Osteoporosis
Conditions
Keywords
osteoporosis, low bone mineral density, alendronate, denosumab, adherence, preference, satisfaction, postmenopausal, women
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).
Interventions
DRUGalendronate
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.
DRUGdenosumab
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.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
55 Years to No maximum
Healthy volunteers
No
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: 1. Abnormalities of the esophagus, which delay esophageal emptying such as stricture or achalasia. 2. Inability to stand or sit upright for at least 30 minutes. 3. 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
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;
Participants by arm
| Arm | Count |
|---|---|
| Alendronate in Period 1 Then Denosumab in Period 2 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). | 124 |
| 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). | 126 |
| Total | 250 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Treatment Period 1 | Adverse Event | 5 | 0 |
| Treatment Period 1 | Early crossover | 1 | 3 |
| 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 2 | Adverse Event | 1 | 7 |
| Treatment Period 2 | Complete out of scheduled visit window | 1 | 2 |
| Treatment Period 2 | Non-compliance | 1 | 2 |
| Treatment Period 2 | Protocol-specified criteria | 0 | 1 |
| Treatment Period 2 | Withdrawal by Subject | 0 | 8 |
Baseline characteristics
| Characteristic | Alendronate in Period 1 Then Denosumab in Period 2 | Denosumab in Period 1 Then Alendronate in Period 2 | Total |
|---|---|---|---|
| Age, Continuous | 65.3 Years STANDARD_DEVIATION 7.7 | 65.1 Years STANDARD_DEVIATION 7.6 | 65.2 Years STANDARD_DEVIATION 7.6 |
| Race/Ethnicity, Customized Asian | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 6 Participants | 7 Participants |
| Race/Ethnicity, Customized Japanese | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White or Caucasian | 119 Participants | 115 Participants | 234 Participants |
| Sex: Female, Male Female | 124 Participants | 126 Participants | 250 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 24 / 118 | 31 / 125 | 21 / 110 | 13 / 106 |
| serious Total, serious adverse events | 5 / 118 | 4 / 125 | 4 / 110 | 4 / 106 |
Outcome results
Primary
Adherence With Treatment in the First Treatment Period
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)
Population: The full analysis set (FAS) includes all participants who were randomized.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alendronate | Adherence With Treatment in the First Treatment Period | Yes | 95 Participants |
| Alendronate | Adherence With Treatment in the First Treatment Period | No | 29 Participants |
| Denosumab | Adherence With Treatment in the First Treatment Period | Yes | 111 Participants |
| Denosumab | Adherence With Treatment in the First Treatment Period | No | 15 Participants |
p-value: 0.025995% CI: [1.3, 19.7]Cochran-Mantel-Haenszel
Secondary
Adherence With Treatment in the Second Treatment Period
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)
Population: The cross-over analysis set includes all participants who crossed over to their treatment period 2 treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alendronate | Adherence With Treatment in the Second Treatment Period | Yes | 73 Participants |
| Alendronate | Adherence With Treatment in the Second Treatment Period | No | 42 Participants |
| Denosumab | Adherence With Treatment in the Second Treatment Period | Yes | 98 Participants |
| Denosumab | Adherence With Treatment in the Second Treatment Period | No | 8 Participants |
p-value: <0.000195% CI: [20.6, 41.3]Cochran-Mantel-Haenszel
Secondary
Beliefs About Medicines Questionnaire (BMQ) Concern Score
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
Population: Participants in the PRO analysis set with observed data; n indicates the number of patients with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alendronate | Beliefs About Medicines Questionnaire (BMQ) Concern Score | Month 6 (n=106, 114) | 2.22 scores on a scale | Standard Deviation 0.51 |
| Alendronate | Beliefs About Medicines Questionnaire (BMQ) Concern Score | Month 18 (n=98, 98) | 2.43 scores on a scale | Standard Deviation 0.58 |
| Alendronate | Beliefs About Medicines Questionnaire (BMQ) Concern Score | Month 12 (n=103, 95) | 2.57 scores on a scale | Standard Deviation 0.48 |
| Alendronate | Beliefs About Medicines Questionnaire (BMQ) Concern Score | Month 24 (n=91, 100) | 2.39 scores on a scale | Standard Deviation 0.58 |
| Alendronate | Beliefs About Medicines Questionnaire (BMQ) Concern Score | Baseline (n=104, 117) | 2.33 scores on a scale | Standard Deviation 0.48 |
| Denosumab | Beliefs About Medicines Questionnaire (BMQ) Concern Score | Month 24 (n=91, 100) | 2.18 scores on a scale | Standard Deviation 0.51 |
| Denosumab | Beliefs About Medicines Questionnaire (BMQ) Concern Score | Baseline (n=104, 117) | 2.43 scores on a scale | Standard Deviation 0.46 |
| Denosumab | Beliefs About Medicines Questionnaire (BMQ) Concern Score | Month 6 (n=106, 114) | 2.12 scores on a scale | Standard Deviation 0.51 |
