Trial Outcomes & Findings for FOSAMAX PLUS and FOSAMAX PLUS D Re-examination Study (0217A-267) (NCT NCT01065779)

Results Overview

Number of participants that experienced Serious Adverse events (SAE). There was no required routine visit scheduled for AE assessment. AEs were collected through participant self-reporting and assessed by investigators. SAEs were considered serious if the event resulted in: * death or was life-threatening * prolonged an existing inpatient hospitalization * a persistent or significant disability/ incapacity * a congenital anomaly/ birth defect * a significant medical situation, other important medical event based upon appropriate medical judgment of the investigator

Recruitment status

COMPLETED

Target enrollment

880 participants

Primary outcome timeframe

Up to ~ 16 weeks and 14 days after treatment discontinuation

Results posted on

2022-02-03

Participant Flow

Participant milestones

Participant milestones
Measure	FOSAMAX PLUS/ FOSAMAX PLUS D Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly.
Overall Study STARTED	880
Overall Study COMPLETED	798
Overall Study NOT COMPLETED	82

Reasons for withdrawal

Reasons for withdrawal
Measure	FOSAMAX PLUS/ FOSAMAX PLUS D Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly.
Overall Study Duplicate Investigation	1
Overall Study Investigation Before Contract Date	37
Overall Study Non-enrollment Period Administration	10
Overall Study Not Administered With Study Drug	17
Overall Study Failed to Follow-up	10
Overall Study Inclusion Criteria Violation	7

Baseline Characteristics

FOSAMAX PLUS and FOSAMAX PLUS D Re-examination Study (0217A-267)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FOSAMAX PLUS/ FOSAMAX PLUS D n=880 Participants Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly.
Age, Continuous	67.12 years STANDARD_DEVIATION 9.05 • n=5 Participants
Sex/Gender, Customized Female	741 participants n=5 Participants
Sex/Gender, Customized Male	57 participants n=5 Participants
Sex/Gender, Customized Excluded from Analysis	82 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to ~ 16 weeks and 14 days after treatment discontinuation

Population: Safety evaluation was performed in participants who took at least one dose of study medication and completed \> 1 follow up visit.

Number of participants that experienced Serious Adverse events (SAE). There was no required routine visit scheduled for AE assessment. AEs were collected through participant self-reporting and assessed by investigators. SAEs were considered serious if the event resulted in: * death or was life-threatening * prolonged an existing inpatient hospitalization * a persistent or significant disability/ incapacity * a congenital anomaly/ birth defect * a significant medical situation, other important medical event based upon appropriate medical judgment of the investigator

Outcome measures

Outcome measures
Measure	FOSAMAX PLUS/ FOSAMAX PLUS D n=798 Participants Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly.
Number of Participants With Serious Adverse Events	0 Participants

PRIMARY outcome

Timeframe: Up to ~ 16 weeks and 14 days after treatment discontinuation

Population: Safety evaluation was performed in participants who took at least one dose of study medication and completed \> 1 follow up visit.

Number of participants that experienced unexpected Adverse Events (AEs) regardless of whether or not the AE was considered related to the use of the product. There was no required routine visit scheduled for AE assessment. An AE was defined as any unfavorable \& unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product. Any worsening (any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also considered an AE.

Outcome measures

Outcome measures
Measure	FOSAMAX PLUS/ FOSAMAX PLUS D n=798 Participants Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly.
Number of Participants With Unexpected Adverse Events	2 Participants

PRIMARY outcome

Timeframe: Up to ~ 16 weeks and 14 days after treatment discontinuation

Population: Safety evaluation was performed in participants who took at least one dose of study medication and completed \> 1 follow up visit.

An AE was defined as any unfavorable \& unintended change in the structure, function, or chemistry of the body temporally associated with the use of the product, whether or not considered related to the use of the product. Any worsening (any clinically significant adverse change in frequency and/or intensity) of a preexisting condition which is temporally associated with the use of the product, was also considered an AE. There was no required routine visit scheduled for AE assessment. AEs were collected through participant self-reporting and assessed by investigators.

Outcome measures

Outcome measures
Measure	FOSAMAX PLUS/ FOSAMAX PLUS D n=798 Participants Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly.
Number of Participants With Non-Serious AEs	42 Participants

PRIMARY outcome

Timeframe: Baseline and end of Treatment (Up to ~ 16 weeks)

Population: Among 798 participants in safety evaluation, there was a total of 789 participants for efficacy evaluation excluding 8 participants who took study drug for \< 4 weeks and 1 participant who did not enter efficacy evaluation.

Evaluation of disease improvement was conducted in 3 categories of "improved", "unchanged", or "worsened". Changes in biochemical markers and vitamin D levels were reviewed before (baseline) and after treatment using statistical analyses to determine disease status, which was reported as either "improved", "unchanged", or "worsened".

