ClinicalTrials.gov
ClinicalTrials.gov Menu

A Phase II Study Evaluating SB-751689 in Post-Menopausal Women With Osteoporosis.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00471237
Recruitment Status : Terminated (Terminated for futility by sponsor after a pre-planned interim review of data)
First Posted : May 9, 2007
Results First Posted : September 5, 2017
Last Update Posted : November 7, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Osteoporosis
Interventions Drug: Ronacaleret
Drug: Teriparatide
Drug: Alendronate
Enrollment 564

Recruitment Details The study was conducted between 14-May-2007and 26-December-2008 at 45 centres in 14 countries.
Pre-assignment Details Of the 1609 participants screened, 1040 were screen failures, remaining 569 were randomized to the treatment arms. One participant from each of the 4 ronacaleret groups and alendronate group were excluded from Intent-to-Treat population and 564 participants were included in Intent-to-Treat population.
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Hide Arm/Group Description Participants received matching placebo once daily (OD) (matching to ronacaleret tablet) and matching placebo once weekly (OW) (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 milligrams (mg) and vitamin D, at least 400 international units (IU), OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 microgram (mcg), subcutaneous (SC) injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Period Title: Overall Study
Started 90 87 82 88 87 89 41
Completed 49 45 48 43 46 50 38
Not Completed 41 42 34 45 41 39 3
Reason Not Completed
Adverse Event             6             5             4             8             7             5             0
Lost to Follow-up             1             1             0             2             3             0             0
Protocol Violation             3             6             3             2             2             4             1
Withdrawal by Subject             8             6             5             8             7             4             2
Sponsor terminated study             20             23             19             22             18             24             0
Non-compliance             0             1             0             1             0             0             0
Met serum creatinine withdrawal criteria             1             0             2             2             0             0             0
Early stopping due to non-efficacy             1             0             0             0             1             0             0
Participant planned to travel to abraod             1             0             0             0             0             1             0
High parathyroid hormone             0             0             1             0             0             0             0
Participant lost medication             0             0             0             0             1             0             0
Administration of prohibited medicine             0             0             0             0             1             0             0
Participant shifted residence             0             0             0             0             1             0             0
Participant's decision             0             0             0             0             0             1             0
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD Total
Hide Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Total of all reporting groups
Overall Number of Baseline Participants 90 87 82 88 87 89 41 564
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 90 participants 87 participants 82 participants 88 participants 87 participants 89 participants 41 participants 564 participants
63.20  (6.75) 64.17  (7.69) 64.16  (7.03) 64.34  (6.57) 64.97  (7.60) 65.11  (7.04) 63.17  (5.92) 64.24  (7.04)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 90 participants 87 participants 82 participants 88 participants 87 participants 89 participants 41 participants 564 participants
Female
90
 100.0%
87
 100.0%
82
 100.0%
88
 100.0%
87
 100.0%
89
 100.0%
41
 100.0%
564
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participant
Number Analyzed 90 participants 87 participants 82 participants 88 participants 87 participants 89 participants 41 participants 564 participants
African American/African Heritage 1 2 1 0 4 1 0 9
American Indian or Alaska Native 5 5 3 3 1 4 3 24
Asian 10 7 10 11 10 8 3 59
White 73 71 66 73 71 76 35 465
African American/African Heritage & White 1 2 2 1 1 0 0 7
1.Primary Outcome
Title Percent Change From Baseline in Bone Marrow Density (BMD) at Month 12 Measured by Dual-Energy X-Ray Absorptiometry (DXA) Scans of the Lumbar Spine (L1-L4)
Hide Description DXA scanners from Hologic and GE Lunar was used to measure BMD by a DXA scan. At least two vertebrae (L1-L4) that were suitable for measurement of BMD were evaluated. The same scanner was used throughout the study for all measurements for a given participant. DXA scans were sent to a central reading facility for quality control and central analysis. Assessments performed on Day 0 were considered as Baseline. Percent change from Baseline was computed as (change from baseline / baseline value) * 100%. Percent change from Baseline in areal bone mineral density (aBMD) was reported.
Time Frame Baseline (Day 0) and 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat population comprised of any randomised or teriparatide participant who received at least one dose of study medication. Only those participants available at the specified time points were analyzed. Teriparatide arm was excluded from the analysis, since these participants were not randomized and were disproportionately represented.
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW
Hide Arm/Group Description:
Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 79 76 74 78 72 75
Least Squares Mean (Standard Error)
Unit of Measure: Percent change in BMD
0.03  (0.38) 0.32  (0.40) 1.39  (0.40) 1.61  (0.39) 1.62  (0.40) 4.54  (0.40)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 100 mg Tablet, OD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.590
Comments [Not Specified]
Method ANOVA
Comments Each dose of ronacaleret was deemed significantly different from placebo if the Hommel-adjusted p-value was <0.044 at Month 12.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
-0.78 to 1.37
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.55
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 200 mg Tablet, OD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.028
Comments [Not Specified]
Method ANOVA
Comments Each dose of ronacaleret was deemed significantly different from placebo if the Hommel-adjusted p-value was <0.044 at Month 12
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.36
Confidence Interval (2-Sided) 95%
0.28 to 2.44
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.55
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 300 mg Tablet, OD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.011
Comments [Not Specified]
Method ANOVA
Comments Each dose of ronacaleret was deemed significantly different from placebo if the Hommel-adjusted p-value was <0.044 at Month 12.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.58
Confidence Interval (2-Sided) 95%
0.51 to 2.65
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.54
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 400 mg Tablet, OD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments [Not Specified]
Method ANOVA
Comments Each dose of ronacaleret was deemed significantly different from placebo if the Hommel-adjusted p-value was <0.044 at Month 12.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.60
Confidence Interval (2-Sided) 95%
0.51 to 2.69
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.55
Estimation Comments [Not Specified]
2.Primary Outcome
Title Number of Participants With Hypercalcemia
Hide Description Participants with albumin-adjusted serum calcium pre-dose values of >11.0 mg/ deciliter (dL) or post-dose values of >12.0 mg/dL were recorded as participants with hypercalcemia. Number of participant with hypercalcemia were reported.
Time Frame Up to Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat population.
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Hide Arm/Group Description:
Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 90 87 82 88 87 89 41
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
1
   1.1%
1
   1.2%
4
   4.5%
11
  12.6%
0
   0.0%
1
   2.4%
3.Primary Outcome
Title Number of Participants Withdrew Due to Hypercalcemia
Hide Description A confirmed albumin-adjusted serum calcium pre-dose value of >11.0 mg/dL or post-dose value of >12.0 mg/dL was set as a withdrawal criteria for the study. Number of participants who met this pre-defined stopping criteria were reported.
Time Frame Up to Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat population.
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Hide Arm/Group Description:
Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 90 87 82 88 87 89 41
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
4.Primary Outcome
Title Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
Hide Description The hematology parameters analyzed were white blood cells (WBC) count with differential WBC count, red blood cells, haemoglobin, haematocrit, mean corpuscular volume and platelet count. The clinical chemistry parameters analyzed were sodium, potassium, calcium, calcium (albumin adjusted), phosphate, bicarbonate, creatinine, bilirubin (total), alanine amino transferase, aspartate amino transferase, glucose, albumin, alkaline phosphatase, creatine phosphokinase, urea, uric acid, total protein, 25-OH vitamin D, 1,25-2(OH) vitamin D, whole parathyroid hormone (PTH 1-84)) and intact PTH (1-84 and 7-84). Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important laboratory findings at any visit were reported.
Time Frame Up to Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat population.
