Osteoporosis
Conditions
Keywords
Lumbar Spine Bone Mineral Density (BMD)
Brief summary
The objective is to show superior efficacy of PTH (1-84) over risedronate in treating osteoporotic women for 12 months after having previously been treated with PTH (1-84) for 12 months followed by 12 months treatment with risedronate.
Interventions
Self-administered (100 μg in a volume of 71.4 μL) daily as a subcutaneous injection in the abdomen using the Preotact pen.
DRUGRisedronate
Orally once weekly as one 35 mg tablet.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Women above the age of 50 years with the diagnosis of postmenopausal 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 above 50 years old? 3. Is the subject postmenopausal (more than 5 years) - in the judgement of the investigator? 4. Does the subject have primary osteoporosis with a lumbar spine T score \< -3.0 SD (at lumbar spine L1-L4, with a minimum of two evaluable vertebrae)? 5. Does the subject have a life expectancy of \>3 years? 6. Is the subject able to self-inject PTH (1-84), (or to have PTH (1-84) injection by a helper)?
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Lumbar Spine BMD From Start of Trial Period III Until End of Trial Period III. | 12 months | BMD was measured by Dual X-ray Absorptiometry (DXA). |
Countries
Denmark
Participant flow
Recruitment details
The trial was divided into 3 consecutive open-label treatment phases of 12 months with randomisation after Trial Period II. From 407 enrolled patients in total, 2 patients were enrolled but were never exposed to trial treatment. Thus, 405 patients in total received trial treatment.
Pre-assignment details
* Period I: total number of 405 patients were included and all received PTH(1-84) treatment for 1 year * Period II: of those 405 patients, 282 continued into the 2. year and all received risedronate * Period III: during the 3. year, the remaining 268 patients were randomised to either PTH(1-84) (=136 patients) or risedronate (=132 patients)
Participants by arm
| Arm | Count |
|---|---|
| PTH(1-84) or Risedronate * PTH(1-84) received by 405 participants in Trial Period I
* of those 405 participants, 282 received Risedronate in Trial Period II
* of those 282 participants, 268 participant remained and 136 received PTH(1-84) and 132 received Risedronate in Trial Period III | 405 |
| Total | 405 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Trial Period I (12 Months) | Adverse Event | 84 | 0 |
| Trial Period I (12 Months) | Non-compliance | 3 | 0 |
| Trial Period I (12 Months) | Other | 11 | 0 |
| Trial Period I (12 Months) | Withdrawal by Subject | 27 | 0 |
| Trial Period II (12 Months) | Adverse Event | 0 | 6 |
| Trial Period II (12 Months) | Non-compliance | 0 | 2 |
| Trial Period II (12 Months) | Other | 0 | 1 |
| Trial Period II (12 Months) | Withdrawal by Subject | 0 | 5 |
| Trial Period III (12 Months) | Adverse Event | 13 | 3 |
| Trial Period III (12 Months) | Other | 1 | 1 |
| Trial Period III (12 Months) | Withdrawal by Subject | 4 | 1 |
Baseline characteristics
| Characteristic | PTH(1-84) or Risedronate |
|---|---|
| Age, Customized Trial Period III / PTH(1-84) | 63.4 years STANDARD_DEVIATION 6.94 |
| Age, Customized Trial Period III / Risedronate | 64.7 years STANDARD_DEVIATION 7.91 |
| Age, Customized Trial Period II / Risedronate | 64.2 years STANDARD_DEVIATION 7.43 |
| Age, Customized Trial Period I / PTH(1-84) | 64.6 years STANDARD_DEVIATION 7.46 |
| Body Mass Index Trial Period III / PTH(1-84) | 24.06 kg/m^2 STANDARD_DEVIATION 3.618 |
| Body Mass Index Trial Period III / Risedronate | 24.21 kg/m^2 STANDARD_DEVIATION 3.933 |
| Body Mass Index Trial Period II / Risedronate | 24.11 kg/m^2 STANDARD_DEVIATION 3.788 |
| Body Mass Index Trial Period I / PTH(1-84) | 24.06 kg/m^2 STANDARD_DEVIATION 3.861 |
| Height Trial Period III / PTH(1-84) | 157.6 cm STANDARD_DEVIATION 6.21 |
| Height Trial Period III / Risedronate | 157.4 cm STANDARD_DEVIATION 6.86 |
| Height Trial Period II / Risedronate | 157.5 cm STANDARD_DEVIATION 6.48 |
| Height Trial Period I / PTH(1-84) | 157.4 cm STANDARD_DEVIATION 6.4 |
| Lumbar spine T-score Trial Period III / PTH(1-84) | -3.60 score STANDARD_DEVIATION 0.427 |