Outcome measures

Outcome measures
Measure	FOSAMAX PLUS/ FOSAMAX PLUS D n=789 Participants Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly.
Number of Participants With Improved, Unchanged, or Worsened Disease Improved	549 Participants
Number of Participants With Improved, Unchanged, or Worsened Disease Unchanged	239 Participants
Number of Participants With Improved, Unchanged, or Worsened Disease Worsened	1 Participants

PRIMARY outcome

Timeframe: Baseline and End of Treatment (Up to ~ 16 weeks)

Population: Among 798 participants in safety evaluation, there was a total of 789 participants for efficacy evaluation excluding 8 participants who took study drug for \< 4 weeks and 1 participant who did not enter efficacy evaluation. Only participants with lab values submitted to Sponsor were included.

For efficacy evaluation, changes in Serum 25-hydroxyvitamin D were evaluated before study drug administration and at end of study drug treatment. Change was calculated as the later time point (at \~16 weeks) minus the earlier time point (baseline). The Last Observation Carried Forward (LOCF) method was used. That is, the last observed non-missing value was used to fill in missing values at the later point in the study.

Outcome measures

Outcome measures
Measure	FOSAMAX PLUS/ FOSAMAX PLUS D n=10 Participants Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly.
Change From Baseline in Serum 25-hydroxyvitamin D at End of Treatment	1.73 ng/mL Standard Deviation 1.48

PRIMARY outcome

Timeframe: Baseline and End of Treatment (Up to ~ 16 weeks)

Population: Among 798 participants in safety evaluation, there was a total of 789 participants for efficacy evaluation excluding 8 participants who took study drug for \< 4 weeks and 1 participant who did not enter efficacy evaluation. Only participants with lab values submitted to Sponsor were included.

For efficacy evaluation, changes in Serum Osteocalcin were evaluated before study drug administration and at end of study drug treatment. Change was calculated as the later time point (at \~16 weeks) minus the earlier time point (baseline). The Last Observation Carried Forward (LOCF) method was used. That is, the last observed non-missing value was used to fill in missing values at the later point in the study.

Outcome measures

Outcome measures
Measure	FOSAMAX PLUS/ FOSAMAX PLUS D n=10 Participants Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly.
Change From Baseline in Serum Osteocalcin at End of Treatment	0.69 ng/mL Standard Deviation 0.32

PRIMARY outcome

Timeframe: Baseline and End of Treatment (Up to ~ 16 weeks)

Population: Among 798 participants in safety evaluation, there was a total of 789 participants for efficacy evaluation excluding 8 participants who took study drug for \< 4 weeks and 1 participant who did not enter efficacy evaluation. Only participants with lab values submitted to Sponsor were included.

For efficacy evaluation, changes in Serum Deoxypyridinoline were evaluated before study drug administration and at end of study drug treatment. Change was calculated as the later time point (at \~16 weeks) minus the earlier time point (baseline). The Last Observation Carried Forward (LOCF) method was used. That is, the last observed non-missing value was used to fill in missing values at the later point in the study.

Outcome measures

Outcome measures
Measure	FOSAMAX PLUS/ FOSAMAX PLUS D n=11 Participants Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly.
Change From Baseline in Urine Deoxypyridinoline at End of Treatment	1.03 nmol/mmol Standard Deviation 0.83

PRIMARY outcome

Timeframe: Baseline and End of Treatment (Up to ~ 16 weeks)

Population: Among 798 participants in safety evaluation, there was a total of 789 participants for efficacy evaluation excluding 8 participants who took study drug for \< 4 weeks and 1 participant who did not enter efficacy evaluation. Only participants with lab values submitted to Sponsor were included.

For efficacy evaluation, changes in Serum Alkaline Phosphatase were evaluated before study drug administration and at end of study drug treatment. Change was calculated as the later time point (at \~16 weeks) minus the earlier time point (baseline). The Last Observation Carried Forward (LOCF) method was used. That is, the last observed non-missing value was used to fill in missing values at the later point in the study.

Outcome measures

Outcome measures
Measure	FOSAMAX PLUS/ FOSAMAX PLUS D n=33 Participants Participants with Osteoporosis treated with FOSAMAX PLUS or FOSAMAX PLUS D. One 70 mg alendronate/2800 International Units (IU) Vitamin D tablet or one 70 mg alendronate/5600 IU Vitamin D tablet taken once weekly.
Change From Baseline in Alkaline Phosphatase at End of Treatment	-16.36 mg/dL Standard Deviation 37.58

Adverse Events

FOSAMAX PLUS/ FOSAMAX PLUS D

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place