E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Post-menopausal osteoporosis |
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E.1.1.1 | Medical condition in easily understood language |
Osteoporosis occurring after menopause |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10031286 |
E.1.2 | Term | Osteoporosis senile |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10031283 |
E.1.2 | Term | Osteoporosis fracture |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10017082 |
E.1.2 | Term | Fracture due to osteoporosis |
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 |
To assess whether treatment with bisphosphonates combined with vitamin K, in vitamin K deplete elderly women with osteoporosis, will offer additional benefit on skeletal metabolism and reduction of fracture risk.
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion in the cross-sectional part of the study which involves assessment of vitamin K status
1. Informed consent to pre –screen assessment of vitamin K 2. ambulatory post-menopausal women aged between 55-85 years 3. Post-menopausal osteoporosis ( history of previous fragility fractures or BMD evidence of osteoporosis or osteopenia with at least one clinical risk factors such as low BMI, positive family history of osteoporosis) 4. Treatment with a bisphosphonate and calcium/vitamin D supplements or a bisphosphonate and calcium/vitamin D replete for at least 12 months
Inclusion into the randomised controlled trial
1. Informed consent to main study 2. serum vitamin K concentration ≤ 0.40 μg/L |
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E.4 | Principal exclusion criteria |
1. Age <55 years, or > 85 years 2. Male gender 3. severe renal impairment (CKD stage 4 and 5) 4. poor mobility (inability to walk 100 yards unaided) 5. malabsorption (extensive bowel surgery, short bowel) 6. generalised carcinomatosis 7. glucocorticoid therapy 8. inflammatory disorders (e.g. active rheumatoid arthritis, inflammatory bowel disease requiring oral glucocorticoids), 9. Untreated endocrine diseases (e.g. primary hyperparathyroidism, hyperthyroidism). 10. chronic liver disease 11. current treatment with teriparatide or strontium ranelate 12. Participation in a trial with an investigational product within the previous 3 months 13. Serum vitamin K > 0.40 μg/L 14. current treatment with anti-coagulants such as warfarin |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome will be changes in BMD at the lumbar spine, total hip and femoral neck |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
> Secondary outcome measures will be changes in the biochemical parameters including vitamin K status and serum CTX, P1NP, BALP, carboxylated and undercarboxylated osteocalcin (OC), OPG. > Additional secondary outcome measures will also include parameters of bone density and hip geometry at three other hip sites, narrow neck of femur, intertrochanteric and femoral shaft determined using the DXA scan images acquired during the BMD measurements of the hip |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
> During each clinic visit (3, 6, 12, 18 months). > Baseline and 18-months.
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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 | No |
E.6.5 | Efficacy | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
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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Last visit of the last subject |
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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 | |
E.8.9.1 | In the Member State concerned days | |