Post Menopausal Osteoporosis
Conditions
Brief summary
This 2 arm crossover study will evaluate patient reported preference for either once monthly Boniva (150mg p.o.) or once weekly risedronate (35mg p.o.). Patients with post-menopausal osteoporosis will be randomized to receive Boniva for 3 calendar months or risedronate for 12 weeks; they will then cross over to receive the alternative treatment for a further 12 weeks/3 months. The anticipated time on study treatment is 3-12 months, and the target sample size is 100-500 individuals.
Interventions
DRUGRisedronate
35mg po weekly for 12 weeks
150mg po monthly for 3 months
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* ambulatory women with post-menopausal osteoporosis; * patients who are bisphosphonate-naive, or who have previously received oral daily or i.v. bisphosphonate therapy (fulfilling certain criteria detailed in the protocol).
Exclusion criteria
* malignant disease diagnosed within previous 10 years (except for successfully resected basal cell cancer;) breast cancer within previous 20 years; * inability to stand or sit upright for at least 60 minutes; * disease/disorder/treatment with drugs known to influence bone metabolism.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Preferred Ibandronate Monthly Dosing to Risedronate Weekly Dosing | at 6 months | Patients who had taken at least one dose of each study medication were asked to answer a Preference Questionnaire (answered by patients before any study procedures took place at the 6 month visit or at the early termination visit). The questionnaire included three questions on the preferred dosing schedule, and one question asking which schedule was more convenient. No assistance was allowed in completing the questionnaire. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Found Once-monthly Ibandronate to be More Convenient Than Once-weekly Risedronate | within 6 months | Patients who had taken at least one dose of each study medication were asked to answer a Preference Questionnaire (answered by patients before any study procedures took place at the 6 month visit or at the early termination visit). The questionnaire included three questions on the preferred dosing schedule, and one question asking which schedule was more convenient. No assistance was allowed in completing the questionnaire. |
| Intensity of Upper Gastrointestinal (GI) Symptoms | within 3 months | Patients were given a diary in which to record their upper GI events during the first 12 weeks of treatment. The diary was to be completed weekly and the occurrence of symptoms and their intensity recorded using a pre-defined list. |
| Mean Change From Baseline in Bone Resorption and Bone Formation Markers, Serum C-telopeptide of α-chain of Type I Collagen (CTX) and Bone Specific Alkaline Phosphatase (BSAP) | 3 months | During the conduct of this study, it came to the attention of the sponsor that mislabeling of blood samples for the analysis of the bone turnover markers, serum CTX and BSAP, had occurred at more than half of the 44 clinical trial sites. As a result of this mislabeling, the bone turnover marker samples could not be assigned correctly to the two time points at which they were collected (samples collected at baseline and those collected at the crossover visit which occurred after 3 months following the start of trial treatment). Thus, the results of bone turnover markers could not be reliably assessed. Therefore, summary tables showing the mean and median change from baseline for both serum CTX and BSAP for patients randomized to Sequence A (3 months of ibandronate followed by 12 weeks of risedronate) or Sequence B (12 weeks of risedronate followed by 3 months of ibandronate) are not presented, as a valid interpretation of the data cannot be made. |
| Median Change From Baseline in Bone Resorption and Bone Formation Markers, Serum C-telopeptide of α-chain of Type I Collagen (CTX) and Bone Specific Alkaline Phosphatase (BSAP) | 3 months | During the conduct of this study, it came to the attention of the sponsor that mislabeling of blood samples for the analysis of the bone turnover markers, serum CTX and BSAP, had occurred at more than half of the 44 clinical trial sites. As a result of this mislabeling, the bone turnover marker samples could not be assigned correctly to the two time points at which they were collected (samples collected at baseline and those collected at the crossover visit which occurred after 3 months following the start of trial treatment). Thus, the results of bone turnover markers could not be reliably assessed. Therefore, summary tables showing the mean and median change from baseline for both serum CTX and BSAP for patients randomized to Sequence A (3 months of ibandronate followed by 12 weeks of risedronate) or Sequence B (12 weeks of risedronate followed by 3 months of ibandronate) are not presented, as a valid interpretation of the data cannot be made. |
Countries
United States
Participant flow
Recruitment details
Of the 488 patients who were screened, 356 patients were enrolled into the study at 44 centers in the USA and randomized to treatment with ibandronate and risedronate. One hundred eighty patients were randomized to Sequence A (Period 1 ibandronate, Period 2 risedronate), and 176 patients to Sequence B (Period 1 risedronate, Period 2 ibandronate).
Participants by arm
| Arm | Count |
|---|---|
| Sequence A Ibandronate followed by risedronate | 177 |
| Sequence B Risedronate followed by ibandronate | 174 |
| Total | 351 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Administrative | 2 | 1 |
| Overall Study | Adverse Event | 14 | 17 |
| Overall Study | Lost to Follow-up | 4 | 2 |
| Overall Study | Not assigned | 3 | 2 |
| Overall Study | Withdrawal by Subject | 11 | 9 |
Baseline characteristics
| Characteristic | Sequence A | Sequence B | Total |
|---|---|---|---|
| Age, Continuous | 64.6 Years STANDARD_DEVIATION 7 | 64.0 Years STANDARD_DEVIATION 6.7 | 64.3 Years STANDARD_DEVIATION 6.9 |
| Region of Enrollment United States | 177 participants | 174 participants | 351 participants |
| Sex: Female, Male Female | 177 Participants | 174 Participants | 351 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 327 | 0 / 327 |
| serious Total, serious adverse events | 5 / 327 | 3 / 327 |
Outcome results
Primary
Percentage of Participants Who Preferred Ibandronate Monthly Dosing to Risedronate Weekly Dosing
Patients who had taken at least one dose of each study medication were asked to answer a Preference Questionnaire (answered by patients before any study procedures took place at the 6 month visit or at the early termination visit). The questionnaire included three questions on the preferred dosing schedule, and one question asking which schedule was more convenient. No assistance was allowed in completing the questionnaire.