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Hide Arm/Group Description:
Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 90 87 82 88 87 89 41
Measure Type: Count of Participants
Unit of Measure: Participants
Monocytes- high
17
  18.9%
14
  16.1%
19
  23.2%
17
  19.3%
18
  20.7%
28
  31.5%
6
  14.6%
Total neutrophils- high
9
  10.0%
11
  12.6%
10
  12.2%
10
  11.4%
4
   4.6%
6
   6.7%
4
   9.8%
Total neutrophils- low
16
  17.8%
5
   5.7%
8
   9.8%
8
   9.1%
14
  16.1%
13
  14.6%
4
   9.8%
Eosinophils- high
12
  13.3%
8
   9.2%
11
  13.4%
18
  20.5%
19
  21.8%
11
  12.4%
6
  14.6%
Glucose- high
10
  11.1%
6
   6.9%
9
  11.0%
5
   5.7%
4
   4.6%
5
   5.6%
3
   7.3%
Glucose- low
3
   3.3%
0
   0.0%
4
   4.9%
0
   0.0%
3
   3.4%
0
   0.0%
0
   0.0%
Basophils- high
2
   2.2%
0
   0.0%
1
   1.2%
0
   0.0%
1
   1.1%
1
   1.1%
0
   0.0%
Hematocrit- low
2
   2.2%
0
   0.0%
0
   0.0%
2
   2.3%
0
   0.0%
0
   0.0%
1
   2.4%
Hemoglobin- high
1
   1.1%
0
   0.0%
1
   1.2%
0
   0.0%
1
   1.1%
0
   0.0%
1
   2.4%
Hemoglobin- low
2
   2.2%
0
   0.0%
0
   0.0%
2
   2.3%
1
   1.1%
0
   0.0%
1
   2.4%
Platelets- high
2
   2.2%
0
   0.0%
1
   1.2%
0
   0.0%
0
   0.0%
1
   1.1%
0
   0.0%
White Blood Cell- high
1
   1.1%
0
   0.0%
2
   2.4%
0
   0.0%
1
   1.1%
0
   0.0%
1
   2.4%
White Blood Cell- low
1
   1.1%
1
   1.1%
0
   0.0%
2
   2.3%
0
   0.0%
0
   0.0%
0
   0.0%
Calcium- high
0
   0.0%
0
   0.0%
1
   1.2%
1
   1.1%
1
   1.1%
0
   0.0%
0
   0.0%
Phosphorus- high
1
   1.1%
0
   0.0%
0
   0.0%
1
   1.1%
0
   0.0%
0
   0.0%
1
   2.4%
Alkaline Phosphatase- high
0
   0.0%
1
   1.1%
0
   0.0%
3
   3.4%
3
   3.4%
1
   1.1%
0
   0.0%
Total bilirubin- high
0
   0.0%
1
   1.1%
2
   2.4%
1
   1.1%
1
   1.1%
0
   0.0%
0
   0.0%
5.Primary Outcome
Title Number of Participant With Vital Signs of Potential Clinical Concern at Any Post-baseline Visit
Hide Description The potential clinical importance ranges (low and high) of the vital sign parameters-systolic blood pressure (> 30 millimeter of mercury [mmHg] decrease from Baseline, > 30 mmHg increase from Baseline), diastolic blood pressure (> 20 mmHg decrease from Baseline and > 20 mmHg increase from Baseline) and heart rate (<45 and >120 beats per minute). Only those parameters for which at least one value of potential clinical importance was reported are summarized. The number of participants with potential clinical important vital parameter findings at any visit were reported.
Time Frame Up to 12 Months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat population.
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Hide Arm/Group Description:
Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 90 87 82 88 87 89 41
Measure Type: Count of Participants
Unit of Measure: Participants
Systolic Blood Pressure, High Number Analyzed 87 participants 85 participants 82 participants 87 participants 87 participants 89 participants 40 participants
5
   5.7%
10
  11.8%
8
   9.8%
9
  10.3%
11
  12.6%
8
   9.0%
1
   2.5%
Systolic Blood Pressure, Low Number Analyzed 87 participants 85 participants 82 participants 87 participants 87 participants 89 participants 40 participants
6
   6.9%
8
   9.4%
10
  12.2%
6
   6.9%
4
   4.6%
8
   9.0%
3
   7.5%
Diastolic Blood Pressure, High Number Analyzed 87 participants 85 participants 82 participants 87 participants 87 participants 89 participants 40 participants
2
   2.3%
6
   7.1%
5
   6.1%
1
   1.1%
6
   6.9%
3
   3.4%
1
   2.5%
Diastolic Blood Pressure, Low Number Analyzed 87 participants 85 participants 82 participants 87 participants 87 participants 89 participants 40 participants
8
   9.2%
9
  10.6%
4
   4.9%
12
  13.8%
10
  11.5%
10
  11.2%
2
   5.0%
Heart Rate, Low Number Analyzed 87 participants 85 participants 82 participants 87 participants 87 participants 89 participants 40 participants
2
   2.3%
0
   0.0%
1
   1.2%
1
   1.1%
1
   1.1%
0
   0.0%
0
   0.0%
6.Primary Outcome
Title Number of Participant With Electrocardiogram (ECG) Findings Reported as Adverse Event
Hide Description Full 12-lead ECGs pre-dose at screening and visits 6, 8, 11, 12 and 14 were recorded. Participants rested supine or seated for at least 10 minutes before each reading. All ECGs were transmitted to a central reviewer for blinded assessment. The central reviewer measured the following parameters and provide a clinical interpretation: heart rate, RR interval, PR interval, QRS interval, QT (uncorrected) interval, QTcB (Bazett’s correction) interval, QTcF (Fridericia’s correction) interval. The central reviewer was provided the investigator or designated qualified site physician with a central ECG report or confirmatory report to assist them in identifying any clinically significant abnormalities that would preclude the participant from further participation in the study.
Time Frame Up to 12 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat population.
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Hide Arm/Group Description:
Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 90 87 82 88 87 89 41
Measure Type: Count of Participants
Unit of Measure: Participants
1
   1.1%
5
   5.7%
4
   4.9%
3
   3.4%
3
   3.4%
5
   5.6%
0
   0.0%
7.Primary Outcome
Title Mean Change From Baseline in Height
Hide Description Assessments performed on Day 0 were considered as Baseline. Change from Baseline was computed as values at post baseline visit minus Baseline value. Mean change from baseline in height at Month 6 and 12 and early withdrawal were reported.
Time Frame Baseline (Day 0), Month 6, 12 and early withdrawal
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Hide Arm/Group Description:
Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 90 87 82 88 87 89 41
Mean (Standard Deviation)
Unit of Measure: Centimeter
Month 6 Number Analyzed 68 participants 70 participants 68 participants 75 participants 70 participants 74 participants 38 participants
-0.04  (0.58) 0.17  (1.41) 0.72  (3.82) 0.05  (0.70) -0.04  (0.82) -0.07  (1.13) 0.11  (0.65)
Month 12 Number Analyzed 49 participants 45 participants 48 participants 43 participants 41 participants 50 participants 38 participants
-0.14  (0.65) 0.04  (1.59) 0.02  (0.76) -0.09  (1.04) -0.17  (0.67) -0.08  (0.57) 0.11  (0.56)
Early withdrawal Number Analyzed 36 participants 36 participants 32 participants 37 participants 31 participants 35 participants 2 participants
0.03  (0.61) 0.17  (1.92) -0.13  (0.55) -0.16  (0.76) -0.16  (0.82) -0.37  (0.88) 0  (0)
8.Primary Outcome
Title Mean Change From Baseline in Weight
Hide Description Baseline values were assessed on Day 0. Change from Baseline was computed as values at post baseline visit minus Baseline value. Mean change from baseline in weight at Month 6, 12 and early withdrawal were reported.
