Trial Outcomes & Findings for A Phase II Study Evaluating SB-751689 in Post-Menopausal Women With Osteoporosis. (NCT NCT00471237)
NCT ID: NCT00471237
Last Updated: 2017-11-07
Results Overview
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.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
564 participants
Primary outcome timeframe
Baseline (Day 0) and 12 Months
Results posted on
2017-11-07
Participant Flow
The study was conducted between 14-May-2007and 26-December-2008 at 45 centres in 14 countries.
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.
Participant milestones
| Measure |
Placebo
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.
|
Ronacaleret, 100 mg Tablet, OD
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.
|
Ronacaleret, 200 mg Tablet, OD
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.
|
Ronacaleret, 300 mg Tablet, OD
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.
|
Ronacaleret, 400 mg Tablet, OD
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.
|
Alendronate, 70 mg, Capsule, OW
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.
|
Teriparatide, 20 mcg, SC Injection, OD
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.
|
|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
90
|
87
|
82
|
88
|
87
|
89
|
41
|
|
Overall Study
COMPLETED
|
49
|
45
|
48
|
43
|
46
|
50
|
38
|
|
Overall Study
NOT COMPLETED
|
41
|
42
|
34
|
45
|
41
|
39
|
3
|
Reasons for withdrawal
| Measure |
Placebo
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.
|
Ronacaleret, 100 mg Tablet, OD
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.
|
Ronacaleret, 200 mg Tablet, OD
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.
|
Ronacaleret, 300 mg Tablet, OD
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.
|
Ronacaleret, 400 mg Tablet, OD
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.
|
Alendronate, 70 mg, Capsule, OW
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.
|
Teriparatide, 20 mcg, SC Injection, OD
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.
|
|---|---|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
6
|
5
|
4
|
8
|
7
|
5
|
0
|
|
Overall Study
Lost to Follow-up
|
1
|
1
|
0
|
2
|
3
|
0
|
0
|
|
Overall Study
Protocol Violation
|
3
|
6
|
3
|
2
|
2
|
4
|
1
|
|
Overall Study
Withdrawal by Subject
|
8
|
6
|
5
|
8
|
7
|
4
|
2
|
|
Overall Study
Sponsor terminated study
|
20
|
23
|
19
|
22
|
18
|
24
|
0
|
|
Overall Study
Non-compliance
|
0
|
1
|
0
|
1
|
0
|
0
|
0
|
|
Overall Study
Met serum creatinine withdrawal criteria
|
1
|
0
|
2
|
2
|
0
|
0
|
0
|
|
Overall Study
Early stopping due to non-efficacy
|
1
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
Participant planned to travel to abraod
|
1
|
0
|
0
|
0
|
0
|
1
|
0
|
|
Overall Study
High parathyroid hormone
|
0
|
0
|
1
|
0
|
0
|
0
|
0
|
|
Overall Study
Participant lost medication
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
Administration of prohibited medicine
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
Participant shifted residence
|
0
|
0
|
0
|
0
|
1
|
0
|
0
|
|
Overall Study
Participant's decision
|
0
|
0
|
0
|
0
|
0
|
1
|
0
|
Baseline Characteristics
A Phase II Study Evaluating SB-751689 in Post-Menopausal Women With Osteoporosis.
Baseline characteristics by cohort
| Measure |
Placebo
n=90 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=87 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=82 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=88 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
n=87 Participants
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.
|
Alendronate, 70 mg, Capsule, OW
n=89 Participants
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.
|
Teriparatide, 20 mcg, SC Injection, OD
n=41 Participants
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
n=564 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|
|
Age, Continuous
|
63.20 Years
STANDARD_DEVIATION 6.75 • n=5 Participants
|
64.17 Years
STANDARD_DEVIATION 7.69 • n=7 Participants
|
64.16 Years
STANDARD_DEVIATION 7.03 • n=5 Participants
|
64.34 Years
STANDARD_DEVIATION 6.57 • n=4 Participants
|
64.97 Years
STANDARD_DEVIATION 7.60 • n=21 Participants
|
65.11 Years
STANDARD_DEVIATION 7.04 • n=10 Participants
|
63.17 Years
STANDARD_DEVIATION 5.92 • n=115 Participants
|
64.24 Years
STANDARD_DEVIATION 7.04 • n=6 Participants
|
|
Sex: Female, Male
Female
|
90 Participants
n=5 Participants
|
87 Participants
n=7 Participants
|
82 Participants
n=5 Participants
|
88 Participants
n=4 Participants
|
87 Participants
n=21 Participants
|
89 Participants
n=10 Participants
|
41 Participants
n=115 Participants
|
564 Participants
n=6 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
0 Participants
n=6 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage
|
1 Participant
n=5 Participants
|
2 Participant
n=7 Participants
|
1 Participant
n=5 Participants
|
0 Participant
n=4 Participants
|
4 Participant
n=21 Participants
|
1 Participant
n=10 Participants
|
0 Participant
n=115 Participants
|
9 Participant
n=6 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
5 Participant
n=5 Participants
|
5 Participant
n=7 Participants
|
3 Participant
n=5 Participants
|
3 Participant
n=4 Participants
|
1 Participant
n=21 Participants
|
4 Participant
n=10 Participants
|
3 Participant
n=115 Participants
|
24 Participant
n=6 Participants
|
|
Race/Ethnicity, Customized
Asian
|
10 Participant
n=5 Participants
|
7 Participant
n=7 Participants
|
10 Participant
n=5 Participants
|
11 Participant
n=4 Participants
|
10 Participant
n=21 Participants
|
8 Participant
n=10 Participants
|
3 Participant
n=115 Participants
|
59 Participant
n=6 Participants
|
|
Race/Ethnicity, Customized
White
|
73 Participant
n=5 Participants
|
71 Participant
n=7 Participants
|
66 Participant
n=5 Participants
|
73 Participant
n=4 Participants
|
71 Participant
n=21 Participants
|
76 Participant
n=10 Participants
|
35 Participant
n=115 Participants
|
465 Participant
n=6 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage & White
|
1 Participant
n=5 Participants
|
2 Participant
n=7 Participants
|
2 Participant
n=5 Participants
|
1 Participant
n=4 Participants
|
1 Participant
n=21 Participants
|
0 Participant
n=10 Participants
|
0 Participant
n=115 Participants
|
7 Participant
n=6 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day 0) and 12 MonthsPopulation: 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.
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.
Outcome measures
| Measure |
Placebo
n=79 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=76 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=74 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=78 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
n=72 Participants
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.
|
Alendronate, 70 mg, Capsule, OW
n=75 Participants
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.
|
Teriparatide, 20 mcg, SC Injection, OD
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.
|
|---|---|---|---|---|---|---|---|
|
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)
|
0.03 Percent change in BMD
Standard Error 0.38
|
0.32 Percent change in BMD
Standard Error 0.40
|
1.39 Percent change in BMD
Standard Error 0.40
|
1.61 Percent change in BMD
Standard Error 0.39
|
1.62 Percent change in BMD
Standard Error 0.40
|
4.54 Percent change in BMD
Standard Error 0.40
|
—
|
PRIMARY outcome
Timeframe: Up to Month 12Population: Intent-to-Treat population.
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.
Outcome measures
| Measure |
Placebo
n=90 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=87 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=82 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=88 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
n=87 Participants
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.
|
Alendronate, 70 mg, Capsule, OW
n=89 Participants
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.
|
Teriparatide, 20 mcg, SC Injection, OD
n=41 Participants
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.
|
|---|---|---|---|---|---|---|---|
|
Number of Participants With Hypercalcemia
|
0 Participants
|
1 Participants
|
1 Participants
|
4 Participants
|
11 Participants
|
0 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: Up to Month 12Population: Intent-to-Treat population.
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.
Outcome measures
| Measure |
Placebo
n=90 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=87 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=82 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=88 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
n=87 Participants
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.
|
Alendronate, 70 mg, Capsule, OW
n=89 Participants
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.
|
Teriparatide, 20 mcg, SC Injection, OD
n=41 Participants
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.
|
|---|---|---|---|---|---|---|---|
|
Number of Participants Withdrew Due to Hypercalcemia
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to Month 12Population: Intent-to-Treat population.
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.