Time frame: at 6 months
Population: Modified Intent to Treat (mITT), defined as the safety analysis set excluding those participants who did not express a preference for one treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| During Sequence A | Percentage of Participants Who Preferred Ibandronate Monthly Dosing to Risedronate Weekly Dosing | 81.7 percentage of participants |
| During Sequence B | Percentage of Participants Who Preferred Ibandronate Monthly Dosing to Risedronate Weekly Dosing | 78.2 percentage of participants |
| Total | Percentage of Participants Who Preferred Ibandronate Monthly Dosing to Risedronate Weekly Dosing | 79.9 percentage of participants |
p-value: <0.0001Garts Test
p-value: <0.0001Prescott Test
Secondary
Intensity of Upper Gastrointestinal (GI) Symptoms
Patients were given a diary in which to record their upper GI events during the first 12 weeks of treatment. The diary was to be completed weekly and the occurrence of symptoms and their intensity recorded using a pre-defined list.
Time frame: within 3 months
Population: Safety analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| During Sequence A | Intensity of Upper Gastrointestinal (GI) Symptoms | Any | 46.1 percentage of participants |
| During Sequence A | Intensity of Upper Gastrointestinal (GI) Symptoms | Mild | 41.3 percentage of participants |
| During Sequence A | Intensity of Upper Gastrointestinal (GI) Symptoms | Moderate | 32.3 percentage of participants |
| During Sequence A | Intensity of Upper Gastrointestinal (GI) Symptoms | Severe | 15.6 percentage of participants |
| During Sequence B | Intensity of Upper Gastrointestinal (GI) Symptoms | Severe | 12.4 percentage of participants |
| During Sequence B | Intensity of Upper Gastrointestinal (GI) Symptoms | Any | 56.5 percentage of participants |
| During Sequence B | Intensity of Upper Gastrointestinal (GI) Symptoms | Moderate | 36.0 percentage of participants |
| During Sequence B | Intensity of Upper Gastrointestinal (GI) Symptoms | Mild | 49.1 percentage of participants |
Secondary
Mean Change From Baseline in Bone Resorption and Bone Formation Markers, Serum C-telopeptide of α-chain of Type I Collagen (CTX) and Bone Specific Alkaline Phosphatase (BSAP)
During the conduct of this study, it came to the attention of the sponsor that mislabeling of blood samples for the analysis of the bone turnover markers, serum CTX and BSAP, had occurred at more than half of the 44 clinical trial sites. As a result of this mislabeling, the bone turnover marker samples could not be assigned correctly to the two time points at which they were collected (samples collected at baseline and those collected at the crossover visit which occurred after 3 months following the start of trial treatment). Thus, the results of bone turnover markers could not be reliably assessed. Therefore, summary tables showing the mean and median change from baseline for both serum CTX and BSAP for patients randomized to Sequence A (3 months of ibandronate followed by 12 weeks of risedronate) or Sequence B (12 weeks of risedronate followed by 3 months of ibandronate) are not presented, as a valid interpretation of the data cannot be made.
Time frame: 3 months
Population: Mislabeling of blood samples for analysis of bone turnover markers resulted in inability to correctly assign samples to two time points at which they were collected (baseline and crossover visit). Results could not be reliably assessed or reported.
Secondary
Median Change From Baseline in Bone Resorption and Bone Formation Markers, Serum C-telopeptide of α-chain of Type I Collagen (CTX) and Bone Specific Alkaline Phosphatase (BSAP)
During the conduct of this study, it came to the attention of the sponsor that mislabeling of blood samples for the analysis of the bone turnover markers, serum CTX and BSAP, had occurred at more than half of the 44 clinical trial sites. As a result of this mislabeling, the bone turnover marker samples could not be assigned correctly to the two time points at which they were collected (samples collected at baseline and those collected at the crossover visit which occurred after 3 months following the start of trial treatment). Thus, the results of bone turnover markers could not be reliably assessed. Therefore, summary tables showing the mean and median change from baseline for both serum CTX and BSAP for patients randomized to Sequence A (3 months of ibandronate followed by 12 weeks of risedronate) or Sequence B (12 weeks of risedronate followed by 3 months of ibandronate) are not presented, as a valid interpretation of the data cannot be made.
Time frame: 3 months
Population: Mislabeling of blood samples for analysis of bone turnover markers resulted in inability to correctly assign samples to two time points at which they were collected (baseline and crossover visit). Results could not be reliably assessed or reported.
Secondary
Percentage of Participants Who Found Once-monthly Ibandronate to be More Convenient Than Once-weekly Risedronate
Patients who had taken at least one dose of each study medication were asked to answer a Preference Questionnaire (answered by patients before any study procedures took place at the 6 month visit or at the early termination visit). The questionnaire included three questions on the preferred dosing schedule, and one question asking which schedule was more convenient. No assistance was allowed in completing the questionnaire.
Time frame: within 6 months
Population: mITT, defined as the safety analysis set excluding those participants who did not express a preference for one treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| During Sequence A | Percentage of Participants Who Found Once-monthly Ibandronate to be More Convenient Than Once-weekly Risedronate | 85.5 percentage of participants |
| During Sequence B | Percentage of Participants Who Found Once-monthly Ibandronate to be More Convenient Than Once-weekly Risedronate | 87.0 percentage of participants |
| Total | Percentage of Participants Who Found Once-monthly Ibandronate to be More Convenient Than Once-weekly Risedronate | 86.3 percentage of participants |