E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary postmenopausal osteoporosis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10031285 |
E.1.2 | Term | Osteoporosis postmenopausal |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Bone biopsy sub study, implemented by Amendment 3 dated 4-Jan-07, as approved by EMEA on 27-Feb-08: in order to obtain further data on bone safety and bone efficacy of PTH(1-84), evaluation of bone histomorphometric parameters will be included in the trial. This sub study will be performed in subjects that have completed a minimum of 148 weeks of the trial and have consented to participate in the sub study separately. Between weeks 148 to 156 (end of trial period III), a bone biopsy will be performed 5-7 days after two 2-day oral tetracycline labelling given with a 10-day interval. It is expected that a minimum of 24 and a maximum of 50 patients will participate in this sub study. The objective of this sub study is to evaluate the relative histomorphometric parameters in subjects receiving PTH(1-84) in trial period III compared to risedronate and to further confirm the safety of PTH(1-84) treatment. The bone biopsies will be analysed to determine the quantitative effects of the trial treatments (PTH(1-84) and risedronate) during trial period III. The primary efficacy endpoint for the bone biopsy sub trial is the standard histomorphometric measurement Bone Formation Rate. The value will be determined by two dimensional histomorphometry and three dimensional microcomputed tomography.
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E.3 | Principal inclusion criteria |
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 equal to or less than -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?
Bone biopsy sub trial:
6. Is the subject able to self-inject PTH (1-84), (or to have PTH (1-84) injection by a helper)?
7. Has the subject given consent to having a bone biopsy performed?
8. Has the subject completed trial period II in FP-001-IM?
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E.4 | Principal exclusion criteria |
1. Is the subject currently in treatment with Selective Estrogen Receptor Modulators (SERMs) (e.g. raloxifen)? If the SERM treatment is terminated the subject can still be evaluated for eligibility.
2. Has the subject ever been treated with any bisphosphonate other than alendronate or risedronate?
3. Has the subject been treated with alendronate or risedronate for more than 3 years in total?
4. Has the subject during lifetime been treated with both alendronate and risedronate, including sequential treatment?
5. Has the subject during lifetime been treated with strontium > 3 months in total?
6. Has the subject during lifetime been treated with fluoride > 3 months in total?
7. Has the subject during lifetime been treated with teriparatide or PTH (1-84)?
8. Has the subject during lifetime been treated with calcitonin during the last 3 months?
9. Is the subject currently receiving antiepileptic medication?
10. Does the subject take any other medication, that according to investigator’s opinion, is known to affect bone metabolism?
11. Has the subject received or is the subject currently receiving chronic glucocorticosteroid treatment? Defined as more or equal to: • 5.0mg prednisolon or equivalent daily for 3 months during the last year or • 2.5mg prednisolon or equivalent daily for 6 months during the last year
12. Has the subject ever received radiation therapy to the skeleton?
13. Has the subject been treated for cancer (other than basocellular skin cancer) within the last 5 years?
14. Has the subject ever had malignant disease affecting the skeleton?
15. Has the subject ever had breast cancer?
16. Does the subject have any known clinically significant diseases affecting calcium metabolism?
17. Does the subject have any known history of metabolic bone diseases other than primary osteoporosis (including hyperparathyroidism, Paget’s disease, osteogenesis imperfecta, or osteomalacia)?
18. Does the subject have a medical history of abnormalities in oesophagus prohibiting emptying of oesophagus (e.g. achalasia or stricture) and inability to ingest risedronate (should be able to take risedronate upright) judged by the investigator to be significant?
19. Does the subject have any known history of hypersensitivity to parathyroid hormone or risedronate or any of the excipients in the products?
20. Does the subject have any clinically significant conduction abnormalities e.g. second degree atrial ventricular block as assessed by the investigator based on ECG reading?
21. Does the subject have a plasma 25-hydroxyvitamin D level <9.2ng/ml after at least 14 days of calcium and vitamin D supplementation?
22. Does the subject have a plasma PTH of > 65pg/ml and a total serum calcium value >2.49 mmol/l?
23. Does the subject have hypercalcaemia (total serum calcium value >2.55mmol/l) after at least 14 days of calcium supplementation?
24. Does the subject have a clinically significant elevation of serum alkaline phosphatase judged by the investigator?
25. Does the subject have impaired kidney function with creatinine clearance <30ml/min (indirect measurement by serum creatinine)?
26. Does the subject have a 24 hours urinary calcium > 360mg after at least 14 days of calcium supplementation?
27. Has the subject ever shown intolerance to any bisphosphonate?
28. Is the subject scheduled for vertebroplasty?
29. Has the subject participated in a clinical trial with an Investigational Medicinal Product (IMP) during the last 30 days or does the subject plan to participate in such within the next 3 years? (Participation in non-interventional trials is allowed)
Bone biopsy sub trial:
30. Does the subject have an International Normalized Ratio (INR) > 1.2 measured the earliest 1 month before the planed bone biopsy?
31. Is the patient currently in anti-coagulation therapy?
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in lumbar spine BMD (measured by Dual X-ray Absorptiometry (DXA)) from start of trial period III to end of trial period III. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 33 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 10 |