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A Study to Evaluate Alendronate Sodium /Vitamin D3 Combination Tablets(FOSAMAX PLUS) Versus Calcitriol in the Treatment of Osteoporosis in Postmenopausal Women in China (MK-0217A-264)

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ClinicalTrials.gov Identifier: NCT01350934
Recruitment Status : Completed
First Posted : May 10, 2011
Results First Posted : July 22, 2014
Last Update Posted : August 24, 2018
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Osteoporosis, Postmenopausal
Interventions Drug: alendronate 70-mg/vitamin D3 5600 IU combination tablet (Fosamax Plus)
Drug: Calcitriol
Dietary Supplement: Calcium 500 mg
Enrollment 219
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Fosamax Plus Calcitriol
Hide Arm/Group Description Participants received alendronate 70 mg plus vitamin D3 5600 IU in a combination tablet (FOSAMAX PLUS D) once weekly for 6 months (base study), and then once weekly for another 6 months (extension study). Participants received calcitriol 0.25 μg once daily orally for 6 months (base study), and then once daily orally for another 6 months (extension study).
Period Title: Base Study
Started 111 108
Completed 100 105
Not Completed 11 3
Reason Not Completed
Adverse Event             6             0
Lost to Follow-up             1             0
Protocol Violation             1             1
Withdrawal by Subject             1             2
Non-Compliance With Study Drug             2             0
Period Title: Extension Study
Started 100 105
Completed 95 101
Not Completed 5 4
Reason Not Completed
Adverse Event             2             1
Lost to Follow-up             2             0
Protocol Violation             1             1
Lack of Efficacy             0             1
Withdrawal by Subject             0             1
Arm/Group Title Fosamax Plus Calcitriol Total
Hide Arm/Group Description Participants received alendronate 70 mg plus vitamin D3 5600 IU in a combination tablet (FOSAMAX PLUS D) once weekly for 6 months (base study), and then once weekly for another 6 months (extension study). Participants received calcitriol 0.25 μg once daily orally for 6 months (base study), and then once daily orally for another 6 months (extension study). Total of all reporting groups
Overall Number of Baseline Participants 101 107 208
Hide Baseline Analysis Population Description
Full Analysis Set (FAS) population, which consisted of all randomized participants who received at least one dose of study treatment, had at least one post-randomization observation for the analysis endpoint subsequent to at least one dose of study treatment, and had baseline data for analyses that required baseline data.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 101 participants 107 participants 208 participants
65.6  (7.97) 64.8  (7.44) 65.2  (7.69)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 101 participants 107 participants 208 participants
Female
101
 100.0%
107
 100.0%
208
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Base Study: Percentage Change From Baseline in Lumbar Spine Bone Mineral Density (BMD) at Month 6
Hide Description BMD at the lumbar spine was assessed by dual energy X-ray absorptiometry (DXA) at baseline and Month 6.
Time Frame Baseline and Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) population, which consisted of all randomized participants who received at least one dose of study treatment, had at least one post-randomization observation for the analysis endpoint subsequent to at least one dose of study treatment, and had baseline data for analyses that required baseline data.
Arm/Group Title Fosamax Plus Calcitriol
Hide Arm/Group Description:
Participants received alendronate 70 mg plus vitamin D3 5600 IU in a combination tablet (FOSAMAX PLUS D) once weekly for 6 months (base study), and then once weekly for another 6 months (extension study).
Participants received calcitriol 0.25 μg once daily orally for 6 months (base study), and then once daily orally for another 6 months (extension study).
Overall Number of Participants Analyzed 101 107
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent change
3.54
(2.7 to 4.4)
1.59
(0.8 to 2.4)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fosamax Plus, Calcitriol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Longitudinal data analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference
Estimated Value 1.95
Confidence Interval (2-Sided) 95%
0.8 to 3.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.56
Estimation Comments [Not Specified]
2.Primary Outcome
Title Extension Study: Percentage Change From Baseline in Lumbar Spine BMD at Month 12
Hide Description BMD at the lumbar spine was assessed by DXA at baseline and Month 12.
Time Frame Baseline and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) population, which consisted of all randomized participants who received at least one dose of study treatment, had at least one post-randomization observation for the analysis endpoint subsequent to at least one dose of study treatment, and had baseline data for analyses that required baseline data.
Arm/Group Title Fosamax Plus Calcitriol
Hide Arm/Group Description:
Participants received alendronate 70 mg plus vitamin D3 5600 IU in a combination tablet (FOSAMAX PLUS D) once weekly for 6 months (base study), and then once weekly for another 6 months (extension study).
Participants received calcitriol 0.25 μg once daily orally for 6 months (base study), and then once daily orally for another 6 months (extension study).