Outcome measures
| Measure |
Placebo
n=90 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=87 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=82 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=88 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
n=87 Participants
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.
|
Alendronate, 70 mg, Capsule, OW
n=89 Participants
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.
|
Teriparatide, 20 mcg, SC Injection, OD
n=41 Participants
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.
|
|---|---|---|---|---|---|---|---|
|
Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
Alkaline Phosphatase- high
|
0 Participants
|
1 Participants
|
0 Participants
|
3 Participants
|
3 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
Monocytes- high
|
17 Participants
|
14 Participants
|
19 Participants
|
17 Participants
|
18 Participants
|
28 Participants
|
6 Participants
|
|
Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
Total neutrophils- high
|
9 Participants
|
11 Participants
|
10 Participants
|
10 Participants
|
4 Participants
|
6 Participants
|
4 Participants
|
|
Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
Total neutrophils- low
|
16 Participants
|
5 Participants
|
8 Participants
|
8 Participants
|
14 Participants
|
13 Participants
|
4 Participants
|
|
Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
Eosinophils- high
|
12 Participants
|
8 Participants
|
11 Participants
|
18 Participants
|
19 Participants
|
11 Participants
|
6 Participants
|
|
Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
Glucose- high
|
10 Participants
|
6 Participants
|
9 Participants
|
5 Participants
|
4 Participants
|
5 Participants
|
3 Participants
|
|
Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
Glucose- low
|
3 Participants
|
0 Participants
|
4 Participants
|
0 Participants
|
3 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
Basophils- high
|
2 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
Hematocrit- low
|
2 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
Hemoglobin- high
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
Hemoglobin- low
|
2 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
Platelets- high
|
2 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
White Blood Cell- high
|
1 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
White Blood Cell- low
|
1 Participants
|
1 Participants
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
Calcium- high
|
0 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
Phosphorus- high
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participant With Laboratory Abnormalities of Potential Clinical Concern at Any Post-baseline Visit
Total bilirubin- high
|
0 Participants
|
1 Participants
|
2 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to 12 MonthsPopulation: Intent-to-Treat population.
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.
Outcome measures
| Measure |
Placebo
n=90 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=87 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=82 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=88 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
n=87 Participants
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.
|
Alendronate, 70 mg, Capsule, OW
n=89 Participants
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.
|
Teriparatide, 20 mcg, SC Injection, OD
n=41 Participants
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.
|
|---|---|---|---|---|---|---|---|
|
Number of Participant With Vital Signs of Potential Clinical Concern at Any Post-baseline Visit
Systolic Blood Pressure, Low
|
6 Participants
|
8 Participants
|
10 Participants
|
6 Participants
|
4 Participants
|
8 Participants
|
3 Participants
|
|
Number of Participant With Vital Signs of Potential Clinical Concern at Any Post-baseline Visit
Diastolic Blood Pressure, High
|
2 Participants
|
6 Participants
|
5 Participants
|
1 Participants
|
6 Participants
|
3 Participants
|
1 Participants
|
|
Number of Participant With Vital Signs of Potential Clinical Concern at Any Post-baseline Visit
Systolic Blood Pressure, High
|
5 Participants
|
10 Participants
|
8 Participants
|
9 Participants
|
11 Participants
|
8 Participants
|
1 Participants
|
|
Number of Participant With Vital Signs of Potential Clinical Concern at Any Post-baseline Visit
Diastolic Blood Pressure, Low
|
8 Participants
|
9 Participants
|
4 Participants
|
12 Participants
|
10 Participants
|
10 Participants
|
2 Participants
|
|
Number of Participant With Vital Signs of Potential Clinical Concern at Any Post-baseline Visit
Heart Rate, Low
|
2 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Up to 12 monthsPopulation: Intent-to-Treat population.
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.
Outcome measures
| Measure |
Placebo
n=90 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=87 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=82 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=88 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
n=87 Participants
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.
|
Alendronate, 70 mg, Capsule, OW
n=89 Participants
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.
|
Teriparatide, 20 mcg, SC Injection, OD
n=41 Participants
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.
|
|---|---|---|---|---|---|---|---|
|
Number of Participant With Electrocardiogram (ECG) Findings Reported as Adverse Event
|
1 Participants
|
5 Participants
|
4 Participants
|
3 Participants
|
3 Participants
|
5 Participants
|
0 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day 0), Month 6, 12 and early withdrawalPopulation: Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Placebo
n=90 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=87 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=82 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=88 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
n=87 Participants
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.
|
Alendronate, 70 mg, Capsule, OW
n=89 Participants
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.
|
Teriparatide, 20 mcg, SC Injection, OD
n=41 Participants
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.
|
|---|---|---|---|---|---|---|---|
|
Mean Change From Baseline in Height
Month 6
|
-0.04 Centimeter
Standard Deviation 0.58
|
0.17 Centimeter
Standard Deviation 1.41
|
0.72 Centimeter
Standard Deviation 3.82
|
0.05 Centimeter
Standard Deviation 0.70
|
-0.04 Centimeter
Standard Deviation 0.82
|
-0.07 Centimeter
Standard Deviation 1.13
|
0.11 Centimeter
Standard Deviation 0.65
|
|
Mean Change From Baseline in Height
Month 12
|
-0.14 Centimeter
Standard Deviation 0.65
|
0.04 Centimeter
Standard Deviation 1.59
|
0.02 Centimeter
Standard Deviation 0.76
|
-0.09 Centimeter
Standard Deviation 1.04
|
-0.17 Centimeter
Standard Deviation 0.67
|
-0.08 Centimeter
Standard Deviation 0.57
|
0.11 Centimeter
Standard Deviation 0.56
|
|
Mean Change From Baseline in Height
Early withdrawal
|
0.03 Centimeter
Standard Deviation 0.61
|
0.17 Centimeter
Standard Deviation 1.92
|
-0.13 Centimeter
Standard Deviation 0.55
|
-0.16 Centimeter
Standard Deviation 0.76
|
-0.16 Centimeter
Standard Deviation 0.82
|
-0.37 Centimeter
Standard Deviation 0.88
|
0 Centimeter
Standard Deviation 0
|
PRIMARY outcome
Timeframe: Baseline (Day 0), Month 6, 12 and early withdrawalPopulation: Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Placebo
n=90 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=87 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=82 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=88 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
n=87 Participants
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.
|
Alendronate, 70 mg, Capsule, OW
n=89 Participants
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.
|
Teriparatide, 20 mcg, SC Injection, OD
n=41 Participants
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.
|
|---|---|---|---|---|---|---|---|
|
Mean Change From Baseline in Weight
Month 6
|
-0.02 Kilogram
Standard Deviation 2.12
|
0.27 Kilogram
Standard Deviation 3.27
|
0.45 Kilogram
Standard Deviation 2.98
|
-0.24 Kilogram
Standard Deviation 2.87
|
0.11 Kilogram
Standard Deviation 2.84
|
0.29 Kilogram
Standard Deviation 1.89
|
0.51 Kilogram
Standard Deviation 1.84
|
|
Mean Change From Baseline in Weight
Month 12
|
0.32 Kilogram
Standard Deviation 2.73
|
-0.72 Kilogram
Standard Deviation 2.70
|
1.18 Kilogram
Standard Deviation 9.78
|
-0.22 Kilogram
Standard Deviation 2.36
|
-0.48 Kilogram
Standard Deviation 2.28
|
0.57 Kilogram
Standard Deviation 3.22
|
0.09 Kilogram
Standard Deviation 2.45
|
|
Mean Change From Baseline in Weight
Early withdrawal
|
-0.45 Kilogram
Standard Deviation 2.40
|
0.40 Kilogram
Standard Deviation 4.60
|
-0.34 Kilogram
Standard Deviation 2.48
|
0.37 Kilogram
Standard Deviation 3.86
|
0.00 Kilogram
Standard Deviation 2.17
|
-0.12 Kilogram
Standard Deviation 2.33
|
-2.15 Kilogram
Standard Deviation 1.48
|
SECONDARY outcome
Timeframe: Baseline (Day 0) and Month 6Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=79 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=76 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=74 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=77 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
n=73 Participants
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.
|
Alendronate, 70 mg, Capsule, OW
n=75 Participants
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.
|
Teriparatide, 20 mcg, SC Injection, OD
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.
|
|---|---|---|---|---|---|---|---|
|
Percent Change From Baseline to Month 6 in BMD Measured by DXA Scans of the Lumbar Spine (L1-L4)
|
0.66 percent change in BMD
Standard Error 0.33
|
0.21 percent change in BMD
Standard Error 0.34
|
1.61 percent change in BMD
Standard Error 0.35
|
0.47 percent change in BMD
Standard Error 0.34
|
1.01 percent change in BMD
Standard Error 0.35
|
3.42 percent change in BMD
Standard Error 0.34
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 0), Month 6 and Month 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=90 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=87 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=82 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=88 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
n=87 Participants
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.
|
Alendronate, 70 mg, Capsule, OW
n=89 Participants
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.
|
Teriparatide, 20 mcg, SC Injection, OD
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.
|
|---|---|---|---|---|---|---|---|
|
Percent Change From Baseline to Months 6 and 12 in BMD Measured by DXA Scans of the Hip (Total Hip, Femoral Neck and Trochanter).
Total Hip aBMD, Month 6
|
0.42 Percent change in BMD
Standard Error 0.23
|
-0.26 Percent change in BMD
Standard Error 0.24
|
-0.37 Percent change in BMD
Standard Error 0.24
|
-0.86 Percent change in BMD
Standard Error 0.23
|
-0.88 Percent change in BMD
Standard Error 0.24
|
1.84 Percent change in BMD
Standard Error 0.24
|
—
|
|
Percent Change From Baseline to Months 6 and 12 in BMD Measured by DXA Scans of the Hip (Total Hip, Femoral Neck and Trochanter).