Time Frame Baseline (Day 0), Month 6, 12 and early withdrawal
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Hide Arm/Group Description:
Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 90 87 82 88 87 89 41
Mean (Standard Deviation)
Unit of Measure: Kilogram
Month 6 Number Analyzed 69 participants 70 participants 68 participants 75 participants 70 participants 74 participants 38 participants
-0.02  (2.12) 0.27  (3.27) 0.45  (2.98) -0.24  (2.87) 0.11  (2.84) 0.29  (1.89) 0.51  (1.84)
Month 12 Number Analyzed 49 participants 45 participants 48 participants 43 participants 47 participants 50 participants 38 participants
0.32  (2.73) -0.72  (2.70) 1.18  (9.78) -0.22  (2.36) -0.48  (2.28) 0.57  (3.22) 0.09  (2.45)
Early withdrawal Number Analyzed 36 participants 36 participants 32 participants 37 participants 32 participants 35 participants 2 participants
-0.45  (2.40) 0.40  (4.60) -0.34  (2.48) 0.37  (3.86) 0.00  (2.17) -0.12  (2.33) -2.15  (1.48)
9.Secondary Outcome
Title Percent Change From Baseline to Month 6 in BMD Measured by DXA Scans of the Lumbar Spine (L1-L4)
Hide Description DXA scanners from Hologic and GE Lunar was used to measure BMD by a DXA scan. At least two vertebrae (L1-L4) that were suitable for measurement of BMD were evaluated. The same scanner was used throughout the study for all measurements for a given participant. DXA scans were sent to a central reading facility for quality control and central analysis. Baseline values were assessed on Day 0. Percent Change from Baseline was computed as (change from baseline / baseline value) * 100%. Percent change from baseline to month 6 in aBMD was reported.
Time Frame Baseline (Day 0) and Month 6
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat Population. Only those participants available at the specified time point were analyzed. Participants from Teriparatide, 20 mcg, SC injection, OD arm were excluded from the analysis, since these participants were not randomized and were disproportionately represented.
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW
Hide Arm/Group Description:
Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 79 76 74 77 73 75
Least Squares Mean (Standard Error)
Unit of Measure: percent change in BMD
0.66  (0.33) 0.21  (0.34) 1.61  (0.35) 0.47  (0.34) 1.01  (0.35) 3.42  (0.34)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 100 mg Tablet, OD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.680
Comments [Not Specified]
Method ANOVA
Comments Each dose of ronacaleret was deemed significantly different from placebo if the Hommel-adjusted p-value was <0.006 at Month 6.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.45
Confidence Interval (2-Sided) 95%
-1.38 to 0.48
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.47
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 200 mg Tablet, OD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.192
Comments [Not Specified]
Method ANOVA
Comments Each dose of ronacaleret was deemed significantly different from placebo if the Hommel-adjusted p-value was <0.006 at Month 6.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.95
Confidence Interval (2-Sided) 95%
0.01 to 1.89
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.48
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 300 mg Tablet, OD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.680
Comments [Not Specified]
Method ANOVA
Comments Each dose of ronacaleret was deemed significantly different from placebo if the Hommel-adjusted p-value was <0.006 at Month 6.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-1.12 to 0.73
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.47
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 400 mg Tablet, OD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.680
Comments [Not Specified]
Method ANOVA
Comments Each dose of ronacaleret was deemed significantly different from placebo if the Hommel-adjusted p-value was <0.006 at Month 6.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
-0.59 to 1.29
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.48
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percent Change From Baseline to Months 6 and 12 in BMD Measured by DXA Scans of the Hip (Total Hip, Femoral Neck and Trochanter).
Hide Description DXA scanners from Hologic and GE Lunar was used to measure BMD by a DXA scan. At least two vertebrae (L1-L4) that were suitable for measurement of BMD were evaluated. The same scanner was used throughout the study for all measurements for a given participant. DXA scans were sent to a central reading facility for quality control and central analysis. Baseline values were assessed on Day 0. Percent Change from Baseline was computed as (change from baseline / baseline value) * 100%. Percent change from baseline to month 6 and 12 in aBMD of hip (total hip, femoral neck and trochanter) were reported.
Time Frame Baseline (Day 0), Month 6 and Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat population. Only those participants available at the specified time points were analyzed. Participants from Teriparatide, 20 mcg, SC injection, OD arm were excluded from the analysis, since these participants were not randomized and were disproportionately represented.
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW
Hide Arm/Group Description:
Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 90 87 82 88 87 89
Least Squares Mean (Standard Error)
Unit of Measure: Percent change in BMD
Total Hip aBMD, Month 6 Number Analyzed 79 participants 75 participants 74 participants 77 participants 71 participants 74 participants
0.42  (0.23) -0.26  (0.24) -0.37  (0.24) -0.86  (0.23) -0.88  (0.24) 1.84  (0.24)
Total Hip aBMD, Month 12 Number Analyzed 79 participants 75 participants 74 participants 78 participants 70 participants 74 participants
0.27  (0.26) -0.62  (0.26) -0.75  (0.27) -1.07  (0.26) -1.31  (0.27) 2.70  (0.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 100 mg Tablet, OD
Comments Total Hip aBMD, Month 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.037
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.68
Confidence Interval (2-Sided) 95%
-1.32 to -0.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.33
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 200 mg Tablet, OD
Comments Total Hip aBMD, Month 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.017
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.79
Confidence Interval (2-Sided) 95%
-1.43 to -0.14
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.33
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 300 mg Tablet, OD
Comments Total Hip aBMD, Month 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.000
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.28
Confidence Interval (2-Sided) 95%
-1.92 to -0.64
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.32
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 400 mg Tablet, OD
Comments Total Hip aBMD, Month 6
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.000
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.30
Confidence Interval (2-Sided) 95%
-1.95 to -0.65
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.33
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 100 mg Tablet, OD
Comments Total Hip aBMD, Month 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.015
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.89
Confidence Interval (2-Sided) 95%
-1.61 to -0.17
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 200 mg Tablet, OD
Comments Total Hip aBMD, Month 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.02
Confidence Interval (2-Sided) 95%
-1.74 to -0.30
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.37
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 300 mg Tablet, OD
Comments Total Hip aBMD, Month 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.000
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.33
Confidence Interval (2-Sided) 95%
-2.04 to -0.63
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.36
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Placebo, Ronacaleret, 400 mg Tablet, OD
Comments Total Hip aBMD, Month 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.000
Comments [Not Specified]
Method ANOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value -1.57
Confidence Interval (2-Sided) 95%
-2.30 to -0.84
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.37
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Number of Participants Who Remained the Same or Had Any Improvement in DXA BMD (> Baseline)
Hide Description Responder rate of participants who remained the same or had any improvement as compared to baseline in DXA BMD of vertebra, femur and vertebra plus femur were reported. Baseline values were assessed on Day 0. Percent change (improvement) from Baseline was computed as (change from baseline / baseline value) * 100%.
