Denosumab Adherence Preference Satisfaction Study
- Registration Number
- NCT00518531
- Lead Sponsor
- Amgen
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 250
- 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.
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Any disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
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Hyper- or hypothyroidism; however, stable subjects, in the investigator's opinion, on thyroid hormone replacement therapy are allowed
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Current hyper- or hypoparathyroidism
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Current hypo- or hyper calcemia based on the central laboratory reference ranges for albumin-adjusted serum calcium
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Rheumatoid arthritis, Paget's disease, Cushing's disease, hyperprolactinemia, or cirrhosis of the liver
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Any metabolic bone disease, e.g. osteomalacia or osteogenesis imperfecta, which may interfere with the interpretation of the findings
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Any symptomatic vertebral fracture within 3 months prior to screening
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Previous participation in clinical trials with denosumab
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Vitamin D deficiency [25(OH) vitamin D level < 20 ng/mL (<49.9 nmol/L)]
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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.
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Any known prior bisphosphonate use
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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).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Treatment Sequence B denosumab 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). Treatment Sequence B alendronate 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). Treatment Sequence A alendronate 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). Treatment Sequence A denosumab 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).
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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).
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-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.
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.
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).
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.
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.
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-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.
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 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.
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.