| Lumbar spine T-score Trial Period III / Risedronate | -3.63 score STANDARD_DEVIATION 0.518 |
| Lumbar spine T-score Trial Period II / Risedronate | -3.62 score STANDARD_DEVIATION 0.472 |
| Lumbar spine T-score Trial Period I / PTH(1-84) | -3.61 score STANDARD_DEVIATION 0.49 |
| Prevalent non-vertebral fragility fractures Trial Period III / PTH(1-84): hip fractures | 1 participants |
| Prevalent non-vertebral fragility fractures Trial Period III / PTH(1-84): others | 28 participants |
| Prevalent non-vertebral fragility fractures Trial Period III / PTH(1-84): wrist fractures | 22 participants |
| Prevalent non-vertebral fragility fractures Trial Period III / Risedronate: hip fractures | 3 participants |
| Prevalent non-vertebral fragility fractures Trial Period III / Risedronate: others | 27 participants |
| Prevalent non-vertebral fragility fractures Trial Period III / Risedronate: wrist fractures | 25 participants |
| Prevalent non-vertebral fragility fractures Trial Period II / Risedronate: hip fractures | 5 participants |
| Prevalent non-vertebral fragility fractures Trial Period II / Risedronate: others | 59 participants |
| Prevalent non-vertebral fragility fractures Trial Period II / Risedronate: wrist fractures | 50 participants |
| Prevalent non-vertebral fragility fractures Trial Period I / PTH(1-84): hip fractures | 9 participants |
| Prevalent non-vertebral fragility fractures Trial Period I / PTH(1-84): others | 93 participants |
| Prevalent non-vertebral fragility fractures Trial Period I / PTH(1-84): wrist fractures | 78 participants |
| Prevalent vertebral fractures Trial Period III / PTH(1-84) | 37 participants |
| Prevalent vertebral fractures Trial Period III / Risedronate | 29 participants |
| Prevalent vertebral fractures Trial Period II / Risedronate | 71 participants |
| Prevalent vertebral fractures Trial Period I / PTH(1-84) | 105 participants |
| Serum Calcium Trial Period III / PTH(1-84) | 2.337 mmol/L STANDARD_DEVIATION 0.0961 |
| Serum Calcium Trial Period III / Risedronate | 2.339 mmol/L STANDARD_DEVIATION 0.1041 |
| Serum Calcium Trial Period II / Risedronate | 2.337 mmol/L STANDARD_DEVIATION 0.0999 |
| Serum Calcium Trial Period I / PTH(1-84) | 2.338 mmol/L STANDARD_DEVIATION 0.1022 |
| Sex/Gender, Customized female | 405 participants |
| Weight Trial Period III / PTH(1-84) | 59.6 kg STANDARD_DEVIATION 8.66 |
| Weight Trial Period III / Risedronate | 59.8 kg STANDARD_DEVIATION 9.57 |
| Weight Trial Period II / Risedronate | 59.7 kg STANDARD_DEVIATION 9.17 |
| Weight Trial Period I / PTH(1-84) | 59.5 kg STANDARD_DEVIATION 9.39 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 365 / 405 | 95 / 282 |
| serious Total, serious adverse events | 33 / 405 | 32 / 282 |
Outcome results
Primary
Change in Lumbar Spine BMD From Start of Trial Period III Until End of Trial Period III.
BMD was measured by Dual X-ray Absorptiometry (DXA).
Time frame: 12 months
Population: All randomized patients made the Full Analysis Set which was used for the primary and secondary analyses according to intention-to-treat principles. One participant excluded due to missing baseline data at trial period III entry, thus no data could be carried forward for this patient. Missing values imputed by Last Observation Carried Forward.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| PTH (1-84) | Change in Lumbar Spine BMD From Start of Trial Period III Until End of Trial Period III. | 1.002 Percentage Change | Standard Error 1.0037 |
| Risedronate | Change in Lumbar Spine BMD From Start of Trial Period III Until End of Trial Period III. | 0.990 Percentage Change | Standard Error 1.0034 |
Comparison: An analysis of covariance (ANCOVA) model was used including treatment group, stratum and pooled centre as fixed effects and log (BMD at Baseline III (month 24)) as a covariate (log-normally distributed data assumed). Least square mean change from baseline III (month 24), 95% confidence interval and p-value for the treatment effect (PTH (1-84) vs. Risedronate) was calculated. Superiority was claimed if lower limit of the interval was above 1. Results were back-transformed from the log scale.p-value: 0.0195% CI: [1.003, 1.021]ANCOVA