Osteoporosis, Postmenopausal
Conditions
Keywords
risedronate, Ibandronate, preference, Osteoporosis
Brief summary
This is a randomized open label, multi-centre study for Korean women with postmenopausal osteoporosis, evaluating the preference for either the once-monthly dosing of ibandronate or the once-weekly dosing of risedronate. Eligible subjects will be randomised either ibandronate monthly regimen or risedronate weekly regimen. Treatment period consists of 3 month with ibandronate 150mg and additional 12 week with risedronate 35 mg or vice versa. After taking the first interventional medicine for 3 months or 12 weeks completely, a subject changes the treatment arm. There is no washout period.
Interventions
DRUGIbandronate (SB743830HD)
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Healthy volunteers
No
Inclusion criteria
* Women with postmenopausal osteoporosis diagnosed by DXA scanning, defined by T-score of -2.5 SD at spine or femur. * Patients who have never received bisphosphonates therapy (bisphosphonates naive)
Exclusion criteria
* Inability to stand or sit in the upright position for at least 60 minutes; * Hypersensitivity to any component of risedronate and ibandronate; * Administration of any investigational drug within 30 days preceding the first dose of the study drug; * Patient has been on hormone (estrogen) replacement therapy or other osteoporosis medication (e.g. SERMS and calcitonin) within the previous 3 months. * Patient has been on systemic corticosteroids therapy for more than 1 month within the past year. * Other bone disease except osteoporosis * Current medical history of uncontrolled major upper GI disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Prefer the Once-monthly Dosing of Ibandronate to the Once-weekly Dosing of Risedronate | Visit 4 (Week 24) | Preference of monthly ibandronate and weekly risedronate was compared. Modified-intention-to-treat (mITT) population was used for analysis. Any participant randomly assigned, received the study drug, and participants were asked to fill the preference questionnaire on completion of study. Preference was calculated as percentage. Data for percentage of participants with preference to once-monthly dosing of ibandronate to the once-weekly dosing of risedronate was presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Choosing Ibandronate or Risedronate as Their Preferred Treatment Based on Convenience of Administration | Visit 4 (Week 24) | Participant's preference for convenient treatment was compared between monthly ibandronate and weekly risedronate. Analysis population was mITT. Preference for convenient treatment was calculated as percentage. Percentage of participants who think once-monthly ibandronate dosing is more convenient over once-weekly risedronate dosing were presented. Those participants who answered the two treatments equally convenient were excluded while reporting. |
| Mean Percent Change of Serum C-terminal Telopeptide (CTx) From Baseline to Visit 3 for Once-monthly Dosing of Ibandronate & Once-weekly Dosing of Risedronate | Baseline (Week 0) and Visit 3 (Week 12) | The difference of change in serum CTX from basal value between the two sequences was tested using ANCOVA at 95% confidence interval at 3 months (Visit 3) after the administration. Analysis was done with PP population. Baseline was value at Week 0, Change from baseline was calculated by subtracting Baseline value from value at specified time point. |
Participant flow
Recruitment details
A total of 365 korean female participants with postmenopausal osteoporosis were enrolled in this study, conducted for 6 months at 15 centers in South Korea.
Pre-assignment details
A total of 365 participants were randomized in the study. Out of the randomized participants 13 were dropped out before administration of drug, remaining 352 participants were included in safety population, 314 participants were included in modified intent to treat population and 308 participants were included in the per-protocol population.
