6%
|
95
75.4%
|
| Title | Beliefs About Medicines Questionnaire (BMQ): Necessity Score |
|---|---|
| Description | 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. |
| Time Frame | Baseline, Month 6, Month 12, Month 18 and Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PRO analysis set with observed data; "n" indicates the number of patients with available data at each time point. |
| Arm/Group Title | Alendronate | Denosumab |
|---|---|---|
| Arm/Group Description | Participants received alendronate 70 mg orally once a week for 1 year. | Participants received denosumab 60 mg subcutaneously every 6 months for 1 year. |
| Measure Participants | 115 | 121 |
| Baseline (n=104, 117) |
3.32
(0.52)
|
3.26
(0.48)
|
| Month 6 (n=106, 114) |
3.14
(0.53)
|
3.31
(0.60)
|
| Month 12 (n=103, 95) |
3.21
(0.51)
|
3.17
(0.52)
|
| Month 18 (n=98, 98) |
3.20
(0.53)
|
3.28
(0.55)
|
| Month 24 (n=91, 100) |
3.21
(0.62)
|
3.22
(0.58)
|
| Title | Beliefs About Medicines Questionnaire (BMQ) Concern Score |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Month 6, Month 12, Month 18, and Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PRO analysis set with observed data; "n" indicates the number of patients with available data at each time point. |
| Arm/Group Title | Alendronate | Denosumab |
|---|---|---|
| Arm/Group Description | Participants received alendronate 70 mg orally once a week for 1 year. | Participants received denosumab 60 mg subcutaneously every 6 months for 1 year. |
| Measure Participants | 115 | 121 |
| Baseline (n=104, 117) |
2.33
(0.48)
|
2.43
(0.46)
|
| Month 6 (n=106, 114) |
2.22
(0.51)
|
2.12
(0.51)
|
| Month 12 (n=103, 95) |
2.57
(0.48)
|
2.51
(0.50)
|
| Month 18 (n=98, 98) |
2.43
(0.58)
|
2.24
(0.49)
|
| Month 24 (n=91, 100) |
2.39
(0.58)
|
2.18
(0.51)
|
| Title | Beliefs About Medicines Questionnaire (BMQ) Preference Score |
|---|---|
| Description | 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. |
| Time Frame | Baseline and Month 6, Month 12, Month 18, and Month 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PRO analysis set with observed data; "n" indicates the number of patients with available data at each time point. |
| Arm/Group Title | Alendronate | Denosumab |
|---|---|---|
| Arm/Group Description | Participants received alendronate 70 mg orally once a week for 1 year. | Participants received denosumab 60 mg subcutaneously every 6 months for 1 year. |
| Measure Participants | 115 | 121 |
| Baseline (n=104, 117) |
2.97
(0.40)
|
3.47
(0.43)
|
| Month 6 (n=106, 114) |
3.01
(0.53)
|
3.72
(0.47)
|
| Month 12 (n=103, 95) |
2.62
(0.50)
|
3.43
(0.45)
|
| Month 18 (n=98, 98) |
2.55
(0.56)
|
3.77
(0.47)
|
| Month 24 (n=91, 100) |
2.57
(0.65)
|
3.80
(0.52)
|
| Title | Medication Adherence Rating Scale (MARS) to Alendronate in the First Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | Month 6, Month 12 (treatment period 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the PRO analysis set with observed data; "n" indicates the number of patients with available data at each time point. |
| Arm/Group Title | Alendronate |
|---|---|
| Arm/Group Description | Participants received alendronate 70 mg orally once a week for 1 year. |
| Measure Participants | 115 |
| Month 6 (n=109) |
24.3
(1.1)
|
| Month 12 (n= 100) |
24.4
(1.4)
|
| Title | Medication Adherence Rating Scale (MARS) to Alendronate in the Second Treatment Period |
|---|---|
| Description | 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. |
| Time Frame | Month 18, Month 24 (treatment period 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Alendronate |
|---|---|
| Arm/Group Description | Participants received alendronate 70 mg orally once a week for 1 year. |
| Measure Participants | 100 |
| Treatment period 2 Month 6 (n=98) |
23.4
(2.0)
|
| Treatment period 2 Month 12 (n= 90) |
23.8
(1.4)
|
Adverse Events