Time Frame Baseline (Day 0), Month 5, 6 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Hide Arm/Group Description:
Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 90 87 82 88 87 89 41
Measure Type: Count of Participants
Unit of Measure: Participants
Month 5, Vertebra, BMD % change >=0 Number Analyzed 1 participants 0 participants 1 participants 0 participants 1 participants 0 participants 0 participants
0
   0.0%
0
1
 100.0%
0
1
 100.0%
0 0
Month 5, Femur, BMD % change >=0 Number Analyzed 0 participants 0 participants 1 participants 0 participants 0 participants 0 participants 0 participants
0 0
1
 100.0%
0 0 0 0
Month 5, Vertebra + Femur, BMD % change >=0 Number Analyzed 0 participants 0 participants 1 participants 0 participants 0 participants 0 participants 0 participants
0 0
1
 100.0%
0 0 0 0
Month 6, Vertebra, BMD % change >=0 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 1 participants 0 participants
0 0 0 0 0
1
 100.0%
0
Month 6, Femur, BMD % change >=0 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 1 participants 0 participants
0 0 0 0 0
1
 100.0%
0
Month 6, Vertebra + Femur, BMD % change >=0 Number Analyzed 0 participants 0 participants 0 participants 0 participants 0 participants 1 participants 0 participants
0 0 0 0 0
1
 100.0%
0
Month 12, Vertebra, BMD % change >=0 Number Analyzed 42 participants 50 participants 43 participants 43 participants 41 participants 49 participants 36 participants
16
  38.1%
29
  58.0%
32
  74.4%
35
  81.4%
31
  75.6%
44
  89.8%
34
  94.4%
Month 12, Femur, BMD % change >=0 Number Analyzed 41 participants 47 participants 40 participants 39 participants 37 participants 45 participants 26 participants
20
  48.8%
23
  48.9%
14
  35.0%
19
  48.7%
16
  43.2%
40
  88.9%
25
  96.2%
Month 12, Vertebra + Femur, BMD % change >=0 Number Analyzed 39 participants 47 participants 40 participants 39 participants 37 participants 42 participants 25 participants
10
  25.6%
19
  40.4%
12
  30.0%
17
  43.6%
16
  43.2%
35
  83.3%
24
  96.0%
Early Withdrawal, Vertebra, BMD % change >=0 Number Analyzed 3 participants 2 participants 2 participants 3 participants 1 participants 0 participants 1 participants
1
  33.3%
1
  50.0%
1
  50.0%
2
  66.7%
1
 100.0%
0
1
 100.0%
Early Withdrawal, Femur, BMD % change >=0 Number Analyzed 2 participants 2 participants 2 participants 3 participants 1 participants 0 participants 1 participants
1
  50.0%
1
  50.0%
0
   0.0%
1
  33.3%
1
 100.0%
0
1
 100.0%
Early Withdrawal, Vertebra + Femur, BMD %change>=0 Number Analyzed 2 participants 2 participants 2 participants 3 participants 1 participants 0 participants 1 participants
1
  50.0%
1
  50.0%
0
   0.0%
1
  33.3%
1
 100.0%
0
1
 100.0%
12.Secondary Outcome
Title Percent Change From Baseline to Month 12 in the Volumetric Integral, Cortical, and Trabecular Density (BMD) at the Hip and Lumbar Spine as Measured by Quantitative Computer Tomography (QCT) Scans
Hide Description QCT is a three-dimensional non-projectional technique to quantify BMD with a number of advantages to other densitometric techniques. Cortical and trabecular bone can be separated, trabecular volume of interest (VOI) are largely independent of degenerative changes in the spine and 3 dimensional geometric parameters can be determined. BMD as measured by QCT is a true density measured in g/cm^3 in contrast to DXA Which determines an areal density measured in g/cm^2. Baseline values were assessed on Day 0. Percent change from Baseline was computed as (change from baseline / baseline value) * 100%. Percent change from Baseline to month 12 in the volumetric integral, cortical, and trabecular density (BMD) at the hip and lumbar spine measured by QCT were reported.
Time Frame Baseline (Day 0) and Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Hide Arm/Group Description:
Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 90 87 82 88 87 89 41
Mean (Standard Deviation)
Unit of Measure: Percent change in BMD
Total vertebra integral VOI BMD Number Analyzed 42 participants 50 participants 43 participants 43 participants 41 participants 49 participants 36 participants
-0.98  (3.13) 1.09  (4.01) 3.00  (4.98) 3.91  (4.98) 4.83  (6.56) 5.04  (4.39) 14.80  (8.69)
Mid vertebra integral VOI BMD Number Analyzed 42 participants 50 participants 43 participants 43 participants 41 participants 49 participants 36 participants
-1.31  (3.54) 1.20  (4.85) 4.65  (5.87) 6.06  (6.48) 7.33  (8.67) 4.85  (5.25) 17.97  (11.27)
Mid Cylinder trabecular VOI BMD Number Analyzed 42 participants 50 participants 43 participants 43 participants 41 participants 49 participants 36 participants
-2.45  (4.39) 1.75  (8.70) 6.17  (10.37) 8.99  (10.52) 13.29  (15.32) 4.88  (7.68) 24.37  (15.92)
Mid Osteo trabecular VOI BMD Number Analyzed 42 participants 50 participants 43 participants 43 participants 41 participants 49 participants 36 participants
-2.21  (4.58) 1.81  (8.26) 7.06  (9.25) 9.54  (9.79) 13.21  (14.68) 5.15  (6.86) 24.21  (15.80)
Total vertebra trabecular VOI BMD Number Analyzed 42 participants 50 participants 43 participants 43 participants 41 participants 49 participants 36 participants
-2.46  (4.58) 1.67  (7.18) 5.81  (8.31) 8.52  (8.97) 11.40  (12.83) 4.97  (6.43) 23.82  (14.64)
Mid Osteo cortical VOI BMD Number Analyzed 42 participants 50 participants 43 participants 43 participants 41 participants 49 participants 36 participants
-0.30  (4.69) 0.63  (4.80) 2.37  (6.37) 2.57  (5.14) 1.22  (4.39) 4.98  (4.63) 9.25  (7.68)
13.Secondary Outcome
Title Percent Change From Baseline to Month 12 in the Total Vertebra Integral VOI at the Lumbar Spine as Measured by QCT Scans
Hide Description QCT is a three-dimensional non-projectional technique to quantify BMD with a number of advantages to other densitometric techniques. Cortical and trabecular bone can be separated, trabecular VOI are largely independent of degenerative changes in the spine and 3 dimensional geometric parameters can be determined. BMD as measured by QCT is a true density measured in g/cm^3 in contrast to DXA Which determines an areal density measured in g/cm^2. Baseline values were assessed on Day 0. Percent change from Baseline was computed as (change from baseline / baseline value) * 100%.
Time Frame Baseline (Day 0) and Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Hide Arm/Group Description:
Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 42 50 43 43 41 49 36
Mean (Standard Deviation)
Unit of Measure: Percent change in VOI
0.04  (4.19) 0.85  (4.14) 3.01  (5.18) 3.58  (5.70) 3.54  (5.64) 5.39  (5.87) 12.23  (8.43)
14.Secondary Outcome
Title Percent Change From Baseline to Month 12 in the Volumetric Integral, Cortical, and Trabecular Density (BMD) at the Hip as Measured by QCT Scans
Hide Description QCT is a three-dimensional non-projectional technique to quantify BMD with a number of advantages to other densitometric techniques. Cortical and trabecular bone can be separated, trabecular VOI are largely independent of degenerative changes in the spine and 3 dimensional geometric parameters can be determined. BMD as measured by QCT is a true density measured in mg/cm^3 in contrast to DXA Which determines an areal density measured in g/cm^2. Baseline values were assessed on Day 0. Percent change from Baseline was computed as (change from baseline / baseline value) * 100%.
Time Frame Baseline (Day 0) and Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Hide Arm/Group Description:
Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 41 47 40 39 37 45 26
Mean (Standard Deviation)
Unit of Measure: Percent change in BMD
Femur integral VOI BMD 0.02  (2.78) -0.05  (2.67) -0.81  (2.80) -0.53  (2.18) -0.15  (2.98) 2.70  (2.13) 3.92  (2.67)
Femur trabecular VOI BMD -0.36  (5.53) -0.40  (6.81) -2.16  (7.39) 1.16  (5.06) 2.81  (8.20) 3.05  (5.92) 13.19  (8.96)
Femur cortical VOI BMD 1.11  (4.04) -0.32  (2.90) -1.46  (2.81) -1.06  (2.53) -1.79  (3.01) 2.44  (3.13) 0.22  (2.63)
Neck integral VOI BMD -0.10  (2.48) 0.16  (2.83) -0.94  (3.34) -1.20  (2.99) -1.45  (3.22) 1.65  (2.72) 2.06  (3.65)
Neck trabecular VOI BMD -0.95  (7.44) -2.19  (7.91) -2.68  (6.14) 1.35  (9.91) 3.05  (11.18) 2.77  (7.55) 11.27  (10.31)
Neck cortical VOI BMD 1.23  (4.55) 0.44  (4.16) -1.67  (3.95) -1.85  (3.89) -2.80  (4.55) 1.10  (4.25) -0.69  (4.49)
Trochanter integral VOI BMD -0.58  (3.88) -0.16  (4.22) -1.53  (3.92) -1.16  (3.29) -0.98  (3.83) 3.15  (3.27) 4.96  (4.74)
Trochanter trabecular VOI BMD -1.62  (9.67) -1.34  (13.50) -2.54  (11.05) 2.12  (8.82) 2.10  (10.66) 3.55  (7.55) 14.12  (14.51)
Trochanter cortical VOI BMD 0.56  (5.29) -0.70  (4.08) -1.53  (3.60) -1.48  (3.53) -2.59  (4.04) 3.33  (3.57) 1.99  (4.37)
15.Secondary Outcome
Title Percent Change From Baseline to Month 12 in Cortical Thickness at the Hip as Measured by QCT Scans
Hide Description Percent change in thickness of femur neck cortical VOI thickness and trochanter cortical VOI thickness were at Month 12 measured by QCT were reported. Assessments performed on Day 0 were considered as Baseline. Percent change from Baseline was computed as (change from baseline / baseline value) * 100%.