Participants by arm
| Arm | Count |
|---|---|
| Sequence A: Ibandronate 150 mg Then Risedronate 35 mg Participants received treatment of ibandronate 150 mg tablet orally once monthly for 3 months in period 1 and then administered risedronate 35 mg tablet orally once weekly for 12 weeks in period 2 in sequence A. Participants were recommended to take the tablet on the same day every month in case of the once-monthly drug (e.g. on the 15th each month) and on the same day every week in case of the once-weekly drug (e.g. every Sunday). The two drugs were administered on an empty stomach in the morning, followed by an overnight fast (at least 6-hour fast). | 176 |
| Sequence B: Risedronate 35 mg Then Ibandronate 150 mg Participants received treatments of risedronate 35 mg tablet orally once weekly for 12 weeks in period 1 and then administered ibandronate 150 mg tablet orally once monthly for 3 months in period 2 in sequence B. Participants were recommended to take the tablet on the same day every month in case of the once-monthly drug (e.g. on the 15th each month) and on the same day every week in case of the once-weekly drug (e.g. every Sunday). The two drugs were administered on an empty stomach in the morning, followed by an overnight fast (at least 6-hour fast). | 176 |
| Total | 352 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 15 | 14 |
| Overall Study | Data missing | 2 | 0 |
| Overall Study | Did not meet Eligibility criteria | 7 | 2 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Non-compliance | 0 | 1 |
| Overall Study | Other | 1 | 5 |
| Overall Study | Withdrawal by Subject | 4 | 3 |
Baseline characteristics
| Characteristic | Sequence A: Ibandronate 150 mg Then Risedronate 35 mg | Sequence B: Risedronate 35 mg Then Ibandronate 150 mg | Total |
|---|---|---|---|
| Age, Continuous | 61.33 Years STANDARD_DEVIATION 6.53 | 61.99 Years STANDARD_DEVIATION 7.07 | 61.66 Years STANDARD_DEVIATION 6.81 |
| Region of Enrollment South Korea | 176 Participants | 176 Participants | 352 Participants |
| Sex: Female, Male Female | 176 Participants | 176 Participants | 352 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 | 0 / 336 | 0 / 334 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 6 / 336 | 4 / 334 |
Outcome results
Primary
Percentage of Participants Who Prefer the Once-monthly Dosing of Ibandronate to the Once-weekly Dosing of Risedronate
Preference of monthly ibandronate and weekly risedronate was compared. Modified-intention-to-treat (mITT) population was used for analysis. Any participant randomly assigned, received the study drug, and participants were asked to fill the preference questionnaire on completion of study. Preference was calculated as percentage. Data for percentage of participants with preference to once-monthly dosing of ibandronate to the once-weekly dosing of risedronate was presented.
Time frame: Visit 4 (Week 24)
Population: mITT population was comprised of any participant, who was randomly assigned, received the study drug once more at each phase, filled out the preference questionnaire at the completion of the study. Percentages do not sum to 100 because some participants did not express a preference.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ibandronate 150 mg Once Monthly | Percentage of Participants Who Prefer the Once-monthly Dosing of Ibandronate to the Once-weekly Dosing of Risedronate | 62.42 Percentage of participants |
| Risedronate 35 mg Once Weekly | Percentage of Participants Who Prefer the Once-monthly Dosing of Ibandronate to the Once-weekly Dosing of Risedronate | 21.02 Percentage of participants |
p-value: <0.0001Chi-squared
Secondary
Mean Percent Change of Serum C-terminal Telopeptide (CTx) From Baseline to Visit 3 for Once-monthly Dosing of Ibandronate & Once-weekly Dosing of Risedronate
The difference of change in serum CTX from basal value between the two sequences was tested using ANCOVA at 95% confidence interval at 3 months (Visit 3) after the administration. Analysis was done with PP population. Baseline was value at Week 0, Change from baseline was calculated by subtracting Baseline value from value at specified time point.
Time frame: Baseline (Week 0) and Visit 3 (Week 12)
Population: Per protocol population comprised of any participant, who didn't violate the study protocol, filled the preference questionnaire at the completion of the study, finished assessment of bone turnover marker, and completed journal of GI symptoms. Only the participants available at the time of assessment were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ibandronate 150 mg Once Monthly | Mean Percent Change of Serum C-terminal Telopeptide (CTx) From Baseline to Visit 3 for Once-monthly Dosing of Ibandronate & Once-weekly Dosing of Risedronate | -57.23 Percent change | Standard Deviation 35.89 |
| Risedronate 35 mg Once Weekly | Mean Percent Change of Serum C-terminal Telopeptide (CTx) From Baseline to Visit 3 for Once-monthly Dosing of Ibandronate & Once-weekly Dosing of Risedronate | -56.95 Percent change | Standard Deviation 37.07 |
p-value: 0.9456t-test, 2 sided
Secondary
Percentage of Participants Choosing Ibandronate or Risedronate as Their Preferred Treatment Based on Convenience of Administration
Participant's preference for convenient treatment was compared between monthly ibandronate and weekly risedronate. Analysis population was mITT. Preference for convenient treatment was calculated as percentage. Percentage of participants who think once-monthly ibandronate dosing is more convenient over once-weekly risedronate dosing were presented. Those participants who answered the two treatments equally convenient were excluded while reporting.
Time frame: Visit 4 (Week 24)
Population: mITT Population. Percentages do not sum to 100 because some participants did not express a preference.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ibandronate 150 mg Once Monthly | Percentage of Participants Choosing Ibandronate or Risedronate as Their Preferred Treatment Based on Convenience of Administration | 72.93 Percentage of particiants |
| Risedronate 35 mg Once Weekly | Percentage of Participants Choosing Ibandronate or Risedronate as Their Preferred Treatment Based on Convenience of Administration | 13.69 Percentage of particiants |
p-value: <0.0001Chi-squared