E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of postmenopausal osteoporosis in patients at risk of vitamin D insufficiency. |
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E.1.1.1 | Medical condition in easily understood language |
Treatment of postmenopausal osteoporosis in patients at risk of vitamin D insufficiency. |
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E.1.1.2 | Therapeutic area | Body processes [G] - Bones and nerves physological processes [G11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10031285 |
E.1.2 | Term | Osteoporosis postmenopausal |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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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 main objective of the present trial is to estimate the proportion of patients with 25-hydroxy vitamin D insufficiency (<15 ng/ml) after 15 weeks of treatment with two oral test products containing alendronate sodium/cholecalciferol 70 mg/0.07 mg or 70 mg/0.14 mg (Alendronate/cholecalciferol (Teva Pharmaceutical Industries Ltd.)) as compared to alendronate alone Fosamax®. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives of the present trial are: - To evaluate the efficacy of both test products as compared to Fosamax® alone in reducing the proportion of patients with 25-hydroxy vitamin D deficiency (<9 ng/ml) after 15 weeks of treatment. - To assess the difference in the mean serum 25-hydroxy vitamin D between both test products and the reference product after 15 weeks of treatment. - To assess the percent change from baseline in the serum concentrations of intact serum parathyroid hormone (iPTH) between both test products and the reference product after 15 weeks of treatment. - To evaluate the changes from baseline in the rate of bone turnover as assessed by biochemical markers (bone-specific alkaline phosphatase (BSAP) and urine N-telopeptides of type 1 colloagen corrected for creatinine (NTx/Cr)). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. 18 years and older 2. Patients in good general health, according to the investigator‟s judgment 3. Serum 25-hydroxy vitamin D ≥9 ng/ml 4. Normal (within reference range) iPTH and BSAP for patients with serum 25-hydroxy vitamin D ≥9 ng/ml and <15 ng/ml 5. Postmenopausal women defined as one of the following: - more than 6 months amenorrhea in patients ≥55 years OR - more than 18 months amenorrhea in patients <55 years OR - baseline serum FSH >35 IU/l in patients <55 years and less than 18 months amenorrhea OR - surgical menopause since more than 4 weeks. 6. Recent (within the last 6 months) bone mineral density (BMD) Tscore determined by dual energy X-ray absorptiometry (DEXA) of either lumbar spine or hip of ≤ -2.5 (≥2.5 standard deviations below the mean for normal postmenopausal women) 7. Patient agrees to apply sunscreen and limit sunlight-exposure to 1 hour per day during the study 8. Patient agrees to avoid tanning beds/UV therapy within 14 days of study start, and during the study 9. Patients with ability to follow study instructions and likely to attend and complete all required visits 10. Written informed consent of the patient |
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E.4 | Principal exclusion criteria |
1. Hypersensitivity to the active substances or to any of the excipients, or to any related drug 2. Bone fractures within 3 months prior to screening 3. Inability to stand or sit upright for at least 30 minutes 4. Inability to take the study drugs as recommended: after getting up for the day with a full glass of water (not less than 200 ml) 5. Active upper gastrointestinal problems, such as dysphagia, esophageal disease, gastritis, duodenitis, ulcers 6. Recent history (within the previous year) of major gastrointestinal disease such as peptic ulcer, or active gastrointestinal bleeding, or surgery of the upper gastrointestinal tract other than pyloroplasty 7. Known Barrett's esophagus 8. Malabsorption 9. Hypocalcemia: serum calcium <2.1 mmol/l (9 mg/dl) 10. Concomitant malignancy except carcinoma in situ not needing other than local therapy 11. History of solid tumors not curatively treated or showing a recurrence within the last 5 years 12. Concomitant untreated severe periodontal disease 13. Renal impairment (glomerular filtration rate less than 35 ml/min) 14. Presence of bone or mineral metabolism disorders, other than idiopathic osteoporosis (e.g. hyperparathyroidism, hyperthyroidism, osteomalacia of other origin, Paget‟s disease of bone, glucocorticoid-induced osteoporosis) 15. Diseases associated with unregulated overproduction of calcitriol (e.g. leukemia, lymphoma, sarcoidosis). 16. Previous or concomitant intake of drugs and/or food additives restricted by the protocol (for a complete list please see chapter 8.6.6, page 38). 17. Pregnancy or lactation 18. Simultaneous participation in another clinical study or participation in any clinical study involving an investigational drug within 3 months prior to start of the present study 19. Severe physical or mental concomitant diseases that might hamper the realization of the trial according to protocol 20. History of alcohol or drug addiction 21. Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, scope and possible consequences of the study 22. Unreliability or lack of cooperation |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint in the present trial is the proportion of patients with 25-hydroxy vitamin D insufficiency (<15 ng/ml) after 15 weeks of treatment. This endpoint undergoes descriptive and comparative statistical evaluation |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
after 15 weeks of treatment |
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E.5.2 | Secondary end point(s) |
a) proportion of patients with 25-hydroxy vitamin D deficiency (<9 ng/ml) after 15 weeks of treatment, b) mean serum concentration of 25-hydroxy vitamin D after 15 weeks of treatment, c) percent change from baseline in intact serum parathyroid hormone (iPTH) after 15 weeks of treatment d) changes from baseline in the rate of bone turnover as assessed by biochemical markers (bone-specific alkaline phosphatase (BSAP) and urine N-telopeptides of type 1 colloagen corrected for creatinine (NTx/Cr)) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
after 15 weeks of treatment |
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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 | Yes |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
verum-controlled with double dummy technique |
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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.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 38 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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The clinical end of the trial is 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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |