Effect of Full Length Parathyroid Hormone, PTH(1-84) or Strontium Ranelate on Bone Markers in Postmenopausal Women With Primary Osteoporosis (FP-006-IM)

A 24-week, International, Multi Centre, Randomised, Open Label, Parallel Group, Phase IV Clinical Trial Investigating Changes in Bone Formation Markers in Postmenopausal Women With Primary Osteoporosis Treated With Either PTH(1-84) or Strontium Ranelate

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.

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 exclusion criteria and note [**].

Exclusion criteria:

All exclusion criteria must be answered "no" for a subject to be enrolled in the trial.

Has the subject:

1. been treated with SERMS (selective oestrogen receptor modulators) or calcitonin within the last 1 month?

2. ever been treated with any bisphosphonate in intravenous form (i.v.)?

3. been treated with any bisphosphonates (alendronate, risedronate, or other bisphosphonates) for more than 3 years in total, or within the last 6 months?

4. been treated with fluoride for more than 3 months within the last 10 years?

5. ever been treated with strontium ranelate?

6. ever been treated with teriparatide or PTH(1-84)?

7. received or is the subject currently receiving chronic glucocorticosteroid treatment?

   Defined as more or equal to:

   5.0 mg prednisolon or equivalent daily for 3 months during the last year or 2.5 mg prednisolon or equivalent daily for 6 months during the last year. Local and inhalation steroids are permitted.

8. been treated for cancer (other than basocellular skin cancer) within the last 5 years?

9. ever received radiation therapy to the skeleton?

10. ever had malignant disease affecting the skeleton? or does the subject:

11. currently receive antiepileptic medication?

12. take any other medication (other than calcium and vitamin D3) that is known to affect bone metabolism? - according to the investigator's opinion.

13. have any known clinically significant diseases affecting calcium metabolism?

14. have any known history of metabolic bone diseases other than primary osteoporosis including hyperparathyroidism, Paget's disease, osteogenesis imperfecta, or osteomalacia)?

15. have any known history of hypersensitivity to parathyroid hormone or strontium or any of the excipients in the products?

16. have a serum vitamin D3, (serum 25(OH)D) level <20 ng/ml after at least 14 days of calcium and vitamin D3 supplementation? [**]

17. have a serum PTH of > 65 pg/ml and also a total serum calcium value >2.49 mmol/l? [**]

18. have hypercalcaemia (total serum calcium value >2.55 mmol/l), measured after at least 14 days of calcium and vitamin D3 supplementation? [**]

19. have elevated serum alkaline phosphatase? Defined as > 3X ULN [**]

20. have impaired kidney function with creatinine clearance < 30 ml/min (indirect measurement by serum creatinine)? [**]

21. have severe impaired liver function ? [**]

22. have phenylketonuria? or is the subject:

23. at risk of having venous thromboembolism including pulmonary embolism? - according to the investigator's opinion.

24. scheduled for vertebroplasty?

25. currently participating in a clinical trial with an investigational medical product, or has done so within the last 90 days, or plan to do so within the next 32 weeks? Previous and current participation in non-interventional trials is allowed.

[**] exclusion criteria no. 16 to 21 can not be evaluated before the result of the blood sampling (planned within the screening period and after at least 14 days of supplemental calcium/vitamin D3 intake) is available.