| Denosumab | Beliefs About Medicines Questionnaire (BMQ) Concern Score | Month 12 (n=103, 95) | 2.51 scores on a scale | Standard Deviation 0.5 |
| Denosumab | Beliefs About Medicines Questionnaire (BMQ) Concern Score | Month 18 (n=98, 98) | 2.24 scores on a scale | Standard Deviation 0.49 |
Secondary
Beliefs About Medicines Questionnaire (BMQ): Necessity Score
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
Population: Participants in the PRO analysis set with observed data; n indicates the number of patients with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alendronate | Beliefs About Medicines Questionnaire (BMQ): Necessity Score | Month 6 (n=106, 114) | 3.14 scores on a scale | Standard Deviation 0.53 |
| Alendronate | Beliefs About Medicines Questionnaire (BMQ): Necessity Score | Month 18 (n=98, 98) | 3.20 scores on a scale | Standard Deviation 0.53 |
| Alendronate | Beliefs About Medicines Questionnaire (BMQ): Necessity Score | Month 12 (n=103, 95) | 3.21 scores on a scale | Standard Deviation 0.51 |
| Alendronate | Beliefs About Medicines Questionnaire (BMQ): Necessity Score | Month 24 (n=91, 100) | 3.21 scores on a scale | Standard Deviation 0.62 |
| Alendronate | Beliefs About Medicines Questionnaire (BMQ): Necessity Score | Baseline (n=104, 117) | 3.32 scores on a scale | Standard Deviation 0.52 |
| Denosumab | Beliefs About Medicines Questionnaire (BMQ): Necessity Score | Month 24 (n=91, 100) | 3.22 scores on a scale | Standard Deviation 0.58 |
| Denosumab | Beliefs About Medicines Questionnaire (BMQ): Necessity Score | Baseline (n=104, 117) | 3.26 scores on a scale | Standard Deviation 0.48 |
| Denosumab | Beliefs About Medicines Questionnaire (BMQ): Necessity Score | Month 6 (n=106, 114) | 3.31 scores on a scale | Standard Deviation 0.6 |
| Denosumab | Beliefs About Medicines Questionnaire (BMQ): Necessity Score | Month 12 (n=103, 95) | 3.17 scores on a scale | Standard Deviation 0.52 |
| Denosumab | Beliefs About Medicines Questionnaire (BMQ): Necessity Score | Month 18 (n=98, 98) | 3.28 scores on a scale | Standard Deviation 0.55 |
Secondary
Beliefs About Medicines Questionnaire (BMQ) Preference Score
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
Population: Participants in the PRO analysis set with observed data; n indicates the number of patients with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alendronate | Beliefs About Medicines Questionnaire (BMQ) Preference Score | Month 6 (n=106, 114) | 3.01 scores on a scale | Standard Deviation 0.53 |
| Alendronate | Beliefs About Medicines Questionnaire (BMQ) Preference Score | Month 18 (n=98, 98) | 2.55 scores on a scale | Standard Deviation 0.56 |
| Alendronate | Beliefs About Medicines Questionnaire (BMQ) Preference Score | Month 12 (n=103, 95) | 2.62 scores on a scale | Standard Deviation 0.5 |
| Alendronate | Beliefs About Medicines Questionnaire (BMQ) Preference Score | Month 24 (n=91, 100) | 2.57 scores on a scale | Standard Deviation 0.65 |
| Alendronate | Beliefs About Medicines Questionnaire (BMQ) Preference Score | Baseline (n=104, 117) | 2.97 scores on a scale | Standard Deviation 0.4 |
| Denosumab | Beliefs About Medicines Questionnaire (BMQ) Preference Score | Month 24 (n=91, 100) | 3.80 scores on a scale | Standard Deviation 0.52 |
| Denosumab | Beliefs About Medicines Questionnaire (BMQ) Preference Score | Baseline (n=104, 117) | 3.47 scores on a scale | Standard Deviation 0.43 |
| Denosumab | Beliefs About Medicines Questionnaire (BMQ) Preference Score | Month 6 (n=106, 114) | 3.72 scores on a scale | Standard Deviation 0.47 |
| Denosumab | Beliefs About Medicines Questionnaire (BMQ) Preference Score | Month 12 (n=103, 95) | 3.43 scores on a scale | Standard Deviation 0.45 |
| Denosumab | Beliefs About Medicines Questionnaire (BMQ) Preference Score | Month 18 (n=98, 98) | 3.77 scores on a scale | Standard Deviation 0.47 |
Secondary
Compliance With Treatment in the First Treatment Period
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)
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alendronate | Compliance With Treatment in the First Treatment Period | Yes | 97 Participants |
| Alendronate | Compliance With Treatment in the First Treatment Period | No | 27 Participants |
| Denosumab | Compliance With Treatment in the First Treatment Period | Yes | 114 Participants |
| Denosumab | Compliance With Treatment in the First Treatment Period | No | 12 Participants |
p-value: 0.013895% CI: [2.2, 19.7]Cochran-Mantel-Haenszel
Secondary
Compliance With Treatment in the Second Treatment Period
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)
Population: Crossover set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alendronate | Compliance With Treatment in the Second Treatment Period | Yes | 78 Participants |
| Alendronate | Compliance With Treatment in the Second Treatment Period | No | 37 Participants |
| Denosumab | Compliance With Treatment in the Second Treatment Period | Yes | 99 Participants |
| Denosumab | Compliance With Treatment in the Second Treatment Period | No | 7 Participants |
p-value: <0.000195% CI: [17.6, 37.7]Cochran-Mantel-Haenszel
Secondary
