Osteoporosis
Conditions
Keywords
postmenopausal women with primary osteoporosis
Brief summary
The primary objective of this trial is to show that PTH(1-84) is superior to strontium ranelate in bone formation measured as changes in bone formation markers over a treatment period of 24 weeks in postmenopausal women with primary osteoporosis.
Interventions
DRUGFull Length Parathyroid Hormone, PTH(1-84)
Once daily subcutaneous injection in the abdomen by self administration
The daily dose of 2 g (one sachet) strontium ranelate was to be mixed in a glass of water and taken immediately after mixing at bedtime at least 2 hours before or after intake of calcium, any food or drinks, other than water
Sponsors
Nycomed
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Postmenopausal women at or above the age of 50, diagnosed with primary osteoporosis may be enrolled in the trial if the following inclusion/
Exclusion criteria
apply. All inclusion criteria must be answered yes for a subject to be enrolled in the trial. 1. Has the subject given informed consent according to local requirements before any trial related activities? (A trial related activity is any procedure that would not have been performed during the routine management of the subject). 2. Is the subject female and at or above the age of 50? 3. Has the subject been postmenopausal for more than 5 years - in the judgement of the investigator? 4. Does the subject have primary osteoporosis and a T-score equal to or lower than -2.5 SD; T-scores must be assessed by DXA at the lumbar spine L1-L4, with a minimum of two assessable vertebrae, or at the total hip (right hip, if there is a right hip prosthesis, left hip can be used. If both hips are replaced the subject can be included with a lumbar scan only). 5. Is the subject currently taking calcium and vitamin D3 or is she willing to start such supplemental treatment and continue throughout the trial period, unless she develops hypercalcaemia? 6. Has the subject been taking supplemental calcium (1,000 mg) and vitamin D3 (800 IU) daily for at least 14 days (after screening) before blood sampling for eligibility evaluation? \[\*\] 7. Is the subject able to self-inject PTH(1-84), or get the injections by a helper? \[\*\] Note that inclusion criteria no. 6 can not be evaluated at the time for screening, must be evaluated at randomisation, visit 2. See also
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in the Bone Formation Marker N-terminal Propeptides of Human Procollagen Type I (P1NP) From Baseline to End of Trial | Baseline and 24 weeks of treatment | P1NP is a bone formation marker that is derived from the amino-terminal propeptides of type I collagen and is considered a quantitative measure of newly formed type I collagen. Bone marker measurements were done by blood analysis. |
| Percentage Change in the Bone Formation Marker Bone Specific Alkaline Phosphatase (BSAP) From Baseline to End of Trial | Baseline and 24 weeks of treatment | BSAP is a marker of bone formation that reflects the cellular activity of osteoblasts. Bone marker measurements were done by blood analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in the Bone Resorption Marker C-Telopeptide Cross-links (CTX) From Baseline to End of Trial | Baseline and 24 weeks of treatment | CTX is a marker of bone resorption, which is a degradation product of bone collagen. Bone marker measurements were done by blood analysis. |
Countries
Denmark
Participant flow
Pre-assignment details
82 subjects were randomized. Of these, one subject was randomized, but consent was withdrawn during the screening period; the subject did not receive any treatment. Therefore, the Intention to treat set (ITT) consisted of 81 subjects.
Participants by arm
| Arm | Count |
|---|---|
| PTH(1-84) Once daily subcutaneous injection | 41 |
| Strontium Ranelate One sachet (2 g) per day, suspended in water | 40 |
| Total | 81 |
Baseline characteristics
| Characteristic | PTH(1-84) | Strontium Ranelate | Total |
|---|---|---|---|
| Age Continuous | 64.0 years STANDARD_DEVIATION 8.64 | 64.9 years STANDARD_DEVIATION 8.49 | 64.4 years STANDARD_DEVIATION 8.52 |
| Sex/Gender, Customized Female | 41 participants | 40 participants | 81 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 29 / 40 | 19 / 40 |
| serious Total, serious adverse events | 2 / 40 | 2 / 40 |
Outcome results
Primary
Percentage Change in the Bone Formation Marker Bone Specific Alkaline Phosphatase (BSAP) From Baseline to End of Trial
BSAP is a marker of bone formation that reflects the cellular activity of osteoblasts. Bone marker measurements were done by blood analysis.