Total Hip aBMD, Month 12
|
0.27 Percent change in BMD
Standard Error 0.26
|
-0.62 Percent change in BMD
Standard Error 0.26
|
-0.75 Percent change in BMD
Standard Error 0.27
|
-1.07 Percent change in BMD
Standard Error 0.26
|
-1.31 Percent change in BMD
Standard Error 0.27
|
2.70 Percent change in BMD
Standard Error 0.27
|
—
|
SECONDARY outcome
Timeframe: Baseline (Day 0), Month 5, 6 and 12Population: Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
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%.
Outcome measures
| Measure |
Placebo
n=90 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=87 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=82 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=88 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
n=87 Participants
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.
|
Alendronate, 70 mg, Capsule, OW
n=89 Participants
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.
|
Teriparatide, 20 mcg, SC Injection, OD
n=41 Participants
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.
|
|---|---|---|---|---|---|---|---|
|
Number of Participants Who Remained the Same or Had Any Improvement in DXA BMD (> Baseline)
Month 6, Vertebra, BMD % change >=0
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants Who Remained the Same or Had Any Improvement in DXA BMD (> Baseline)
Month 6, Femur, BMD % change >=0
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants Who Remained the Same or Had Any Improvement in DXA BMD (> Baseline)
Early Withdrawal, Vertebra + Femur, BMD %change>=0
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants Who Remained the Same or Had Any Improvement in DXA BMD (> Baseline)
Month 5, Vertebra, BMD % change >=0
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Who Remained the Same or Had Any Improvement in DXA BMD (> Baseline)
Month 5, Femur, BMD % change >=0
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Who Remained the Same or Had Any Improvement in DXA BMD (> Baseline)
Month 5, Vertebra + Femur, BMD % change >=0
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants Who Remained the Same or Had Any Improvement in DXA BMD (> Baseline)
Month 6, Vertebra + Femur, BMD % change >=0
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
0 Participants
|
|
Number of Participants Who Remained the Same or Had Any Improvement in DXA BMD (> Baseline)
Month 12, Vertebra, BMD % change >=0
|
16 Participants
|
29 Participants
|
32 Participants
|
35 Participants
|
31 Participants
|
44 Participants
|
34 Participants
|
|
Number of Participants Who Remained the Same or Had Any Improvement in DXA BMD (> Baseline)
Month 12, Femur, BMD % change >=0
|
20 Participants
|
23 Participants
|
14 Participants
|
19 Participants
|
16 Participants
|
40 Participants
|
25 Participants
|
|
Number of Participants Who Remained the Same or Had Any Improvement in DXA BMD (> Baseline)
Month 12, Vertebra + Femur, BMD % change >=0
|
10 Participants
|
19 Participants
|
12 Participants
|
17 Participants
|
16 Participants
|
35 Participants
|
24 Participants
|
|
Number of Participants Who Remained the Same or Had Any Improvement in DXA BMD (> Baseline)
Early Withdrawal, Vertebra, BMD % change >=0
|
1 Participants
|
1 Participants
|
1 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Number of Participants Who Remained the Same or Had Any Improvement in DXA BMD (> Baseline)
Early Withdrawal, Femur, BMD % change >=0
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: Baseline (Day 0) and Month 12Population: Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Placebo
n=90 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=87 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=82 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=88 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
n=87 Participants
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.
|
Alendronate, 70 mg, Capsule, OW
n=89 Participants
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.
|
Teriparatide, 20 mcg, SC Injection, OD
n=41 Participants
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.
|
|---|---|---|---|---|---|---|---|
|
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
Mid Osteo cortical VOI BMD
|
-0.30 Percent change in BMD
Standard Deviation 4.69
|
0.63 Percent change in BMD
Standard Deviation 4.80
|
2.37 Percent change in BMD
Standard Deviation 6.37
|
2.57 Percent change in BMD
Standard Deviation 5.14
|
1.22 Percent change in BMD
Standard Deviation 4.39
|
4.98 Percent change in BMD
Standard Deviation 4.63
|
9.25 Percent change in BMD
Standard Deviation 7.68
|
|
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
Total vertebra integral VOI BMD
|
-0.98 Percent change in BMD
Standard Deviation 3.13
|
1.09 Percent change in BMD
Standard Deviation 4.01
|
3.00 Percent change in BMD
Standard Deviation 4.98
|
3.91 Percent change in BMD
Standard Deviation 4.98
|
4.83 Percent change in BMD
Standard Deviation 6.56
|
5.04 Percent change in BMD
Standard Deviation 4.39
|
14.80 Percent change in BMD
Standard Deviation 8.69
|
|
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
Mid vertebra integral VOI BMD
|
-1.31 Percent change in BMD
Standard Deviation 3.54
|
1.20 Percent change in BMD
Standard Deviation 4.85
|
4.65 Percent change in BMD
Standard Deviation 5.87
|
6.06 Percent change in BMD
Standard Deviation 6.48
|
7.33 Percent change in BMD
Standard Deviation 8.67
|
4.85 Percent change in BMD
Standard Deviation 5.25
|
17.97 Percent change in BMD
Standard Deviation 11.27
|
|
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
Mid Cylinder trabecular VOI BMD
|
-2.45 Percent change in BMD
Standard Deviation 4.39
|
1.75 Percent change in BMD
Standard Deviation 8.70
|
6.17 Percent change in BMD
Standard Deviation 10.37
|
8.99 Percent change in BMD
Standard Deviation 10.52
|
13.29 Percent change in BMD
Standard Deviation 15.32
|
4.88 Percent change in BMD
Standard Deviation 7.68
|
24.37 Percent change in BMD
Standard Deviation 15.92
|
|
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
Mid Osteo trabecular VOI BMD
|
-2.21 Percent change in BMD
Standard Deviation 4.58
|
1.81 Percent change in BMD
Standard Deviation 8.26
|
7.06 Percent change in BMD
Standard Deviation 9.25
|
9.54 Percent change in BMD
Standard Deviation 9.79
|
13.21 Percent change in BMD
Standard Deviation 14.68
|
5.15 Percent change in BMD
Standard Deviation 6.86
|
24.21 Percent change in BMD
Standard Deviation 15.80
|
|
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
Total vertebra trabecular VOI BMD
|
-2.46 Percent change in BMD
Standard Deviation 4.58
|
1.67 Percent change in BMD
Standard Deviation 7.18
|
5.81 Percent change in BMD
Standard Deviation 8.31
|
8.52 Percent change in BMD
Standard Deviation 8.97
|
11.40 Percent change in BMD
Standard Deviation 12.83
|
4.97 Percent change in BMD
Standard Deviation 6.43
|
23.82 Percent change in BMD
Standard Deviation 14.64
|
SECONDARY outcome
Timeframe: Baseline (Day 0) and Month 12Population: Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
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%.
Outcome measures
| Measure |
Placebo
n=42 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=50 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=43 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=43 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
n=41 Participants
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.
|
Alendronate, 70 mg, Capsule, OW
n=49 Participants
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.
|
Teriparatide, 20 mcg, SC Injection, OD
n=36 Participants
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.
|
|---|---|---|---|---|---|---|---|
|
Percent Change From Baseline to Month 12 in the Total Vertebra Integral VOI at the Lumbar Spine as Measured by QCT Scans
|
0.04 Percent change in VOI
Standard Deviation 4.19
|
0.85 Percent change in VOI
Standard Deviation 4.14
|
3.01 Percent change in VOI
Standard Deviation 5.18
|
3.58 Percent change in VOI
Standard Deviation 5.70
|
3.54 Percent change in VOI
Standard Deviation 5.64
|
5.39 Percent change in VOI
Standard Deviation 5.87
|
12.23 Percent change in VOI
Standard Deviation 8.43
|
SECONDARY outcome
Timeframe: Baseline (Day 0) and Month 12Population: Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
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%.