Time Frame Baseline (Day 0) and Month 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Hide Arm/Group Description:
Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 41 47 40 39 37 45 26
Mean (Standard Deviation)
Unit of Measure: Percent change in cortical thickness
Neck cortical VOI Thickness -0.85  (7.09) -0.13  (5.98) 1.12  (5.75) -0.88  (4.73) 0.32  (4.93) -0.13  (5.98) 0.39  (4.36)
Trochanter cortical VOI Thickness -1.00  (5.85) 0.76  (4.40) 1.01  (5.15) -0.82  (3.65) 1.60  (3.70) 0.81  (5.39) 0.76  (2.93)
16.Secondary Outcome
Title Biochemical Markers of Bone Turnover: Levels of C-terminal Telopeptide α1 Chain of Type 1 Collagen (CTX1)
Hide Description Blood samples were collected at Baseline (Day 0), Week 4, Month 3, 6, and 12 for measurement of CTX1.
Time Frame Baseline (Day 0), Week 4, Month 3, 6, and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Hide Arm/Group Description:
Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 90 87 82 88 87 89 41
Least Squares Mean (Standard Error)
Unit of Measure: nanogram per litre (ng/L)
Baseline Number Analyzed 88 participants 82 participants 81 participants 87 participants 84 participants 87 participants 41 participants
625.2  (1.05) 635.3  (1.05) 632.0  (1.05) 587.9  (1.05) 645.5  (1.05) 630.4  (1.05) 564.0  (1.07)
Baseline, Placebo contrast Number Analyzed 0 participants 82 participants 81 participants 87 participants 84 participants 87 participants 41 participants
1.02  (1.07) 1.01  (1.07) 0.94  (1.07) 1.03  (1.07) 1.01  (1.07) 0.90  (1.09)
Week 4 Number Analyzed 76 participants 78 participants 76 participants 83 participants 78 participants 63 participants 38 participants
530.7  (1.05) 515.2  (1.05) 525.4  (1.05) 506.1  (1.05) 529.2  (1.05) 288.0  (1.06) 576.1  (1.08)
Week 4, Placebo contrast Number Analyzed 0 participants 78 participants 76 participants 83 participants 78 participants 63 participants 38 participants
0.97  (1.08) 0.99  (1.08) 0.95  (1.08) 1.00  (1.08) 0.54  (1.08) 1.09  (1.10)
Month 3 Number Analyzed 76 participants 73 participants 71 participants 75 participants 72 participants 49 participants 40 participants
523.5  (1.05) 598.5  (1.06) 688.9  (1.06) 723.2  (1.05) 818.9  (1.06) 257.1  (1.06) 864.1  (1.08)
Month 3, Placebo contrast Number Analyzed 0 participants 73 participants 71 participants 75 participants 72 participants 49 participants 40 participants
1.14  (1.08) 1.32  (1.08) 1.38  (1.08) 1.56  (1.08) 0.49  (1.08) 1.65  (1.10)
Month 6 Number Analyzed 69 participants 70 participants 66 participants 73 participants 70 participants 34 participants 37 participants
517.6  (1.06) 648.2  (1.06) 777.1  (1.06) 859.6  (1.06) 964.3  (1.06) 235.9  (1.07) 1112  (1.08)
Month 6, Placebo contrast Number Analyzed 0 participants 70 participants 66 participants 73 participants 70 participants 34 participants 37 participants
1.25  (1.08) 1.50  (1.08) 1.66  (1.08) 1.86  (1.08) 0.46  (1.09) 2.15  (1.10)
Month 12 Number Analyzed 50 participants 44 participants 49 participants 40 participants 49 participants 50 participants 37 participants
525.1  (1.08) 695.2  (1.08) 806.1  (1.08) 852.8  (1.08) 991.9  (1.08) 158.3  (1.08) 1071  (1.10)
Month 12, Placebo contrast Number Analyzed 0 participants 44 participants 49 participants 40 participants 49 participants 50 participants 37 participants
1.32  (1.12) 1.54  (1.11) 1.62  (1.12) 1.89  (1.11) 0.30  (1.11) 2.04  (1.13)
17.Secondary Outcome
Title Biochemical Markers of Bone Turnover: Procollagen Type 1 N-terminal Propeptide (P1NP)
Hide Description Blood samples were collected at Baseline (Day 0), Week 4, Month 3, 6, and 12 for measurement of P1NP.
Time Frame Baseline (Day 0), Week 4, Month 3, 6, and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent to treat population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Hide Arm/Group Description:
Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 90 87 82 88 87 89 41
Least Squares Mean (Standard Error)
Unit of Measure: Microgram per Litre (mcg/L)
Baseline Number Analyzed 86 participants 83 participants 81 participants 87 participants 83 participants 88 participants 41 participants
47.66  (1.05) 45.59  (1.05) 47.70  (1.05) 46.62  (1.05) 46.19  (1.05) 47.71  (1.05) 48.57  (1.07)
Baseline, Placebo contrast Number Analyzed 0 participants 83 participants 81 participants 87 participants 83 participants 88 participants 41 participants
0.96  (1.07) 1.00  (1.07) 0.98  (1.07) 0.97  (1.07) 1.00  (1.07) 1.02  (1.08)
Week 4 Number Analyzed 80 participants 78 participants 75 participants 85 participants 79 participants 81 participants 39 participants
45.32  (1.05) 49.67  (1.05) 57.36  (1.05) 60.27  (1.05) 63.46  (1.05) 43.66  (1.05) 92.74  (1.07)
Week 4, Placebo contrast Number Analyzed 0 participants 78 participants 75 participants 85 participants 79 participants 81 participants 39 participants
1.10  (1.07) 1.27  (1.07) 1.33  (1.07) 1.40  (1.07) 0.96  (1.07) 2.05  (1.09)
Month 3 Number Analyzed 77 participants 72 participants 72 participants 76 participants 73 participants 79 participants 40 participants
39.53  (1.05) 49.99  (1.05) 65.21  (1.05) 73.68  (1.05) 86.84  (1.05) 20.15  (1.05) 99.74  (1.08)
Month 3, Placebo contrast Number Analyzed 0 participants 72 participants 72 participants 76 participants 73 participants 79 participants 40 participants
1.26  (1.08) 1.65  (1.08) 1.86  (1.08) 2.20  (1.08) 0.51  (1.07) 2.52  (1.09)
Month 6 Number Analyzed 69 participants 70 participants 67 participants 72 participants 70 participants 74 participants 38 participants
38.41  (1.05) 56.37  (1.05) 75.73  (1.06) 90.55  (1.05) 104.6  (1.05) 16.41  (1.05) 117.8  (1.08)
Month 6, Placebo contrast Number Analyzed 0 participants 70 participants 67 participants 72 participants 70 participants 74 participants 38 participants
1.47  (1.08) 1.97  (1.08) 2.36  (1.08) 2.72  (1.08) 0.43  (1.08) 3.07  (1.09)
Month 12 Number Analyzed 50 participants 44 participants 50 participants 40 participants 49 participants 51 participants 37 participants
40.74  (1.05) 61.43  (1.05) 82.69  (1.05) 98.04  (1.05) 112.6  (1.05) 16.98  (1.05) 119.0  (1.07)
Month 12, Placebo contrast Number Analyzed 0 participants 44 participants 50 participants 40 participants 49 participants 51 participants 37 participants
1.51  (1.08) 2.03  (1.08) 2.41  (1.08) 2.76  (1.08) 0.42  (1.08) 2.92  (1.09)
18.Secondary Outcome
Title Biochemical Markers of Bone Turnover: Bone Specific Alkaline Phosphatase (BALP)
Hide Description Blood samples were collected at Baseline (Day 0), Week 4, Month 3, 6, and 12 for measurement of BALP.