Medication Adherence Rating Scale (MARS) to Alendronate in the First Treatment Period
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)
Population: Participants in the PRO analysis set with observed data; n indicates the number of patients with available data at each time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alendronate | 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 |
| Alendronate | 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
Medication Adherence Rating Scale (MARS) to Alendronate in the Second Treatment Period
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)
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alendronate | 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 |
| Alendronate | 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 |
Secondary
Overall Satisfaction to Study Treatment
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)
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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alendronate | Overall Satisfaction to Study Treatment | A little satisfied | 1 Participants |
| Alendronate | Overall Satisfaction to Study Treatment | Quite satisfied | 34 Participants |
| Alendronate | Overall Satisfaction to Study Treatment | Moderately satisfied | 17 Participants |
| Alendronate | Overall Satisfaction to Study Treatment | Very satisfied | 59 Participants |
| Alendronate | Overall Satisfaction to Study Treatment | Not at all satisfied | 3 Participants |
| Denosumab | Overall Satisfaction to Study Treatment | Very satisfied | 95 Participants |
| Denosumab | Overall Satisfaction to Study Treatment | Not at all satisfied | 3 Participants |
| Denosumab | Overall Satisfaction to Study Treatment | A little satisfied | 3 Participants |
| Denosumab | Overall Satisfaction to Study Treatment | Moderately satisfied | 2 Participants |
| Denosumab | Overall Satisfaction to Study Treatment | Quite satisfied | 18 Participants |
Secondary
Persistence With Treatment in the First Treatment Period
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)
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alendronate | Persistence With Treatment in the First Treatment Period | No | 25 Participants |
| Alendronate | Persistence With Treatment in the First Treatment Period | Yes | 99 Participants |
| Denosumab | Persistence With Treatment in the First Treatment Period | Yes | 114 Participants |
| Denosumab | Persistence With Treatment in the First Treatment Period | No | 12 Participants |
p-value: 0.029195% CI: [1.1, 18.5]Cochran-Mantel-Haenszel
Secondary
Persistence With Treatment in the Second Treatment Period
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)
Population: Crossover set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alendronate | Persistence With Treatment in the Second Treatment Period | Yes | 82 Participants |
| Alendronate | Persistence With Treatment in the Second Treatment Period | No | 33 Participants |
| Denosumab | Persistence With Treatment in the Second Treatment Period | Yes | 103 Participants |
| Denosumab | Persistence With Treatment in the Second Treatment Period | No | 3 Participants |
p-value: <0.000195% CI: [18.1, 36.7]Cochran-Mantel-Haenszel
Secondary
Time to Non-adherence to Alendronate Treatment in the First Treatment Period
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)
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alendronate | Time to Non-adherence to Alendronate Treatment in the First Treatment Period | 43.29 weeks | Standard Error 1.46 |
Secondary
Time to Non-adherence to Alendronate Treatment in the Second Treatment Period
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)
Population: Crossover set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alendronate | Time to Non-adherence to Alendronate Treatment in the Second Treatment Period | 39.45 weeks | Standard Error 1.89 |
Secondary
Time to Non-compliance to Alendronate Treatment in the First Treatment Period
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)
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alendronate | Time to Non-compliance to Alendronate Treatment in the First Treatment Period | 43.75 weeks | Standard Error 1.42 |
Secondary
Time to Non-compliance to Alendronate Treatment in the Second Treatment Period
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)
Population: crossover set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alendronate | Time to Non-compliance to Alendronate Treatment in the Second Treatment Period | 39.97 weeks | Standard Error 1.87 |
Secondary
Time to Non-persistence to Alendronate Treatment in the First Treatment Period
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)
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alendronate | Time to Non-persistence to Alendronate Treatment in the First Treatment Period | 44.59 weeks | Standard Error 1.35 |
Secondary
Time to Non-persistence to Alendronate Treatment in the Second Treatment Period
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)
Population: Crossover set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Alendronate | Time to Non-persistence to Alendronate Treatment in the Second Treatment Period | 42.76 weeks | Standard Error 1.69 |