Outcome measures
| Measure |
Placebo
n=41 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=47 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=40 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=39 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
n=37 Participants
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.
|
Alendronate, 70 mg, Capsule, OW
n=45 Participants
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.
|
Teriparatide, 20 mcg, SC Injection, OD
n=26 Participants
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.
|
|---|---|---|---|---|---|---|---|
|
Percent Change From Baseline to Month 12 in the Volumetric Integral, Cortical, and Trabecular Density (BMD) at the Hip as Measured by QCT Scans
Femur integral VOI BMD
|
0.02 Percent change in BMD
Standard Deviation 2.78
|
-0.05 Percent change in BMD
Standard Deviation 2.67
|
-0.81 Percent change in BMD
Standard Deviation 2.80
|
-0.53 Percent change in BMD
Standard Deviation 2.18
|
-0.15 Percent change in BMD
Standard Deviation 2.98
|
2.70 Percent change in BMD
Standard Deviation 2.13
|
3.92 Percent change in BMD
Standard Deviation 2.67
|
|
Percent Change From Baseline to Month 12 in the Volumetric Integral, Cortical, and Trabecular Density (BMD) at the Hip as Measured by QCT Scans
Femur trabecular VOI BMD
|
-0.36 Percent change in BMD
Standard Deviation 5.53
|
-0.40 Percent change in BMD
Standard Deviation 6.81
|
-2.16 Percent change in BMD
Standard Deviation 7.39
|
1.16 Percent change in BMD
Standard Deviation 5.06
|
2.81 Percent change in BMD
Standard Deviation 8.20
|
3.05 Percent change in BMD
Standard Deviation 5.92
|
13.19 Percent change in BMD
Standard Deviation 8.96
|
|
Percent Change From Baseline to Month 12 in the Volumetric Integral, Cortical, and Trabecular Density (BMD) at the Hip as Measured by QCT Scans
Neck trabecular VOI BMD
|
-0.95 Percent change in BMD
Standard Deviation 7.44
|
-2.19 Percent change in BMD
Standard Deviation 7.91
|
-2.68 Percent change in BMD
Standard Deviation 6.14
|
1.35 Percent change in BMD
Standard Deviation 9.91
|
3.05 Percent change in BMD
Standard Deviation 11.18
|
2.77 Percent change in BMD
Standard Deviation 7.55
|
11.27 Percent change in BMD
Standard Deviation 10.31
|
|
Percent Change From Baseline to Month 12 in the Volumetric Integral, Cortical, and Trabecular Density (BMD) at the Hip as Measured by QCT Scans
Trochanter integral VOI BMD
|
-0.58 Percent change in BMD
Standard Deviation 3.88
|
-0.16 Percent change in BMD
Standard Deviation 4.22
|
-1.53 Percent change in BMD
Standard Deviation 3.92
|
-1.16 Percent change in BMD
Standard Deviation 3.29
|
-0.98 Percent change in BMD
Standard Deviation 3.83
|
3.15 Percent change in BMD
Standard Deviation 3.27
|
4.96 Percent change in BMD
Standard Deviation 4.74
|
|
Percent Change From Baseline to Month 12 in the Volumetric Integral, Cortical, and Trabecular Density (BMD) at the Hip as Measured by QCT Scans
Femur cortical VOI BMD
|
1.11 Percent change in BMD
Standard Deviation 4.04
|
-0.32 Percent change in BMD
Standard Deviation 2.90
|
-1.46 Percent change in BMD
Standard Deviation 2.81
|
-1.06 Percent change in BMD
Standard Deviation 2.53
|
-1.79 Percent change in BMD
Standard Deviation 3.01
|
2.44 Percent change in BMD
Standard Deviation 3.13
|
0.22 Percent change in BMD
Standard Deviation 2.63
|
|
Percent Change From Baseline to Month 12 in the Volumetric Integral, Cortical, and Trabecular Density (BMD) at the Hip as Measured by QCT Scans
Neck integral VOI BMD
|
-0.10 Percent change in BMD
Standard Deviation 2.48
|
0.16 Percent change in BMD
Standard Deviation 2.83
|
-0.94 Percent change in BMD
Standard Deviation 3.34
|
-1.20 Percent change in BMD
Standard Deviation 2.99
|
-1.45 Percent change in BMD
Standard Deviation 3.22
|
1.65 Percent change in BMD
Standard Deviation 2.72
|
2.06 Percent change in BMD
Standard Deviation 3.65
|
|
Percent Change From Baseline to Month 12 in the Volumetric Integral, Cortical, and Trabecular Density (BMD) at the Hip as Measured by QCT Scans
Neck cortical VOI BMD
|
1.23 Percent change in BMD
Standard Deviation 4.55
|
0.44 Percent change in BMD
Standard Deviation 4.16
|
-1.67 Percent change in BMD
Standard Deviation 3.95
|
-1.85 Percent change in BMD
Standard Deviation 3.89
|
-2.80 Percent change in BMD
Standard Deviation 4.55
|
1.10 Percent change in BMD
Standard Deviation 4.25
|
-0.69 Percent change in BMD
Standard Deviation 4.49
|
|
Percent Change From Baseline to Month 12 in the Volumetric Integral, Cortical, and Trabecular Density (BMD) at the Hip as Measured by QCT Scans
Trochanter trabecular VOI BMD
|
-1.62 Percent change in BMD
Standard Deviation 9.67
|
-1.34 Percent change in BMD
Standard Deviation 13.50
|
-2.54 Percent change in BMD
Standard Deviation 11.05
|
2.12 Percent change in BMD
Standard Deviation 8.82
|
2.10 Percent change in BMD
Standard Deviation 10.66
|
3.55 Percent change in BMD
Standard Deviation 7.55
|
14.12 Percent change in BMD
Standard Deviation 14.51
|
|
Percent Change From Baseline to Month 12 in the Volumetric Integral, Cortical, and Trabecular Density (BMD) at the Hip as Measured by QCT Scans
Trochanter cortical VOI BMD
|
0.56 Percent change in BMD
Standard Deviation 5.29
|
-0.70 Percent change in BMD
Standard Deviation 4.08
|
-1.53 Percent change in BMD
Standard Deviation 3.60
|
-1.48 Percent change in BMD
Standard Deviation 3.53
|
-2.59 Percent change in BMD
Standard Deviation 4.04
|
3.33 Percent change in BMD
Standard Deviation 3.57
|
1.99 Percent change in BMD
Standard Deviation 4.37
|
SECONDARY outcome
Timeframe: Baseline (Day 0) and Month 12Population: Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
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%.
Outcome measures
| Measure |
Placebo
n=41 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=47 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=40 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=39 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
n=37 Participants
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.
|
Alendronate, 70 mg, Capsule, OW
n=45 Participants
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.
|
Teriparatide, 20 mcg, SC Injection, OD
n=26 Participants
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.
|
|---|---|---|---|---|---|---|---|
|
Percent Change From Baseline to Month 12 in Cortical Thickness at the Hip as Measured by QCT Scans
Neck cortical VOI Thickness
|
-0.85 Percent change in cortical thickness
Standard Deviation 7.09
|
-0.13 Percent change in cortical thickness
Standard Deviation 5.98
|
1.12 Percent change in cortical thickness
Standard Deviation 5.75
|
-0.88 Percent change in cortical thickness
Standard Deviation 4.73
|
0.32 Percent change in cortical thickness
Standard Deviation 4.93
|
-0.13 Percent change in cortical thickness
Standard Deviation 5.98
|
0.39 Percent change in cortical thickness
Standard Deviation 4.36
|
|
Percent Change From Baseline to Month 12 in Cortical Thickness at the Hip as Measured by QCT Scans
Trochanter cortical VOI Thickness
|
-1.00 Percent change in cortical thickness
Standard Deviation 5.85
|
0.76 Percent change in cortical thickness
Standard Deviation 4.40
|
1.01 Percent change in cortical thickness
Standard Deviation 5.15
|
-0.82 Percent change in cortical thickness
Standard Deviation 3.65
|
1.60 Percent change in cortical thickness
Standard Deviation 3.70
|
0.81 Percent change in cortical thickness
Standard Deviation 5.39
|
0.76 Percent change in cortical thickness
Standard Deviation 2.93
|
SECONDARY outcome
Timeframe: Baseline (Day 0), Week 4, Month 3, 6, and 12Population: Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
Blood samples were collected at Baseline (Day 0), Week 4, Month 3, 6, and 12 for measurement of CTX1.