Time Frame Baseline (Day 0), Week 4, Month 3, 6, and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Hide Arm/Group Description:
Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 90 87 82 88 87 89 41
Least Squares Mean (Standard Error)
Unit of Measure: mcg/L
Baseline Number Analyzed 89 participants 84 participants 81 participants 88 participants 86 participants 89 participants 41 participants
14.46  (1.04) 14.96  (1.04) 14.24  (1.04) 15.06  (1.04) 14.12  (1.04) 14.31  (1.04) 14.50  (1.05)
Baseline, Placebo contrast Number Analyzed 0 participants 84 participants 81 participants 88 participants 86 participants 89 participants 41 participants
1.03  (1.05) 0.98  (1.05) 1.04  (1.05) 0.98  (1.05) 0.99  (1.05) 1.00  (1.07)
Week 4 Number Analyzed 79 participants 79 participants 76 participants 85 participants 79 participants 83 participants 39 participants
14.02  (1.04) 14.72  (1.04) 14.51  (1.04) 15.97  (1.04) 15.72  (1.04) 13.68  (1.04) 16.19  (1.06)
Week 4, Placebo contrast Number Analyzed 0 participants 79 participants 76 participants 85 participants 79 participants 83 participants 39 participants
1.05  (1.05) 1.03  (1.06) 1.14  (1.05) 1.12  (1.05) 0.98  (1.05) 1.15  (1.07)
Month 3 Number Analyzed 77 participants 73 participants 71 participants 75 participants 73 participants 78 participants 40 participants
12.66  (1.04) 15.23  (1.04) 15.44  (1.04) 18.77  (1.04) 17.85  (1.04) 9.44  (1.04) 16.53  (1.06)
Month 3, Placebo contrast Number Analyzed 0 participants 73 participants 71 participants 75 participants 73 participants 78 participants 40 participants
1.20  (1.06) 1.22  (1.06) 1.48  (1.06) 1.41  (1.06) 0.75  (1.06) 1.31  (1.07)
Month 6 Number Analyzed 69 participants 71 participants 67 participants 73 participants 70 participants 74 participants 37 participants
12.81  (1.04) 16.31  (1.04) 17.43  (1.04) 22.18  (1.04) 21.47  (1.04) 8.36  (1.04) 17.63  (1.06)
Month 6, Placebo contrast Number Analyzed 0 participants 71 participants 67 participants 73 participants 70 participants 74 participants 37 participants
1.27  (1.06) 1.36  (1.06) 1.73  (1.06) 1.68  (1.06) 0.65  (1.06) 1.38  (1.07)
Month 12 Number Analyzed 50 participants 44 participants 50 participants 40 participants 48 participants 50 participants 37 participants
13.25  (1.04) 16.64  (1.04) 18.80  (1.04) 23.36  (1.04) 23.28  (1.04) 8.42  (1.04) 19.08  (1.06)
Month 12, Placebo contrast Number Analyzed 0 participants 44 participants 50 participants 40 participants 48 participants 50 participants 37 participants
1.26  (1.06) 1.42  (1.06) 1.76  (1.06) 1.76  (1.06) 0.64  (1.06) 1.44  (1.07)
19.Secondary Outcome
Title Blood Concentrations of Ronacaleret
Hide Description Blood samples were collected and analyzed for concentrations of ronacaleret. The individual blood concentration-time data from the intensive PK-PD subgroup of participants were analyzed by standard noncompartmental methods. Blood concentrations of ronacaleret were reported.
Time Frame Pre-dose (0.0 hour [h]) and 12 h post dose at Week 4, 20, 40 min, 1, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 1-4, 8-12, and 24 h at Month 3, 6 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Concentration Population comprised of any Intent-to-Treat participants for whom a SB-751689 pharmacokinetic blood sample was obtained and analyzed. Only those participants available at the specified time points were analyzed.
Arm/Group Title Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD
Hide Arm/Group Description:
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 76 74 80 78
Mean (Standard Deviation)
Unit of Measure: nanograms per millilitre (ng/mL)
Week 4, Pre-dose Number Analyzed 67 participants 65 participants 73 participants 71 participants
41.22  (127.438) 37.24  (36.203) 85.44  (158.849) 79.40  (74.083)
Week 4, 8-12 h post dose Number Analyzed 66 participants 64 participants 72 participants 70 participants
204.82  (183.245) 328.33  (222.061) 581.08  (360.031) 685.14  (450.467)
Month 6, Pre-dose Number Analyzed 66 participants 61 participants 70 participants 67 participants
21.37  (19.769) 65.94  (214.325) 74.12  (146.094) 117.94  (288.413)
Month 6, 1-4 h post dose Number Analyzed 49 participants 45 participants 51 participants 53 participants
644.90  (408.282) 1308.35  (943.397) 1610.74  (1016.608) 2054.71  (1499.079)
Month 6, 8-12 h post dose Number Analyzed 52 participants 45 participants 53 participants 54 participants
186.69  (101.326) 385.03  (284.963) 576.35  (382.494) 796.99  (640.016)
Month 6, 24 h post dose Number Analyzed 13 participants 14 participants 14 participants 11 participants
186.21  (151.855) 290.74  (125.486) 578.63  (398.915) 473.41  (237.671)
Month 12, Pre-dose Number Analyzed 43 participants 43 participants 38 participants 42 participants
20.68  (15.971) 33.47  (26.747) 147.63  (370.860) 114.83  (179.448)
Month 12, 1-4 h post dose Number Analyzed 28 participants 28 participants 28 participants 31 participants
779.92  (465.356) 999.63  (659.880) 1819.53  (1021.984) 2128.24  (1549.003)
Month 12, 8-12 h post dose Number Analyzed 30 participants 28 participants 27 participants 30 participants
203.39  (124.866) 262.20  (137.152) 651.95  (391.752) 740.18  (679.348)
Month 12, 24 h post dose Number Analyzed 12 participants 14 participants 9 participants 11 participants
187.23  (100.001) 297.20  (146.806) 626.72  (231.777) 512.65  (314.692)
20.Secondary Outcome
Title Area Under the Concentration-time Curve Over the Dosing Interval (AUC 0-t) and Area Under the Concentration-time Curve Over the Dosing Interval (AUC 0-tau) of Ronacaleret
Hide Description Blood samples were collected and analyzed for concentrations of ronacaleret. The individual blood concentration-time data from the intensive pharmacokinetic and pharmacodynamics subgroup of participants were analyzed by standard noncompartmental methods. Blood samples were collected and analyzed for concentrations of ronacaleret. The individual blood concentration-time data from the intensive PK-PD subgroup of participants were analyzed by standard noncompartmental methods. Following log transformation, AUC(0-t) and AUC(0-τ) of ronacaleret were separately analyzed by ANOVA using mixed effects model, fitting treatment and country/region as fixed effects.
Time Frame Pre-dose (0.0 h) and 12 h post dose at Week 4, 20, 40 min, 1, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 1-4, 8-12, and 24 h at Month 3, 6 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic Parameters Population comprised of any participant in the pharmacokinetic concentration population who provided pharmacokinetic parameters. Only those participants available at the specified time points were analyzed.