| Time Frame | 24 months | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | 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. | |||||||
| Arm/Group Title | Treatment Period 1: Alendronate | Treatment Period 1: Denosumab | Treatment Period 2: Alendronate | Treatment Period 2: Denosumab | ||||
| Arm/Group Description | Participants received alendronate 70 mg orally once a week in year 1. | Participants received denosumab 60 mg subcutaneously every 6 months in year 1. | 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. | 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. | ||||
All Cause Mortality |
||||||||
| Treatment Period 1: Alendronate | Treatment Period 1: Denosumab | Treatment Period 2: Alendronate | Treatment Period 2: Denosumab | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Treatment Period 1: Alendronate | Treatment Period 1: Denosumab | Treatment Period 2: Alendronate | Treatment Period 2: Denosumab | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/118 (4.2%) | 4/125 (3.2%) | 4/110 (3.6%) | 4/106 (3.8%) | ||||
| Cardiac disorders | ||||||||
| Atrial fibrillation | 1/118 (0.8%) | 0/125 (0%) | 0/110 (0%) | 0/106 (0%) | ||||
| Cardiac failure congestive | 1/118 (0.8%) | 0/125 (0%) | 0/110 (0%) | 0/106 (0%) | ||||
| General disorders | ||||||||
| Chest pain | 0/118 (0%) | 1/125 (0.8%) | 0/110 (0%) | 0/106 (0%) | ||||
| Hernia pain | 0/118 (0%) | 0/125 (0%) | 1/110 (0.9%) | 0/106 (0%) | ||||
| Pain | 1/118 (0.8%) | 0/125 (0%) | 0/110 (0%) | 0/106 (0%) | ||||
| Pelvic mass | 0/118 (0%) | 0/125 (0%) | 0/110 (0%) | 1/106 (0.9%) | ||||
| Infections and infestations | ||||||||
| Clostridium difficile colitis | 1/118 (0.8%) | 0/125 (0%) | 0/110 (0%) | 0/106 (0%) | ||||
| Diverticulitis | 0/118 (0%) | 1/125 (0.8%) | 0/110 (0%) | 0/106 (0%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Pubis fracture | 0/118 (0%) | 0/125 (0%) | 0/110 (0%) | 1/106 (0.9%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Fracture nonunion | 0/118 (0%) | 0/125 (0%) | 1/110 (0.9%) | 0/106 (0%) | ||||
| Joint contracture | 0/118 (0%) | 0/125 (0%) | 1/110 (0.9%) | 0/106 (0%) | ||||
| Lumbar spinal stenosis | 1/118 (0.8%) | 0/125 (0%) | 0/110 (0%) | 0/106 (0%) | ||||
| Muscle spasms | 1/118 (0.8%) | 0/125 (0%) | 0/110 (0%) | 0/106 (0%) | ||||
| Osteoarthritis | 0/118 (0%) | 2/125 (1.6%) | 0/110 (0%) | 1/106 (0.9%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Breast cancer | 0/118 (0%) | 0/125 (0%) | 1/110 (0.9%) | 0/106 (0%) | ||||
| Ovarian neoplasm | 0/118 (0%) | 0/125 (0%) | 0/110 (0%) | 1/106 (0.9%) | ||||
| Squamous cell carcinoma | 1/118 (0.8%) | 0/125 (0%) | 0/110 (0%) | 0/106 (0%) | ||||
| Nervous system disorders | ||||||||
| Cerebrovascular accident | 0/118 (0%) | 0/125 (0%) | 0/110 (0%) | 1/106 (0.9%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Chronic obstructive pulmonary disease | 0/118 (0%) | 0/125 (0%) | 0/110 (0%) | 1/106 (0.9%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Treatment Period 1: Alendronate | Treatment Period 1: Denosumab | Treatment Period 2: Alendronate | Treatment Period 2: Denosumab | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 24/118 (20.3%) | 31/125 (24.8%) | 21/110 (19.1%) | 13/106 (12.3%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthralgia | 8/118 (6.8%) | 11/125 (8.8%) | 7/110 (6.4%) | 3/106 (2.8%) | ||||
| Back pain | 10/118 (8.5%) | 5/125 (4%) | 3/110 (2.7%) | 4/106 (3.8%) | ||||
| Pain in extremity | 5/118 (4.2%) | 9/125 (7.2%) | 4/110 (3.6%) | 5/106 (4.7%) | ||||
| Nervous system disorders | ||||||||
| Headache | 7/118 (5.9%) | 4/125 (3.2%) | 3/110 (2.7%) | 3/106 (2.8%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Cough | 6/118 (5.1%) | 5/125 (4%) | 5/110 (4.5%) | 1/106 (0.9%) | ||||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
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.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Amgen Inc. |
| Phone | 866-572-6436 |
- 20060232
- DAPS