Outcome measures
| Measure |
Placebo
n=90 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=87 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=82 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=88 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
n=87 Participants
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.
|
Alendronate, 70 mg, Capsule, OW
n=89 Participants
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.
|
Teriparatide, 20 mcg, SC Injection, OD
n=41 Participants
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.
|
|---|---|---|---|---|---|---|---|
|
Biochemical Markers of Bone Turnover: Levels of C-terminal Telopeptide α1 Chain of Type 1 Collagen (CTX1)
Week 4
|
530.7 nanogram per litre (ng/L)
Standard Error 1.05
|
515.2 nanogram per litre (ng/L)
Standard Error 1.05
|
525.4 nanogram per litre (ng/L)
Standard Error 1.05
|
506.1 nanogram per litre (ng/L)
Standard Error 1.05
|
529.2 nanogram per litre (ng/L)
Standard Error 1.05
|
288.0 nanogram per litre (ng/L)
Standard Error 1.06
|
576.1 nanogram per litre (ng/L)
Standard Error 1.08
|
|
Biochemical Markers of Bone Turnover: Levels of C-terminal Telopeptide α1 Chain of Type 1 Collagen (CTX1)
Week 4, Placebo contrast
|
—
|
0.97 nanogram per litre (ng/L)
Standard Error 1.08
|
0.99 nanogram per litre (ng/L)
Standard Error 1.08
|
0.95 nanogram per litre (ng/L)
Standard Error 1.08
|
1.00 nanogram per litre (ng/L)
Standard Error 1.08
|
0.54 nanogram per litre (ng/L)
Standard Error 1.08
|
1.09 nanogram per litre (ng/L)
Standard Error 1.10
|
|
Biochemical Markers of Bone Turnover: Levels of C-terminal Telopeptide α1 Chain of Type 1 Collagen (CTX1)
Baseline
|
625.2 nanogram per litre (ng/L)
Standard Error 1.05
|
635.3 nanogram per litre (ng/L)
Standard Error 1.05
|
632.0 nanogram per litre (ng/L)
Standard Error 1.05
|
587.9 nanogram per litre (ng/L)
Standard Error 1.05
|
645.5 nanogram per litre (ng/L)
Standard Error 1.05
|
630.4 nanogram per litre (ng/L)
Standard Error 1.05
|
564.0 nanogram per litre (ng/L)
Standard Error 1.07
|
|
Biochemical Markers of Bone Turnover: Levels of C-terminal Telopeptide α1 Chain of Type 1 Collagen (CTX1)
Baseline, Placebo contrast
|
—
|
1.02 nanogram per litre (ng/L)
Standard Error 1.07
|
1.01 nanogram per litre (ng/L)
Standard Error 1.07
|
0.94 nanogram per litre (ng/L)
Standard Error 1.07
|
1.03 nanogram per litre (ng/L)
Standard Error 1.07
|
1.01 nanogram per litre (ng/L)
Standard Error 1.07
|
0.90 nanogram per litre (ng/L)
Standard Error 1.09
|
|
Biochemical Markers of Bone Turnover: Levels of C-terminal Telopeptide α1 Chain of Type 1 Collagen (CTX1)
Month 3
|
523.5 nanogram per litre (ng/L)
Standard Error 1.05
|
598.5 nanogram per litre (ng/L)
Standard Error 1.06
|
688.9 nanogram per litre (ng/L)
Standard Error 1.06
|
723.2 nanogram per litre (ng/L)
Standard Error 1.05
|
818.9 nanogram per litre (ng/L)
Standard Error 1.06
|
257.1 nanogram per litre (ng/L)
Standard Error 1.06
|
864.1 nanogram per litre (ng/L)
Standard Error 1.08
|
|
Biochemical Markers of Bone Turnover: Levels of C-terminal Telopeptide α1 Chain of Type 1 Collagen (CTX1)
Month 3, Placebo contrast
|
—
|
1.14 nanogram per litre (ng/L)
Standard Error 1.08
|
1.32 nanogram per litre (ng/L)
Standard Error 1.08
|
1.38 nanogram per litre (ng/L)
Standard Error 1.08
|
1.56 nanogram per litre (ng/L)
Standard Error 1.08
|
0.49 nanogram per litre (ng/L)
Standard Error 1.08
|
1.65 nanogram per litre (ng/L)
Standard Error 1.10
|
|
Biochemical Markers of Bone Turnover: Levels of C-terminal Telopeptide α1 Chain of Type 1 Collagen (CTX1)
Month 6
|
517.6 nanogram per litre (ng/L)
Standard Error 1.06
|
648.2 nanogram per litre (ng/L)
Standard Error 1.06
|
777.1 nanogram per litre (ng/L)
Standard Error 1.06
|
859.6 nanogram per litre (ng/L)
Standard Error 1.06
|
964.3 nanogram per litre (ng/L)
Standard Error 1.06
|
235.9 nanogram per litre (ng/L)
Standard Error 1.07
|
1112 nanogram per litre (ng/L)
Standard Error 1.08
|
|
Biochemical Markers of Bone Turnover: Levels of C-terminal Telopeptide α1 Chain of Type 1 Collagen (CTX1)
Month 6, Placebo contrast
|
—
|
1.25 nanogram per litre (ng/L)
Standard Error 1.08
|
1.50 nanogram per litre (ng/L)
Standard Error 1.08
|
1.66 nanogram per litre (ng/L)
Standard Error 1.08
|
1.86 nanogram per litre (ng/L)
Standard Error 1.08
|
0.46 nanogram per litre (ng/L)
Standard Error 1.09
|
2.15 nanogram per litre (ng/L)
Standard Error 1.10
|
|
Biochemical Markers of Bone Turnover: Levels of C-terminal Telopeptide α1 Chain of Type 1 Collagen (CTX1)
Month 12
|
525.1 nanogram per litre (ng/L)
Standard Error 1.08
|
695.2 nanogram per litre (ng/L)
Standard Error 1.08
|
806.1 nanogram per litre (ng/L)
Standard Error 1.08
|
852.8 nanogram per litre (ng/L)
Standard Error 1.08
|
991.9 nanogram per litre (ng/L)
Standard Error 1.08
|
158.3 nanogram per litre (ng/L)
Standard Error 1.08
|
1071 nanogram per litre (ng/L)
Standard Error 1.10
|
|
Biochemical Markers of Bone Turnover: Levels of C-terminal Telopeptide α1 Chain of Type 1 Collagen (CTX1)
Month 12, Placebo contrast
|
—
|
1.32 nanogram per litre (ng/L)
Standard Error 1.12
|
1.54 nanogram per litre (ng/L)
Standard Error 1.11
|
1.62 nanogram per litre (ng/L)
Standard Error 1.12
|
1.89 nanogram per litre (ng/L)
Standard Error 1.11
|
0.30 nanogram per litre (ng/L)
Standard Error 1.11
|
2.04 nanogram per litre (ng/L)
Standard Error 1.13
|
SECONDARY outcome
Timeframe: Baseline (Day 0), Week 4, Month 3, 6, and 12Population: Intent to treat population. Only those participants available at the specified time points were analyzed.
Blood samples were collected at Baseline (Day 0), Week 4, Month 3, 6, and 12 for measurement of P1NP.
Outcome measures
| Measure |
Placebo
n=90 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=87 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=82 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=88 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
n=87 Participants
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.
|
Alendronate, 70 mg, Capsule, OW
n=89 Participants
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.
|
Teriparatide, 20 mcg, SC Injection, OD
n=41 Participants
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.
|
|---|---|---|---|---|---|---|---|
|
Biochemical Markers of Bone Turnover: Procollagen Type 1 N-terminal Propeptide (P1NP)
Baseline
|
47.66 Microgram per Litre (mcg/L)
Standard Error 1.05
|
45.59 Microgram per Litre (mcg/L)
Standard Error 1.05
|
47.70 Microgram per Litre (mcg/L)
Standard Error 1.05
|
46.62 Microgram per Litre (mcg/L)
Standard Error 1.05
|
46.19 Microgram per Litre (mcg/L)
Standard Error 1.05
|
47.71 Microgram per Litre (mcg/L)
Standard Error 1.05
|
48.57 Microgram per Litre (mcg/L)
Standard Error 1.07
|
|
Biochemical Markers of Bone Turnover: Procollagen Type 1 N-terminal Propeptide (P1NP)
Baseline, Placebo contrast
|
—
|
0.96 Microgram per Litre (mcg/L)
Standard Error 1.07
|
1.00 Microgram per Litre (mcg/L)
Standard Error 1.07
|
0.98 Microgram per Litre (mcg/L)
Standard Error 1.07
|
0.97 Microgram per Litre (mcg/L)
Standard Error 1.07
|
1.00 Microgram per Litre (mcg/L)
Standard Error 1.07
|
1.02 Microgram per Litre (mcg/L)
Standard Error 1.08
|
|
Biochemical Markers of Bone Turnover: Procollagen Type 1 N-terminal Propeptide (P1NP)
Week 4
|
45.32 Microgram per Litre (mcg/L)
Standard Error 1.05
|
49.67 Microgram per Litre (mcg/L)
Standard Error 1.05
|
57.36 Microgram per Litre (mcg/L)
Standard Error 1.05
|
60.27 Microgram per Litre (mcg/L)
Standard Error 1.05
|
63.46 Microgram per Litre (mcg/L)
Standard Error 1.05
|
43.66 Microgram per Litre (mcg/L)
Standard Error 1.05
|
92.74 Microgram per Litre (mcg/L)
Standard Error 1.07
|
|
Biochemical Markers of Bone Turnover: Procollagen Type 1 N-terminal Propeptide (P1NP)