Arm/Group Title Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD
Hide Arm/Group Description:
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 13 14 14 11
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanogram*hour per millilitre (ng*hr/mL)
AUC 0-t, Month 6 Number Analyzed 13 participants 14 participants 14 participants 11 participants
2495.8751
(53.13%)
4575.8746
(35.50%)
7545.3302
(42.26%)
6712.0537
(79.69%)
AUC 0-t, Month 12 Number Analyzed 12 participants 14 participants 9 participants 11 participants
2766.6822
(64.20%)
4548.6490
(43.87%)
9259.3127
(37.74%)
6798.4219
(65.17%)
AUC 0-tau, Month 6 Number Analyzed 13 participants 14 participants 14 participants 11 participants
3628.0901
(66.72%)
6428.5540
(36.62%)
10825.9083
(50.48%)
9810.4614
(80.08%)
AUC 0-tau, Month 12 Number Analyzed 12 participants 14 participants 9 participants 11 participants
3922.9369
(75.72%)
6455.1756
(42.03%)
14827.6940
(38.28%)
10079.2847
(71.01%)
21.Secondary Outcome
Title Maximum Blood Concentration (Cmax) of Ronacaleret
Hide Description Blood samples were collected and analyzed for concentrations of ronacaleret. The individual blood concentration-time data from the intensive pharmacokinetic and pharmacodynamics subgroup of participants were analyzed by standard noncompartmental methods. Blood samples were collected and analyzed for concentrations of ronacaleret. The individual blood concentration-time data from the intensive PK-PD subgroup of participants were analyzed by standard noncompartmental methods. Following log transformation, Cmax of ronacaleret were separately analyzed by ANOVA using mixed effects model, fitting treatment and country/region as fixed effects.
Time Frame Pre-dose (0.0 h) and 12 h post dose at Week 4, 20, 40 min, 1, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 1-4, 8-12, and 24 h at Month 3, 6 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic parameter population.
Arm/Group Title Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD
Hide Arm/Group Description:
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 13 14 14 11
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: ng/mL
Cmax. Month 6 Number Analyzed 13 participants 14 participants 14 participants 11 participants
572.10
(44.79%)
1050.42
(40.82%)
1756.45
(52.80%)
1556.58
(76.83%)
Cmax. Month 12 Number Analyzed 12 participants 14 participants 9 participants 11 participants
661.70
(74.39%)
999.91
(37.18%)
2254.26
(41.57%)
1506.45
(63.78%)
22.Secondary Outcome
Title Time Required to Achieve Maximum Concentration of Ronacaleret in Blood (Tmax)
Hide Description Blood samples were collected and analyzed for concentrations of ronacaleret. The individual blood concentration-time data from the intensive pharmacokinetic and pharmacodynamics subgroup of participants were analyzed by standard noncompartmental methods.
Time Frame Pre-dose (0.0 h) and 12 h post dose at Week 4, 20, 40 min, 1, 1.5, 2.0, 2.5, 3.0, 4.0, 6.0, 8.0, 1-4, 8-12, and 24 h at Month 3, 6 and 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic parameters population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD
Hide Arm/Group Description:
Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
Overall Number of Participants Analyzed 13 14 14 11
Median (Full Range)
Unit of Measure: h
Tmax, Month 6 Number Analyzed 13 participants 14 participants 14 participants 11 participants
1.483
(0.98 to 4.02)
1.250
(0.67 to 3.03)
1.700
(0.33 to 3.02)
1.500
(0.67 to 4.07)
Tmax, Month 12 Number Analyzed 12 participants 14 participants 9 participants 11 participants
1.000
(0.33 to 4.00)
1.500
(0.67 to 2.95)
1.500
(0.00 to 2.58)
1.500
(0.33 to 3.00)
Time Frame Up to Follow-up visit (12 month and 2 weeks)
Adverse Event Reporting Description Intent-to-Treat population was used to report AEs
 
Arm/Group Title Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Hide Arm/Group Description Participants received matching placebo OD (matching to ronacaleret tablet) and matching placebo OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 100 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 200 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received ronacaleret, 300 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Ronacaleret, 400 mg tablet, OD and matching placebo, OW (matching to Alendronate capsule) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Alendronate, 70 mg, capsule, OW and matching placebo OD (matching to ronacaleret tablet) for 12 months. Participants were supplied with elemental calcium 500-660 mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study. Participants received Teriparatide, 20 mcg, SC injection, OD for 12 months. Participants were supplied with elemental calcium 500-660mg and vitamin D, at least 400 IU, OD in the evening as dietary supplements throughout the study.
All-Cause Mortality
Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/90 (0.00%)   0/87 (0.00%)   0/82 (0.00%)   0/88 (0.00%)   0/87 (0.00%)   0/89 (0.00%)   0/41 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/90 (0.00%)   2/87 (2.30%)   5/82 (6.10%)   7/88 (7.95%)   3/87 (3.45%)   6/89 (6.74%)   4/41 (9.76%) 
Cardiac disorders               
Acute myocardial infarction  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  1/88 (1.14%)  0/87 (0.00%)  0/89 (0.00%)  0/41 (0.00%) 
Arrhythmia  1  0/90 (0.00%)  1/87 (1.15%)  0/82 (0.00%)  0/88 (0.00%)  0/87 (0.00%)  0/89 (0.00%)  0/41 (0.00%) 
Atrioventricular block  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  1/88 (1.14%)  0/87 (0.00%)  0/89 (0.00%)  0/41 (0.00%) 
Myocardial infarction  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  0/88 (0.00%)  0/87 (0.00%)  1/89 (1.12%)  0/41 (0.00%) 
Gastrointestinal disorders               
Inguinal hernia  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  1/88 (1.14%)  0/87 (0.00%)  0/89 (0.00%)  0/41 (0.00%) 
Upper gastrointestinal haemorrhage  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  0/88 (0.00%)  1/87 (1.15%)  0/89 (0.00%)  0/41 (0.00%) 
General disorders               
Chest pain  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  0/88 (0.00%)  0/87 (0.00%)  0/89 (0.00%)  1/41 (2.44%) 
Hyperplasia  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  0/88 (0.00%)  0/87 (0.00%)  0/89 (0.00%)  1/41 (2.44%) 
Infections and infestations               
Appendicitis  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  0/88 (0.00%)  1/87 (1.15%)  0/89 (0.00%)  0/41 (0.00%) 
Infection  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  0/88 (0.00%)  0/87 (0.00%)  1/89 (1.12%)  0/41 (0.00%) 
Pulmonary tuberculosis  1  0/90 (0.00%)  0/87 (0.00%)  1/82 (1.22%)  0/88 (0.00%)  0/87 (0.00%)  0/89 (0.00%)  0/41 (0.00%) 
Injury, poisoning and procedural complications               