Overall Number of Participants Analyzed 97 104
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent change
5.17
(4.3 to 6.0)
2.26
(1.4 to 3.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fosamax Plus, Calcitriol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Longitudinal data analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Estimated Difference
Estimated Value 2.92
Confidence Interval (2-Sided) 95%
1.8 to 4.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.59
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Base Study: Percentage Change From Baseline in Serum Procollagen Type 1 N-Terminal Propeptide (s-P1NP) at Month 6
Hide Description s-P1NP is a biochemical marker of bone turnover that is particularly useful in monitoring bone resorption, a process by which bone is broken down within the body. s-P1NP was measured at baseline and Month 6.
Time Frame Baseline and Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Per-Protocol Set (PPS) population, which consisted of participants who received one dose of study treatment, had baseline measurement and had a Month 6 observation for the analysis endpoint, but excluded participants with at least one major protocol deviation.
Arm/Group Title Fosamax Plus Calcitriol
Hide Arm/Group Description:
Participants received alendronate 70 mg plus vitamin D3 5600 IU in a combination tablet (FOSAMAX PLUS D) once weekly for 6 months (base study), and then once weekly for another 6 months (extension study).
Participants received calcitriol 0.25 μg once daily orally for 6 months (base study), and then once daily orally for another 6 months (extension study).
Overall Number of Participants Analyzed 98 105
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent change
-59.12
(-62.03 to -55.98)
-16.75
(-22.53 to -10.54)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fosamax Plus, Calcitriol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Constrained longitudinal data analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -42.37
Confidence Interval (2-Sided) 95%
-48.16 to -36.67
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Base Study: Percentage Change From Baseline in Serum C-Telopeptides of Type 1 Collagen (s-CTx) at Month 6
Hide Description s-CTx is a biochemical marker for bone turnover that has been shown to detect increased bone resorption, a process by which bone is broken down within the body. s-CTx was measured at baseline and Month 6.
Time Frame Baseline and Month 6
Hide Outcome Measure Data
Hide Analysis Population Description
Per-Protocol Set (PPS) population, which consisted of participants who received one dose of study treatment, had baseline measurement and had a Month 6 observation for the analysis endpoint, but excluded participants with at least one major protocol deviation.
Arm/Group Title Fosamax Plus Calcitriol
Hide Arm/Group Description:
Participants received alendronate 70 mg plus vitamin D3 5600 IU in a combination tablet (FOSAMAX PLUS D) once weekly for 6 months (base study), and then once weekly for another 6 months (extension study).
Participants received calcitriol 0.25 μg once daily orally for 6 months (base study), and then once daily orally for another 6 months (extension study).
Overall Number of Participants Analyzed 98 105
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent change
-79.23
(-81.40 to -76.81)
-27.20
(-34.58 to -18.99)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fosamax Plus, Calcitriol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Constrained longitudinal data analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -52.03
Confidence Interval (2-Sided) 95%
-59.04 to -45.30
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Extension Study: Percentage Change From Baseline in s-P1NP at Month 12
Hide Description s-P1NP is a biochemical marker of bone turnover that is particularly useful in monitoring bone resorption, a process by which bone is broken down within the body. s-P1NP was measured at baseline and Month 12.
Time Frame Baseline and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Per-Protocol Set (PPS) population, which consisted of participants who received one dose of study treatment, had baseline measurement and had a Month 12 observation for the analysis endpoint, but excluded participants with at least one major protocol deviation.
Arm/Group Title Fosamax Plus Calcitriol
Hide Arm/Group Description:
Participants received alendronate 70 mg plus vitamin D3 5600 IU in a combination tablet (FOSAMAX PLUS D) once weekly for 6 months (base study), and then once weekly for another 6 months (extension study).
Participants received calcitriol 0.25 μg once daily orally for 6 months (base study), and then once daily orally for another 6 months (extension study).
Overall Number of Participants Analyzed 93 103
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent change
-68.07
(-70.77 to -65.11)
-17.00
(-23.79 to -9.60)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fosamax Plus, Calcitriol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Constrained longitudinal data analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -51.07
Confidence Interval (2-Sided) 95%
-57.29 to -44.99
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Extension Study: Percentage Change From Baseline in s-CTx at Month 12
Hide Description s-CTx is a biochemical marker for bone turnover that has been shown to detect increased bone resorption, a process by which bone is broken down within the body. s-CTx was measured at baseline and Month 12.
Time Frame Baseline and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Per-Protocol Set (PPS) population, which consisted of participants who received one dose of study treatment, had baseline measurement and had a Month 12 observation for the analysis endpoint, but excluded participants with at least one major protocol deviation.
Arm/Group Title Fosamax Plus Calcitriol
Hide Arm/Group Description:
Participants received alendronate 70 mg plus vitamin D3 5600 IU in a combination tablet (FOSAMAX PLUS D) once weekly for 6 months (base study), and then once weekly for another 6 months (extension study).
Participants received calcitriol 0.25 μg once daily orally for 6 months (base study), and then once daily orally for another 6 months (extension study).