Week 4, Placebo contrast
|
—
|
1.10 Microgram per Litre (mcg/L)
Standard Error 1.07
|
1.27 Microgram per Litre (mcg/L)
Standard Error 1.07
|
1.33 Microgram per Litre (mcg/L)
Standard Error 1.07
|
1.40 Microgram per Litre (mcg/L)
Standard Error 1.07
|
0.96 Microgram per Litre (mcg/L)
Standard Error 1.07
|
2.05 Microgram per Litre (mcg/L)
Standard Error 1.09
|
|
Biochemical Markers of Bone Turnover: Procollagen Type 1 N-terminal Propeptide (P1NP)
Month 3
|
39.53 Microgram per Litre (mcg/L)
Standard Error 1.05
|
49.99 Microgram per Litre (mcg/L)
Standard Error 1.05
|
65.21 Microgram per Litre (mcg/L)
Standard Error 1.05
|
73.68 Microgram per Litre (mcg/L)
Standard Error 1.05
|
86.84 Microgram per Litre (mcg/L)
Standard Error 1.05
|
20.15 Microgram per Litre (mcg/L)
Standard Error 1.05
|
99.74 Microgram per Litre (mcg/L)
Standard Error 1.08
|
|
Biochemical Markers of Bone Turnover: Procollagen Type 1 N-terminal Propeptide (P1NP)
Month 3, Placebo contrast
|
—
|
1.26 Microgram per Litre (mcg/L)
Standard Error 1.08
|
1.65 Microgram per Litre (mcg/L)
Standard Error 1.08
|
1.86 Microgram per Litre (mcg/L)
Standard Error 1.08
|
2.20 Microgram per Litre (mcg/L)
Standard Error 1.08
|
0.51 Microgram per Litre (mcg/L)
Standard Error 1.07
|
2.52 Microgram per Litre (mcg/L)
Standard Error 1.09
|
|
Biochemical Markers of Bone Turnover: Procollagen Type 1 N-terminal Propeptide (P1NP)
Month 6
|
38.41 Microgram per Litre (mcg/L)
Standard Error 1.05
|
56.37 Microgram per Litre (mcg/L)
Standard Error 1.05
|
75.73 Microgram per Litre (mcg/L)
Standard Error 1.06
|
90.55 Microgram per Litre (mcg/L)
Standard Error 1.05
|
104.6 Microgram per Litre (mcg/L)
Standard Error 1.05
|
16.41 Microgram per Litre (mcg/L)
Standard Error 1.05
|
117.8 Microgram per Litre (mcg/L)
Standard Error 1.08
|
|
Biochemical Markers of Bone Turnover: Procollagen Type 1 N-terminal Propeptide (P1NP)
Month 6, Placebo contrast
|
—
|
1.47 Microgram per Litre (mcg/L)
Standard Error 1.08
|
1.97 Microgram per Litre (mcg/L)
Standard Error 1.08
|
2.36 Microgram per Litre (mcg/L)
Standard Error 1.08
|
2.72 Microgram per Litre (mcg/L)
Standard Error 1.08
|
0.43 Microgram per Litre (mcg/L)
Standard Error 1.08
|
3.07 Microgram per Litre (mcg/L)
Standard Error 1.09
|
|
Biochemical Markers of Bone Turnover: Procollagen Type 1 N-terminal Propeptide (P1NP)
Month 12
|
40.74 Microgram per Litre (mcg/L)
Standard Error 1.05
|
61.43 Microgram per Litre (mcg/L)
Standard Error 1.05
|
82.69 Microgram per Litre (mcg/L)
Standard Error 1.05
|
98.04 Microgram per Litre (mcg/L)
Standard Error 1.05
|
112.6 Microgram per Litre (mcg/L)
Standard Error 1.05
|
16.98 Microgram per Litre (mcg/L)
Standard Error 1.05
|
119.0 Microgram per Litre (mcg/L)
Standard Error 1.07
|
|
Biochemical Markers of Bone Turnover: Procollagen Type 1 N-terminal Propeptide (P1NP)
Month 12, Placebo contrast
|
—
|
1.51 Microgram per Litre (mcg/L)
Standard Error 1.08
|
2.03 Microgram per Litre (mcg/L)
Standard Error 1.08
|
2.41 Microgram per Litre (mcg/L)
Standard Error 1.08
|
2.76 Microgram per Litre (mcg/L)
Standard Error 1.08
|
0.42 Microgram per Litre (mcg/L)
Standard Error 1.08
|
2.92 Microgram per Litre (mcg/L)
Standard Error 1.09
|
SECONDARY outcome
Timeframe: Baseline (Day 0), Week 4, Month 3, 6, and 12Population: Intent-to-Treat population. Only those participants available at the specified time points were analyzed.
Blood samples were collected at Baseline (Day 0), Week 4, Month 3, 6, and 12 for measurement of BALP.
Outcome measures
| Measure |
Placebo
n=90 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=87 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=82 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=88 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
n=87 Participants
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.
|
Alendronate, 70 mg, Capsule, OW
n=89 Participants
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.
|
Teriparatide, 20 mcg, SC Injection, OD
n=41 Participants
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.
|
|---|---|---|---|---|---|---|---|
|
Biochemical Markers of Bone Turnover: Bone Specific Alkaline Phosphatase (BALP)
Month 12, Placebo contrast
|
—
|
1.26 mcg/L
Standard Error 1.06
|
1.42 mcg/L
Standard Error 1.06
|
1.76 mcg/L
Standard Error 1.06
|
1.76 mcg/L
Standard Error 1.06
|
0.64 mcg/L
Standard Error 1.06
|
1.44 mcg/L
Standard Error 1.07
|
|
Biochemical Markers of Bone Turnover: Bone Specific Alkaline Phosphatase (BALP)
Baseline
|
14.46 mcg/L
Standard Error 1.04
|
14.96 mcg/L
Standard Error 1.04
|
14.24 mcg/L
Standard Error 1.04
|
15.06 mcg/L
Standard Error 1.04
|
14.12 mcg/L
Standard Error 1.04
|
14.31 mcg/L
Standard Error 1.04
|
14.50 mcg/L
Standard Error 1.05
|
|
Biochemical Markers of Bone Turnover: Bone Specific Alkaline Phosphatase (BALP)
Baseline, Placebo contrast
|
—
|
1.03 mcg/L
Standard Error 1.05
|
0.98 mcg/L
Standard Error 1.05
|
1.04 mcg/L
Standard Error 1.05
|
0.98 mcg/L
Standard Error 1.05
|
0.99 mcg/L
Standard Error 1.05
|
1.00 mcg/L
Standard Error 1.07
|
|
Biochemical Markers of Bone Turnover: Bone Specific Alkaline Phosphatase (BALP)
Week 4
|
14.02 mcg/L
Standard Error 1.04
|
14.72 mcg/L
Standard Error 1.04
|
14.51 mcg/L
Standard Error 1.04
|
15.97 mcg/L
Standard Error 1.04
|
15.72 mcg/L
Standard Error 1.04
|
13.68 mcg/L
Standard Error 1.04
|
16.19 mcg/L
Standard Error 1.06
|
|
Biochemical Markers of Bone Turnover: Bone Specific Alkaline Phosphatase (BALP)
Week 4, Placebo contrast
|
—
|
1.05 mcg/L
Standard Error 1.05
|
1.03 mcg/L
Standard Error 1.06
|
1.14 mcg/L
Standard Error 1.05
|
1.12 mcg/L
Standard Error 1.05
|
0.98 mcg/L
Standard Error 1.05
|
1.15 mcg/L
Standard Error 1.07
|
|
Biochemical Markers of Bone Turnover: Bone Specific Alkaline Phosphatase (BALP)
Month 3
|
12.66 mcg/L
Standard Error 1.04
|
15.23 mcg/L
Standard Error 1.04
|
15.44 mcg/L
Standard Error 1.04
|
18.77 mcg/L
Standard Error 1.04
|
17.85 mcg/L
Standard Error 1.04
|
9.44 mcg/L
Standard Error 1.04
|
16.53 mcg/L
Standard Error 1.06
|
|
Biochemical Markers of Bone Turnover: Bone Specific Alkaline Phosphatase (BALP)
Month 3, Placebo contrast
|
—
|
1.20 mcg/L
Standard Error 1.06
|
1.22 mcg/L
Standard Error 1.06
|
1.48 mcg/L
Standard Error 1.06
|
1.41 mcg/L
Standard Error 1.06
|
0.75 mcg/L
Standard Error 1.06
|
1.31 mcg/L
Standard Error 1.07
|
|
Biochemical Markers of Bone Turnover: Bone Specific Alkaline Phosphatase (BALP)
Month 6
|
12.81 mcg/L
Standard Error 1.04
|
16.31 mcg/L
Standard Error 1.04
|
17.43 mcg/L
Standard Error 1.04
|
22.18 mcg/L
Standard Error 1.04
|
21.47 mcg/L
Standard Error 1.04
|
8.36 mcg/L
Standard Error 1.04
|
17.63 mcg/L
Standard Error 1.06
|
|
Biochemical Markers of Bone Turnover: Bone Specific Alkaline Phosphatase (BALP)
Month 6, Placebo contrast
|
—
|
1.27 mcg/L
Standard Error 1.06
|
1.36 mcg/L
Standard Error 1.06
|
1.73 mcg/L
Standard Error 1.06
|
1.68 mcg/L
Standard Error 1.06
|
0.65 mcg/L
Standard Error 1.06
|
1.38 mcg/L
Standard Error 1.07
|
|
Biochemical Markers of Bone Turnover: Bone Specific Alkaline Phosphatase (BALP)
Month 12
|
13.25 mcg/L
Standard Error 1.04
|
16.64 mcg/L
Standard Error 1.04
|
18.80 mcg/L
Standard Error 1.04
|
23.36 mcg/L
Standard Error 1.04
|
23.28 mcg/L
Standard Error 1.04
|
8.42 mcg/L
Standard Error 1.04
|
19.08 mcg/L
Standard Error 1.06
|
SECONDARY outcome
Timeframe: 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 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=76 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=74 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=80 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=78 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
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.