Time frame: Baseline and 24 weeks of treatment
Population: ITT analysis. Number of participants analyzed = number of participants with data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PTH(1-84) | Percentage Change in the Bone Formation Marker Bone Specific Alkaline Phosphatase (BSAP) From Baseline to End of Trial | 129.6 percent change | Standard Deviation 100.3 |
| Strontium Ranelate | Percentage Change in the Bone Formation Marker Bone Specific Alkaline Phosphatase (BSAP) From Baseline to End of Trial | 4.9 percent change | Standard Deviation 22.9 |
Comparison: The bone marker values were log-transformed for the primary analysis as they were heavily skewed. Changes in log-transformed bone marker values were analyzed using an analysis of covariance (ANCOVA) with treatment and center as fixed effects and the baseline bone marker value as a covariate. An F-test was used to test the effect of treatment and the least square means were computed to assess the clinical difference between treatment groups.p-value: <0.000195% CI: [63.8, 127.1]ANCOVA
Primary
Percentage Change in the Bone Formation Marker N-terminal Propeptides of Human Procollagen Type I (P1NP) From Baseline to End of Trial
P1NP is a bone formation marker that is derived from the amino-terminal propeptides of type I collagen and is considered a quantitative measure of newly formed type I collagen. Bone marker measurements were done by blood analysis.
Time frame: Baseline and 24 weeks of treatment
Population: ITT (Intention to Treat) analysis. Number of participants analyzed = number of participants with data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PTH(1-84) | Percentage Change in the Bone Formation Marker N-terminal Propeptides of Human Procollagen Type I (P1NP) From Baseline to End of Trial | 446.1 percent change | Standard Deviation 355.3 |
| Strontium Ranelate | Percentage Change in the Bone Formation Marker N-terminal Propeptides of Human Procollagen Type I (P1NP) From Baseline to End of Trial | -6.2 percent change | Standard Deviation 36.9 |
Comparison: The bone marker values were log-transformed for the primary analysis as they were heavily skewed. Changes in log-transformed bone marker values were analyzed using an analysis of covariance (ANCOVA) with treatment and center as fixed effects and the baseline bone marker value as a covariate. An F-test was used to test the effect of treatment and the least square means were computed to assess the clinical difference between treatment groups.p-value: <0.000195% CI: [256.5, 494.3]ANCOVA
Secondary
Percentage Change in the Bone Resorption Marker C-Telopeptide Cross-links (CTX) From Baseline to End of Trial
CTX is a marker of bone resorption, which is a degradation product of bone collagen. Bone marker measurements were done by blood analysis.
Time frame: Baseline and 24 weeks of treatment
Population: ITT analysis. Number of participants analyzed = number of participants with data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| PTH(1-84) | Percentage Change in the Bone Resorption Marker C-Telopeptide Cross-links (CTX) From Baseline to End of Trial | 153.3 percent change | Standard Deviation 132.4 |
| Strontium Ranelate | Percentage Change in the Bone Resorption Marker C-Telopeptide Cross-links (CTX) From Baseline to End of Trial | -3.7 percent change | Standard Deviation 36 |
Comparison: The bone marker values were log-transformed for the primary analysis as they were heavily skewed. Changes in log-transformed bone marker values were analyzed using an analysis of covariance (ANCOVA) with treatment and center as fixed effects and the baseline bone marker value as a covariate. An F-test was used to test the effect of treatment and the least square means were computed to assess the clinical difference between treatment groups.p-value: <0.000195% CI: [94.8, 191.8]ANCOVA