Denosumab Adherence Preference Satisfaction Study

Study Overview
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Brief Summary
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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).

Official Title
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A Multicenter, Randomized, Cross-Over, Open-label Study to Evaluate the Adherence, Preference, and Satisfaction of Denosumab and Alendronate in Postmenopausal Women With Low Bone Mineral Density

Conditions
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Osteoporosis

Intervention / Treatment
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* Drug: alendronate
* Drug: denosumab


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Treatment Sequence B<br>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<br>* 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.<br>Drug: denosumab<br>* 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.<br>|
| Other: Treatment Sequence A<br>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<br>* 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.<br>Drug: denosumab<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Treatment period 1 (Month 1 to Month 12) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Treatment period 2 (Months 13 to 24) | 
| 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). | Treatment period 1 (Month 1 to Month 12) | 
| 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). | Treatment period 2 (Month 13 to Month 24) | 
| 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. | Treatment period 1 (Month 1 to Month 12) | 
| 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. | Treatment period 2 (Month 13 to Month 24) | 
| 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. | Treatment Period 1 (Month 1 to Month 12) | 
| 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. | Treatment Period 2 (Month 13 to Month 24) | 
| 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. | Treatment period 1 (Month 1 to Month 12) | 
| 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. | Treatment period 2 (Month 13 to Month 24) | 
| 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. | Treatment period 1 (Month 1 to Month 12) | 
| 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. | Treatment period 2 (Month 13 to Month 24) | 
| 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. | End of treatment period 1 (Month 12) | 
| 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. | Baseline, Month 6, Month 12, Month 18 and Month 24 | 
| 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. | Baseline and Month 6, Month 12, Month 18, and Month 24 | 
| 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. | Baseline and Month 6, Month 12, Month 18, and Month 24 | 
| 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. | Month 6, Month 12 (treatment period 1) | 
| 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. | Month 18, Month 24 (treatment period 2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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osteoporosis, low bone mineral density, alendronate, denosumab, adherence, preference, satisfaction, postmenopausal, women