|
Alendronate, 70 mg, Capsule, OW
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.
|
Teriparatide, 20 mcg, SC Injection, OD
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.
|
|---|---|---|---|---|---|---|---|
|
Blood Concentrations of Ronacaleret
Week 4, Pre-dose
|
41.22 nanograms per millilitre (ng/mL)
Standard Deviation 127.438
|
37.24 nanograms per millilitre (ng/mL)
Standard Deviation 36.203
|
85.44 nanograms per millilitre (ng/mL)
Standard Deviation 158.849
|
79.40 nanograms per millilitre (ng/mL)
Standard Deviation 74.083
|
—
|
—
|
—
|
|
Blood Concentrations of Ronacaleret
Week 4, 8-12 h post dose
|
204.82 nanograms per millilitre (ng/mL)
Standard Deviation 183.245
|
328.33 nanograms per millilitre (ng/mL)
Standard Deviation 222.061
|
581.08 nanograms per millilitre (ng/mL)
Standard Deviation 360.031
|
685.14 nanograms per millilitre (ng/mL)
Standard Deviation 450.467
|
—
|
—
|
—
|
|
Blood Concentrations of Ronacaleret
Month 6, Pre-dose
|
21.37 nanograms per millilitre (ng/mL)
Standard Deviation 19.769
|
65.94 nanograms per millilitre (ng/mL)
Standard Deviation 214.325
|
74.12 nanograms per millilitre (ng/mL)
Standard Deviation 146.094
|
117.94 nanograms per millilitre (ng/mL)
Standard Deviation 288.413
|
—
|
—
|
—
|
|
Blood Concentrations of Ronacaleret
Month 6, 1-4 h post dose
|
644.90 nanograms per millilitre (ng/mL)
Standard Deviation 408.282
|
1308.35 nanograms per millilitre (ng/mL)
Standard Deviation 943.397
|
1610.74 nanograms per millilitre (ng/mL)
Standard Deviation 1016.608
|
2054.71 nanograms per millilitre (ng/mL)
Standard Deviation 1499.079
|
—
|
—
|
—
|
|
Blood Concentrations of Ronacaleret
Month 6, 8-12 h post dose
|
186.69 nanograms per millilitre (ng/mL)
Standard Deviation 101.326
|
385.03 nanograms per millilitre (ng/mL)
Standard Deviation 284.963
|
576.35 nanograms per millilitre (ng/mL)
Standard Deviation 382.494
|
796.99 nanograms per millilitre (ng/mL)
Standard Deviation 640.016
|
—
|
—
|
—
|
|
Blood Concentrations of Ronacaleret
Month 6, 24 h post dose
|
186.21 nanograms per millilitre (ng/mL)
Standard Deviation 151.855
|
290.74 nanograms per millilitre (ng/mL)
Standard Deviation 125.486
|
578.63 nanograms per millilitre (ng/mL)
Standard Deviation 398.915
|
473.41 nanograms per millilitre (ng/mL)
Standard Deviation 237.671
|
—
|
—
|
—
|
|
Blood Concentrations of Ronacaleret
Month 12, Pre-dose
|
20.68 nanograms per millilitre (ng/mL)
Standard Deviation 15.971
|
33.47 nanograms per millilitre (ng/mL)
Standard Deviation 26.747
|
147.63 nanograms per millilitre (ng/mL)
Standard Deviation 370.860
|
114.83 nanograms per millilitre (ng/mL)
Standard Deviation 179.448
|
—
|
—
|
—
|
|
Blood Concentrations of Ronacaleret
Month 12, 1-4 h post dose
|
779.92 nanograms per millilitre (ng/mL)
Standard Deviation 465.356
|
999.63 nanograms per millilitre (ng/mL)
Standard Deviation 659.880
|
1819.53 nanograms per millilitre (ng/mL)
Standard Deviation 1021.984
|
2128.24 nanograms per millilitre (ng/mL)
Standard Deviation 1549.003
|
—
|
—
|
—
|
|
Blood Concentrations of Ronacaleret
Month 12, 8-12 h post dose
|
203.39 nanograms per millilitre (ng/mL)
Standard Deviation 124.866
|
262.20 nanograms per millilitre (ng/mL)
Standard Deviation 137.152
|
651.95 nanograms per millilitre (ng/mL)
Standard Deviation 391.752
|
740.18 nanograms per millilitre (ng/mL)
Standard Deviation 679.348
|
—
|
—
|
—
|
|
Blood Concentrations of Ronacaleret
Month 12, 24 h post dose
|
187.23 nanograms per millilitre (ng/mL)
Standard Deviation 100.001
|
297.20 nanograms per millilitre (ng/mL)
Standard Deviation 146.806
|
626.72 nanograms per millilitre (ng/mL)
Standard Deviation 231.777
|
512.65 nanograms per millilitre (ng/mL)
Standard Deviation 314.692
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 12Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=13 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=14 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=14 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=11 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
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.
|
Alendronate, 70 mg, Capsule, OW
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.
|
Teriparatide, 20 mcg, SC Injection, OD
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.
|
|---|---|---|---|---|---|---|---|
|
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
AUC 0-t, Month 6
|
2495.8751 nanogram*hour per millilitre (ng*hr/mL)
Geometric Coefficient of Variation 53.13
|
4575.8746 nanogram*hour per millilitre (ng*hr/mL)
Geometric Coefficient of Variation 35.50
|
7545.3302 nanogram*hour per millilitre (ng*hr/mL)
Geometric Coefficient of Variation 42.26
|
6712.0537 nanogram*hour per millilitre (ng*hr/mL)
Geometric Coefficient of Variation 79.69
|
—
|
—
|
—
|
|
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
AUC 0-t, Month 12
|
2766.6822 nanogram*hour per millilitre (ng*hr/mL)
Geometric Coefficient of Variation 64.20
|
4548.6490 nanogram*hour per millilitre (ng*hr/mL)
Geometric Coefficient of Variation 43.87
|
9259.3127 nanogram*hour per millilitre (ng*hr/mL)
Geometric Coefficient of Variation 37.74
|
6798.4219 nanogram*hour per millilitre (ng*hr/mL)
Geometric Coefficient of Variation 65.17
|
—
|
—
|
—
|
|
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
AUC 0-tau, Month 6
|
3628.0901 nanogram*hour per millilitre (ng*hr/mL)
Geometric Coefficient of Variation 66.72
|
6428.5540 nanogram*hour per millilitre (ng*hr/mL)
Geometric Coefficient of Variation 36.62
|
10825.9083 nanogram*hour per millilitre (ng*hr/mL)
Geometric Coefficient of Variation 50.48
|
9810.4614 nanogram*hour per millilitre (ng*hr/mL)
Geometric Coefficient of Variation 80.08
|
—
|
—
|
—
|
|
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
AUC 0-tau, Month 12
|
3922.9369 nanogram*hour per millilitre (ng*hr/mL)
Geometric Coefficient of Variation 75.72
|
6455.1756 nanogram*hour per millilitre (ng*hr/mL)
Geometric Coefficient of Variation 42.03
|
14827.6940 nanogram*hour per millilitre (ng*hr/mL)
Geometric Coefficient of Variation 38.28
|
10079.2847 nanogram*hour per millilitre (ng*hr/mL)
Geometric Coefficient of Variation 71.01
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 12Population: Pharmacokinetic parameter population.
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.
Outcome measures
| Measure |
Placebo
n=13 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=14 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=14 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=11 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
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.
|
Alendronate, 70 mg, Capsule, OW
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.
|
Teriparatide, 20 mcg, SC Injection, OD
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.
|
|---|---|---|---|---|---|---|---|
|
Maximum Blood Concentration (Cmax) of Ronacaleret
Cmax. Month 6
|
572.10 ng/mL
Geometric Coefficient of Variation 44.79
|
1050.42 ng/mL
Geometric Coefficient of Variation 40.82
|
1756.45 ng/mL
Geometric Coefficient of Variation 52.80
|
1556.58 ng/mL
Geometric Coefficient of Variation 76.83
|
—
|
—
|
—
|
|
Maximum Blood Concentration (Cmax) of Ronacaleret
Cmax. Month 12
|
661.70 ng/mL
Geometric Coefficient of Variation 74.39
|
999.91 ng/mL
Geometric Coefficient of Variation 37.18
|
2254.26 ng/mL
Geometric Coefficient of Variation 41.57
|
1506.45 ng/mL
Geometric Coefficient of Variation 63.78
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 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 12Population: Pharmacokinetic parameters population. Only those participants available at the specified time points were analyzed.