Overall Number of Participants Analyzed 93 103
Least Squares Mean (95% Confidence Interval)
Unit of Measure: Percent change
-76.15
(-78.56 to -73.47)
-24.19
(-31.58 to -16.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fosamax Plus, Calcitriol
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Constrained longitudinal data analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean difference
Estimated Value -51.96
Confidence Interval (2-Sided) 95%
-58.77 to -45.39
Estimation Comments [Not Specified]
7.Other Pre-specified Outcome
Title Extension Study: Percentage of Participants With Serum 25-Hydroxyvitamin (OH) D <20 ng/mL at Month 12
Hide Description The term "vitamin D insufficiency" is used to describe vitamin D levels that are low enough to cause secondary hyperparathyroidism, bone loss, and increased risk of skeletal fracture. In this study, a threshold for vitamin D insufficiency was a level of serum 25(OH) D <20 ng/mL.
Time Frame Baseline and Month 12
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS) population, which consisted of all randomized participants who received at least one dose of study treatment, had at least one post-randomization observation for the analysis endpoint subsequent to at least one dose of study treatment, and had baseline data for analyses that required baseline data.
Arm/Group Title Fosamax Plus Calcitriol
Hide Arm/Group Description:
Participants received alendronate 70 mg plus vitamin D3 5600 IU in a combination tablet (FOSAMAX PLUS D) once weekly for 6 months (base study), and then once weekly for another 6 months (extension study).
Participants received calcitriol 0.25 μg once daily orally for 6 months (base study), and then once daily orally for another 6 months (extension study).
Overall Number of Participants Analyzed 99 105
Measure Type: Number
Unit of Measure: Percentage of Participants
4.1 47.1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Fosamax Plus, Calcitriol
Comments Odds Ratio comparison of percentage of participants with <20 ng/mL of serum 25-hydroxyvitamin (OH) D between Fosamax Plus group and Calcitriol group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.0279
Confidence Interval (2-Sided) 95%
0.0074 to 0.1048
Estimation Comments [Not Specified]
Time Frame Up to Month 12
Adverse Event Reporting Description Safety analyses for this study were performed on the all patients as treated (APaT) population, which consisted of all randomized participants who received at least one dose of study treatment.
 
Arm/Group Title Fosamax Plus Calcitriol
Hide Arm/Group Description Participants received alendronate 70 mg plus vitamin D3 5600 IU in a combination tablet (FOSAMAX PLUS D) once weekly for 6 months (base study), and then once weekly for another 6 months (extension study). Participants received calcitriol 0.25 μg once daily orally for 6 months (base study), and then once daily orally for another 6 months (extension study).
All-Cause Mortality
Fosamax Plus Calcitriol
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Fosamax Plus Calcitriol
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/107 (3.74%)      5/108 (4.63%)    
Infections and infestations     
Appendicitis  1  0/107 (0.00%)  0 1/108 (0.93%)  1
Cellulitis  1  1/107 (0.93%)  1 0/108 (0.00%)  0
Injury, poisoning and procedural complications     
Femoral neck fracture  1  0/107 (0.00%)  0 2/108 (1.85%)  2
Lumbar vertebral fracture  1  0/107 (0.00%)  0 1/108 (0.93%)  1
Spinal compression fracture  1  0/107 (0.00%)  0 1/108 (0.93%)  1
Patella fracture  1  1/107 (0.93%)  1 0/108 (0.00%)  0
Musculoskeletal and connective tissue disorders     
Spondylolisthesis  1  0/107 (0.00%)  0 1/108 (0.93%)  1
Nervous system disorders     
Cerebral infarction  1  1/107 (0.93%)  1 0/108 (0.00%)  0
Vertebrobasilar insufficiency  1  1/107 (0.93%)  1 0/108 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Fosamax Plus Calcitriol
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   39/107 (36.45%)      44/108 (40.74%)    
Gastrointestinal disorders     
Abdominal pain upper  1  9/107 (8.41%)  11 3/108 (2.78%)  3
Diarrhoea  1  4/107 (3.74%)  8 6/108 (5.56%)  7
Infections and infestations     
Nasopharyngitis  1  11/107 (10.28%)  17 13/108 (12.04%)  18
Upper respiratory tract infection  1  7/107 (6.54%)  7 6/108 (5.56%)  7
Investigations     
Urine calcium increased  1  9/107 (8.41%)  10 12/108 (11.11%)  15
Metabolism and nutrition disorders     
Vitamin D deficiency  1  0/107 (0.00%)  0 6/108 (5.56%)  6
Musculoskeletal and connective tissue disorders     
Arthralgia  1  7/107 (6.54%)  14 5/108 (4.63%)  6
Back pain  1  6/107 (5.61%)  12 3/108 (2.78%)  3
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 16.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication guidelines.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Vice President, Global Clinical Development
Organization: Merck Sharpe & Dohme Corp
Phone: 1-800-672-6372
EMail: ClinicalTrialsDisclosure@merck.com
Layout table for additonal information
Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT01350934     History of Changes
Other Study ID Numbers: 0217A-264
First Submitted: May 9, 2011
First Posted: May 10, 2011
Results First Submitted: June 20, 2014
Results First Posted: July 22, 2014
Last Update Posted: August 24, 2018