Trial Outcomes & Findings for A Study Comparing Monthly Boniva (Ibandronate) and Weekly Risedronate in Women With Post-Menopausal Osteoporosis. (NCT NCT00377234)

NCT ID: NCT00377234

Last Updated: 2016-08-01

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

356 participants

Primary outcome timeframe

at 6 months

Results posted on

2016-08-01

Participant Flow

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).

Participant milestones

Participant milestones
Measure
Sequence A
Ibandronate followed by risedronate
Sequence B
Risedronate followed by ibandronate
Overall Study
STARTED
180
176
Overall Study
Randomized
180
176
Overall Study
Did Not Receive Study Treatment
3
2
Overall Study
Received Treatment
177
174
Overall Study
Safety Analysis Set: Period 1
177
174
Overall Study
Safety Analysis Set: Period 2
153
150
Overall Study
Safety Analysis Set: Ibandronate
177
150
Overall Study
Safety Analysis Set: Risedronate
153
174
Overall Study
COMPLETED
146
145
Overall Study
NOT COMPLETED
34
31

Reasons for withdrawal

Reasons for withdrawal
Measure
Sequence A
Ibandronate followed by risedronate
Sequence B
Risedronate followed by ibandronate
Overall Study
Adverse Event
14
17
Overall Study
Withdrawal by Subject
11
9
Overall Study
Lost to Follow-up
4
2
Overall Study
Administrative
2
1
Overall Study
Not assigned
3
2

Baseline Characteristics

A Study Comparing Monthly Boniva (Ibandronate) and Weekly Risedronate in Women With Post-Menopausal Osteoporosis.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Sequence A
n=177 Participants
Ibandronate followed by risedronate
Sequence B
n=174 Participants
Risedronate followed by ibandronate
Total
n=351 Participants
Total of all reporting groups
Age, Continuous
64.6 Years
STANDARD_DEVIATION 7.0 • n=5 Participants
64.0 Years
STANDARD_DEVIATION 6.7 • n=7 Participants
64.3 Years
STANDARD_DEVIATION 6.9 • n=5 Participants
Sex: Female, Male
Female
177 Participants
n=5 Participants
174 Participants
n=7 Participants
351 Participants
n=5 Participants
Sex: Female, Male
Male
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
Region of Enrollment
United States
177 participants
n=5 Participants
174 participants
n=7 Participants
351 participants
n=5 Participants

PRIMARY outcome

Timeframe: 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

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.

Outcome measures

Outcome measures
Measure
During Sequence A
n=131 Participants
Ibandronate followed by risedronate
During Sequence B
n=147 Participants
Risendronate followed by ibandronate
Total
n=278 Participants
During period 1 + during period 2
Percentage of Participants Who Preferred Ibandronate Monthly Dosing to Risedronate Weekly Dosing
81.7 percentage of participants
78.2 percentage of participants
79.9 percentage of participants

SECONDARY outcome

Timeframe: within 6 months

Population: mITT, defined as the safety analysis set excluding those participants who did not express a preference for one treatment

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.

Outcome measures

Outcome measures
Measure
During Sequence A
n=131 Participants
Ibandronate followed by risedronate
During Sequence B
n=131 Participants
Risendronate followed by ibandronate
Total
n=262 Participants
During period 1 + during period 2
Percentage of Participants Who Found Once-monthly Ibandronate to be More Convenient Than Once-weekly Risedronate
85.5 percentage of participants
87.0 percentage of participants
86.3 percentage of participants

SECONDARY outcome

Timeframe: within 3 months

Population: Safety analysis set

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.

Outcome measures

Outcome measures
Measure
During Sequence A
n=177 Participants
Ibandronate followed by risedronate
During Sequence B
n=174 Participants
Risendronate followed by ibandronate
Total
During period 1 + during period 2
Intensity of Upper Gastrointestinal (GI) Symptoms
Severe
15.6 percentage of participants
12.4 percentage of participants
Intensity of Upper Gastrointestinal (GI) Symptoms
Any
46.1 percentage of participants
56.5 percentage of participants
Intensity of Upper Gastrointestinal (GI) Symptoms
Mild
41.3 percentage of participants
49.1 percentage of participants
Intensity of Upper Gastrointestinal (GI) Symptoms
Moderate
32.3 percentage of participants
36.0 percentage of participants

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome data not reported

Adverse Events

Ibandronate

Serious events: 5 serious events
Other events: 0 other events
Deaths: 0 deaths

Risedronate

Serious events: 3 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Ibandronate
n=327 participants at risk
Ibandronate adverse events
Risedronate
n=327 participants at risk
Risendronate adverse events
Cardiac disorders
Coronary Artery Disease
0.31%
1/327 • Number of events 1 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.
0.00%
0/327 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.
Cardiac disorders
Pericarditis
0.31%
1/327 • Number of events 1 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.
0.00%
0/327 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.
Eye disorders
Vitreous Haemorrhage
0.00%
0/327 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.
0.31%
1/327 • Number of events 1 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.
Gastrointestinal disorders
Abdominal Hernia
0.31%
1/327 • Number of events 1 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.
0.00%
0/327 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.
Gastrointestinal disorders
Small Intestinal Obstruction
0.31%
1/327 • Number of events 1 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.
0.00%
0/327 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.
Gastrointestinal disorders
Umbilical Hernia
0.31%
1/327 • Number of events 1 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.
0.00%
0/327 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.
Injury, poisoning and procedural complications
Post Procedural Haemorrhage
0.31%
1/327 • Number of events 1 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.
0.00%
0/327 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.
Reproductive system and breast disorders
Ovarian Cyst
0.31%
1/327 • Number of events 1 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.
0.00%
0/327 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.
Infections and infestations
Bronchitis
0.00%
0/327 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.
0.31%
1/327 • Number of events 1 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.
Vascular disorders
Malignant Hypertension
0.00%
0/327 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.
0.31%
1/327 • Number of events 1 • Study duration was approximately 6 months (3 months and 12 weeks) and a follow-up period of 15 days after the completion of treatment was included to assess safety information. Participants were assessed for adverse events for a total of 6.5 months.
The safety analysis set is a modified intent to treat population, defined as all subjects who received the respective treatment.

Other adverse events

Adverse event data not reported

Additional Information

Medical Communications

Hoffmann-LaRoche

Phone: 800-821-8590

Results disclosure agreements

  • Principal investigator is a sponsor employee The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.
  • Publication restrictions are in place

Restriction type: OTHER