Femoral neck fracture  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  0/88 (0.00%)  0/87 (0.00%)  1/89 (1.12%)  0/41 (0.00%) 
Femur fracture  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  0/88 (0.00%)  0/87 (0.00%)  1/89 (1.12%)  0/41 (0.00%) 
Nerve injury  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  0/88 (0.00%)  0/87 (0.00%)  0/89 (0.00%)  1/41 (2.44%) 
Radius fracture  1  0/90 (0.00%)  1/87 (1.15%)  0/82 (0.00%)  0/88 (0.00%)  0/87 (0.00%)  0/89 (0.00%)  0/41 (0.00%) 
Upper limb fracture  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  0/88 (0.00%)  1/87 (1.15%)  0/89 (0.00%)  0/41 (0.00%) 
Investigations               
Smear cervix abnormal  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  0/88 (0.00%)  0/87 (0.00%)  0/89 (0.00%)  1/41 (2.44%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)               
Metastatic malignant melanoma  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  1/88 (1.14%)  0/87 (0.00%)  0/89 (0.00%)  0/41 (0.00%) 
Neuroma  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  1/88 (1.14%)  0/87 (0.00%)  0/89 (0.00%)  0/41 (0.00%) 
Non-Hodgkin's lymphoma  1  0/90 (0.00%)  0/87 (0.00%)  1/82 (1.22%)  0/88 (0.00%)  0/87 (0.00%)  0/89 (0.00%)  0/41 (0.00%) 
Renal neoplasm  1  0/90 (0.00%)  0/87 (0.00%)  1/82 (1.22%)  0/88 (0.00%)  0/87 (0.00%)  0/89 (0.00%)  0/41 (0.00%) 
Nervous system disorders               
Loss of consciousness  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  1/88 (1.14%)  0/87 (0.00%)  0/89 (0.00%)  0/41 (0.00%) 
Syncope  1  0/90 (0.00%)  0/87 (0.00%)  1/82 (1.22%)  0/88 (0.00%)  0/87 (0.00%)  0/89 (0.00%)  0/41 (0.00%) 
Transient ischaemic attack  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  0/88 (0.00%)  0/87 (0.00%)  0/89 (0.00%)  1/41 (2.44%) 
Reproductive system and breast disorders               
Cystocele  1  0/90 (0.00%)  0/87 (0.00%)  1/82 (1.22%)  0/88 (0.00%)  0/87 (0.00%)  0/89 (0.00%)  0/41 (0.00%) 
Ovarian cyst  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  0/88 (0.00%)  0/87 (0.00%)  1/89 (1.12%)  0/41 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Nasal septum deviation  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  0/88 (0.00%)  0/87 (0.00%)  0/89 (0.00%)  1/41 (2.44%) 
Surgical and medical procedures               
Salpingo-oophorectomy  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  0/88 (0.00%)  0/87 (0.00%)  1/89 (1.12%)  0/41 (0.00%) 
Vascular disorders               
Hypertension  1  0/90 (0.00%)  0/87 (0.00%)  0/82 (0.00%)  1/88 (1.14%)  0/87 (0.00%)  0/89 (0.00%)  0/41 (0.00%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Ronacaleret, 100 mg Tablet, OD Ronacaleret, 200 mg Tablet, OD Ronacaleret, 300 mg Tablet, OD Ronacaleret, 400 mg Tablet, OD Alendronate, 70 mg, Capsule, OW Teriparatide, 20 mcg, SC Injection, OD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   54/90 (60.00%)   54/87 (62.07%)   57/82 (69.51%)   55/88 (62.50%)   61/87 (70.11%)   46/89 (51.69%)   30/41 (73.17%) 
Cardiac disorders               
Palpitations  1  1/90 (1.11%)  1/87 (1.15%)  0/82 (0.00%)  4/88 (4.55%)  2/87 (2.30%)  1/89 (1.12%)  3/41 (7.32%) 
Gastrointestinal disorders               
Diarrhoea  1  5/90 (5.56%)  6/87 (6.90%)  8/82 (9.76%)  11/88 (12.50%)  12/87 (13.79%)  5/89 (5.62%)  1/41 (2.44%) 
Nausea  1  4/90 (4.44%)  1/87 (1.15%)  6/82 (7.32%)  9/88 (10.23%)  11/87 (12.64%)  6/89 (6.74%)  2/41 (4.88%) 
Dyspepsia  1  4/90 (4.44%)  6/87 (6.90%)  3/82 (3.66%)  6/88 (6.82%)  3/87 (3.45%)  4/89 (4.49%)  3/41 (7.32%) 
Constipation  1  2/90 (2.22%)  5/87 (5.75%)  4/82 (4.88%)  9/88 (10.23%)  5/87 (5.75%)  2/89 (2.25%)  0/41 (0.00%) 
Abdominal pain upper  1  6/90 (6.67%)  3/87 (3.45%)  6/82 (7.32%)  4/88 (4.55%)  1/87 (1.15%)  1/89 (1.12%)  0/41 (0.00%) 
Abdominal pain  1  0/90 (0.00%)  5/87 (5.75%)  0/82 (0.00%)  3/88 (3.41%)  2/87 (2.30%)  1/89 (1.12%)  0/41 (0.00%) 
Infections and infestations               
Nasopharyngitis  1  17/90 (18.89%)  16/87 (18.39%)  13/82 (15.85%)  12/88 (13.64%)  16/87 (18.39%)  12/89 (13.48%)  7/41 (17.07%) 
Influenza  1  7/90 (7.78%)  6/87 (6.90%)  5/82 (6.10%)  6/88 (6.82%)  9/87 (10.34%)  7/89 (7.87%)  4/41 (9.76%) 
Upper respiratory tract infection  1  5/90 (5.56%)  5/87 (5.75%)  4/82 (4.88%)  2/88 (2.27%)  8/87 (9.20%)  3/89 (3.37%)  2/41 (4.88%) 
Bronchitis  1  5/90 (5.56%)  4/87 (4.60%)  3/82 (3.66%)  4/88 (4.55%)  1/87 (1.15%)  2/89 (2.25%)  1/41 (2.44%) 
Urinary tract infection  1  3/90 (3.33%)  4/87 (4.60%)  6/82 (7.32%)  0/88 (0.00%)  3/87 (3.45%)  1/89 (1.12%)  2/41 (4.88%) 
Gastroenteritis  1  2/90 (2.22%)  5/87 (5.75%)  0/82 (0.00%)  1/88 (1.14%)  2/87 (2.30%)  2/89 (2.25%)  4/41 (9.76%) 
Tooth infection  1  1/90 (1.11%)  2/87 (2.30%)  0/82 (0.00%)  4/88 (4.55%)  0/87 (0.00%)  2/89 (2.25%)  3/41 (7.32%) 
Injury, poisoning and procedural complications               
Fall  1  1/90 (1.11%)  0/87 (0.00%)  3/82 (3.66%)  2/88 (2.27%)  5/87 (5.75%)  1/89 (1.12%)  0/41 (0.00%) 
Musculoskeletal and connective tissue disorders               
Arthralgia  1  5/90 (5.56%)  7/87 (8.05%)  9/82 (10.98%)  5/88 (5.68%)  10/87 (11.49%)  7/89 (7.87%)  5/41 (12.20%) 
Back pain  1  10/90 (11.11%)  6/87 (6.90%)  2/82 (2.44%)  6/88 (6.82%)  6/87 (6.90%)  5/89 (5.62%)  3/41 (7.32%) 
Pain in extremity  1  3/90 (3.33%)  3/87 (3.45%)  2/82 (2.44%)  0/88 (0.00%)  4/87 (4.60%)  3/89 (3.37%)  4/41 (9.76%) 
Muscle spasms  1  2/90 (2.22%)  5/87 (5.75%)  2/82 (2.44%)  2/88 (2.27%)  1/87 (1.15%)  0/89 (0.00%)  4/41 (9.76%) 
Osteoarthritis  1  3/90 (3.33%)  2/87 (2.30%)  1/82 (1.22%)  1/88 (1.14%)  1/87 (1.15%)  5/89 (5.62%)  0/41 (0.00%) 
Nervous system disorders               
Headache  1  7/90 (7.78%)  5/87 (5.75%)  5/82 (6.10%)  4/88 (4.55%)  4/87 (4.60%)  8/89 (8.99%)  6/41 (14.63%) 
Dizziness  1  4/90 (4.44%)  5/87 (5.75%)  8/82 (9.76%)  5/88 (5.68%)  10/87 (11.49%)  0/89 (0.00%)  6/41 (14.63%) 
Respiratory, thoracic and mediastinal disorders               
Cough  1  5/90 (5.56%)  4/87 (4.60%)  3/82 (3.66%)  2/88 (2.27%)  2/87 (2.30%)  2/89 (2.25%)  0/41 (0.00%) 
Vascular disorders               
Hypertension  1  4/90 (4.44%)  5/87 (5.75%)  5/82 (6.10%)  2/88 (2.27%)  3/87 (3.45%)  3/89 (3.37%)  2/41 (4.88%) 
1
Term from vocabulary, MedDRA
Indicates events were collected by systematic assessment
The study was terminated for futility in a phased manner by the sponsor on 25-Sep-2008 once the results of a planned 6-month interim analysis were available.
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.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00471237     History of Changes
Other Study ID Numbers: CR9108963
First Submitted: May 7, 2007
First Posted: May 9, 2007
Results First Submitted: August 2, 2017
Results First Posted: September 5, 2017
Last Update Posted: November 7, 2017