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.
Outcome measures
| Measure |
Placebo
n=13 Participants
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.
|
Ronacaleret, 100 mg Tablet, OD
n=14 Participants
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.
|
Ronacaleret, 200 mg Tablet, OD
n=14 Participants
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.
|
Ronacaleret, 300 mg Tablet, OD
n=11 Participants
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.
|
Ronacaleret, 400 mg Tablet, OD
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.
|
Alendronate, 70 mg, Capsule, OW
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.
|
Teriparatide, 20 mcg, SC Injection, OD
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.
|
|---|---|---|---|---|---|---|---|
|
Time Required to Achieve Maximum Concentration of Ronacaleret in Blood (Tmax)
Tmax, Month 6
|
1.483 h
Interval 0.98 to 4.02
|
1.250 h
Interval 0.67 to 3.03
|
1.700 h
Interval 0.33 to 3.02
|
1.500 h
Interval 0.67 to 4.07
|
—
|
—
|
—
|
|
Time Required to Achieve Maximum Concentration of Ronacaleret in Blood (Tmax)
Tmax, Month 12
|
1.000 h
Interval 0.33 to 4.0
|
1.500 h
Interval 0.67 to 2.95
|
1.500 h
Interval 0.0 to 2.58
|
1.500 h
Interval 0.33 to 3.0
|
—
|
—
|
—
|
Adverse Events
Placebo
Serious events: 0 serious events
Other events: 54 other events
Deaths: 0 deaths
Ronacaleret, 100 mg Tablet, OD
Serious events: 2 serious events
Other events: 54 other events
Deaths: 0 deaths
Ronacaleret, 200 mg Tablet, OD
Serious events: 5 serious events
Other events: 57 other events
Deaths: 0 deaths
Ronacaleret, 300 mg Tablet, OD
Serious events: 7 serious events
Other events: 55 other events
Deaths: 0 deaths
Ronacaleret, 400 mg Tablet, OD
Serious events: 3 serious events
Other events: 61 other events
Deaths: 0 deaths
Alendronate, 70 mg, Capsule, OW
Serious events: 6 serious events
Other events: 46 other events
Deaths: 0 deaths
Teriparatide, 20 mcg, SC Injection, OD
Serious events: 4 serious events
Other events: 30 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=90 participants at risk
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.
|
Ronacaleret, 100 mg Tablet, OD
n=87 participants at risk
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.
|
Ronacaleret, 200 mg Tablet, OD
n=82 participants at risk
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.
|
Ronacaleret, 300 mg Tablet, OD
n=88 participants at risk
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.
|
Ronacaleret, 400 mg Tablet, OD
n=87 participants at risk
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.
|
Alendronate, 70 mg, Capsule, OW
n=89 participants at risk
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.
|
Teriparatide, 20 mcg, SC Injection, OD
n=41 participants at risk
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.
|
|---|---|---|---|---|---|---|---|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Injury, poisoning and procedural complications
Nerve injury
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.4%
1/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Cardiac disorders
Acute myocardial infarction
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Cardiac disorders
Arrhythmia
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Cardiac disorders
Atrioventricular block
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic malignant melanoma
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroma
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-Hodgkin's lymphoma
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.2%
1/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal neoplasm
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.2%
1/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Infections and infestations
Appendicitis
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Infections and infestations
Infection
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Infections and infestations
Pulmonary tuberculosis
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.2%
1/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Nervous system disorders
Loss of consciousness
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Nervous system disorders
Syncope
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.2%
1/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.4%
1/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Gastrointestinal disorders
Upper gastrointestinal haemorrhage
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
General disorders
Chest pain
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.4%
1/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
General disorders
Hyperplasia
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.4%
1/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Reproductive system and breast disorders
Cystocele
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.2%
1/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Reproductive system and breast disorders
Ovarian cyst
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Investigations
Smear cervix abnormal
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.4%
1/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Respiratory, thoracic and mediastinal disorders
Nasal septum deviation
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.4%
1/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Surgical and medical procedures
Salpingo-oophorectomy
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Vascular disorders
Hypertension
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
Other adverse events
| Measure |
Placebo
n=90 participants at risk
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.
|
Ronacaleret, 100 mg Tablet, OD
n=87 participants at risk
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.
|
Ronacaleret, 200 mg Tablet, OD
n=82 participants at risk
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.
|
Ronacaleret, 300 mg Tablet, OD
n=88 participants at risk
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.
|
Ronacaleret, 400 mg Tablet, OD
n=87 participants at risk
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.
|
Alendronate, 70 mg, Capsule, OW
n=89 participants at risk
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.
|
Teriparatide, 20 mcg, SC Injection, OD
n=41 participants at risk
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.
|
|---|---|---|---|---|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
18.9%
17/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
18.4%
16/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
15.9%
13/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
13.6%
12/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
18.4%
16/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
13.5%
12/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
17.1%
7/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Infections and infestations
Influenza
|
7.8%
7/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
6.9%
6/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
6.1%
5/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
6.8%
6/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
10.3%
9/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
7.9%
7/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
9.8%
4/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Infections and infestations
Upper respiratory tract infection
|
5.6%
5/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
5.7%
5/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
4.9%
4/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.3%
2/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
9.2%
8/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
3.4%
3/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
4.9%
2/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Infections and infestations
Bronchitis
|
5.6%
5/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
4.6%
4/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
3.7%
3/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
4.5%
4/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.2%
2/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.4%
1/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Infections and infestations
Urinary tract infection
|
3.3%
3/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
4.6%
4/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
7.3%
6/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
3.4%
3/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
4.9%
2/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Infections and infestations
Gastroenteritis
|
2.2%
2/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
5.7%
5/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.3%
2/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.2%
2/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
9.8%
4/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Infections and infestations
Tooth infection
|
1.1%
1/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.3%
2/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
4.5%
4/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.2%
2/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
7.3%
3/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Gastrointestinal disorders
Diarrhoea
|
5.6%
5/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
6.9%
6/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
9.8%
8/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
12.5%
11/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
13.8%
12/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
5.6%
5/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.4%
1/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Gastrointestinal disorders
Nausea
|
4.4%
4/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
7.3%
6/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
10.2%
9/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
12.6%
11/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
6.7%
6/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
4.9%
2/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Gastrointestinal disorders
Dyspepsia
|
4.4%
4/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
6.9%
6/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
3.7%
3/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
6.8%
6/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
3.4%
3/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
4.5%
4/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
7.3%
3/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Gastrointestinal disorders
Constipation
|
2.2%
2/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
5.7%
5/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
4.9%
4/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
10.2%
9/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
5.7%
5/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.2%
2/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Gastrointestinal disorders
Abdominal pain upper
|
6.7%
6/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
3.4%
3/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
7.3%
6/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
4.5%
4/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
5.7%
5/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
3.4%
3/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.3%
2/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.6%
5/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
8.0%
7/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
11.0%
9/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
5.7%
5/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
11.5%
10/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
7.9%
7/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
12.2%
5/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.1%
10/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
6.9%
6/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.4%
2/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
6.8%
6/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
6.9%
6/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
5.6%
5/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
7.3%
3/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
3.3%
3/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
3.4%
3/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.4%
2/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
4.6%
4/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
3.4%
3/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
9.8%
4/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
2.2%
2/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
5.7%
5/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.4%
2/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.3%
2/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
9.8%
4/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
3.3%
3/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.3%
2/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.2%
1/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
5.6%
5/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Nervous system disorders
Headache
|
7.8%
7/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
5.7%
5/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
6.1%
5/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
4.5%
4/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
4.6%
4/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
9.0%
8/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
14.6%
6/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Nervous system disorders
Dizziness
|
4.4%
4/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
5.7%
5/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
9.8%
8/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
5.7%
5/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
11.5%
10/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
14.6%
6/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Vascular disorders
Hypertension
|
4.4%
4/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
5.7%
5/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
6.1%
5/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.3%
2/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
3.4%
3/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
3.4%
3/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
4.9%
2/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.6%
5/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
4.6%
4/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
3.7%
3/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.3%
2/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.3%
2/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.2%
2/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Cardiac disorders
Palpitations
|
1.1%
1/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
4.5%
4/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.3%
2/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
7.3%
3/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
|
Injury, poisoning and procedural complications
Fall
|
1.1%
1/90 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
3.7%
3/82 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
2.3%
2/88 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
5.7%
5/87 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
1.1%
1/89 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
0.00%
0/41 • Up to Follow-up visit (12 month and 2 weeks)
Intent-to-Treat population was used to report AEs
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER