E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Osteoporosis in postmenopausal women |
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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 | 10031282 |
E.1.2 | Term | Osteoporosis |
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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 primary objective of this study is to demonstrate that the percentage change in BMD of the total hip as measured by DXA at Year 9 relative to Year 6 in patients treated with zoledronic acid for up to 9 years in the CZOL446H2301 core and both extension studies (Group Z9) is significantly greater than in patients treated with zoledronic acid for 6 years in the CZOL446H2301 core and CZOL446H2301E1 studies followed by up to 3 years of placebo in Study CZOL446H2301E2 (Group Z6P3). |
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E.2.2 | Secondary objectives of the trial |
Secondary efficacy objectives:Evaluating the differences between treatment groups with respect to: - The percentage change in total hip and femoral neck BMD at Year 7, 8 and 9 relative to Year 0 for the Z9 group relative to the Z6P3 group - Percent change in the total hip BMD at Year 7 and 8 relative to Year 6 - The percentage change in femoral neck BMD at Year 7, 8 and 9 relative to Year 6 - Relative changes in biochemical markers at Year 7, 8 and 9 compared to Year 0 for the Z9 group relative to the Z6P3 group - The change in height at Year 9 relative to Year 6 for the Z9 group relative to the Z6P3 group - Cumulative incidence of clinical fractures and vertebral fractures at Year 7, 8 and 9 starting from Year 6 for the Z9 group relative to the Z6P3 group
Safety objectives: - Evaluating the adverse event profile, cardiac questionnaire, changes in laboratory, renal and ECG parameters |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Women who have completed Study CZOL446H2301E1 and received at least the 4th and 6th doses of zoledronic in Study CZOL446H2301E1according to the guidelines and instructions provided.
2. Signed written informed consent to participate in the Study CZOL446H2301E2.
3. Patients must be considered ambulatory. Patients can be included who are ambulatory with an assistive device (cane, walker, etc).
4. Patients must have been taking the dosage of calcium and vitamin D required in CZOL446H2301E1(1000 to 1500 mg of elemental calcium and 400 to 1200 IU of vitamin D daily) for at least 3 months prior to entry into the extension CZOL446H2301E2.
5. Patients must have DXA measurements of the hip performed at Visit 11 (Study CZOL446H2301E1 final study visit).
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E.4 | Principal exclusion criteria |
1. Patients who demonstrated a major protocol violation in Study CZOL446H2301E1 or patients for whom the investigator feels participation in Study CZOL446H2301E2 is not appropriate.
2. Any prior use of iv bisphosphonate other than the study drug during Study CZOL446H2301E1 and during the period after completion of Study CZOL446H2301E1 but prior to randomization in Study CZOL446H2301E2.
3. Any use of oral bisphosphonates for more than 1 month total during Study CZOL446H2301E1 and during the period after completion of Study CZOL446H2301E1 but prior to randomization in Study CZOL446H2301E2.
4. Any prior use of PTH for more than 1 month during Study CZOL446H2301E1 and during the period after completion of Study CZOL446H2301E1 but prior to randomization in Study CZOL446H2301E2.
5. Use of systemic corticosteroids (oral or i.v.) at an average dose of greater than or equal to 7.5 mg per day of oral prednisone or equivalent for a period of three months just prior to randomization into Study CZOL446H2301E2. Note: Use of corticosteroids in forms such as topical creams, nasal or inhaled formulations or those injected locally (intra-articularly) are NOT exclusionary.
6. Any use of anabolic steroids or growth hormone for more than 3 months just prior to randomization into Study CZOL446H2301E2.
7. Any prior use of strontium (all formulations).
8. Any use of sodium fluoride for osteoporosis during Study CZOL446H2301E1 and during the period after completion of Study CZOL446H2301E1 but prior to randomization in Study CZOL446H2301E2.
9. Serum calcium less than 8 mg/dL (2.0 mmol/L) at Visit 11 in Study CZOL446H2301E1 or at a subsequent pre-dose laboratory test prior to randomization in Study CZOL446H2301E2.
10. Serum calcium greater than 11.0 mg/dL (2.75 mmol/L) at Visit 11 in Study CZOL446H2301E1 or at a subsequent pre-dose laboratory test prior to randomization in Study CZOL446H2301E2.
11. Active primary hyperparathyroidism.
12. Surgery to the thyroid or parathyroids resulting in partial or complete hypoparathyroidism.
13. Uncontrolled seizure disorders associated with falls.
14. Bilateral hip replacement or bilateral hip surgery with implantation of an appliance during the Study CZOL446H2301E1.
15. Patients with a new diagnosis or active treatment for cancer with the exception of treated non-melanoma skin cancer during the course of Study CZOL446H2301E1.
16. Multiple myeloma or Paget’s disease diagnosed or discovered during Study CZOL446H2301E1.
17. Active iritis or uveitis at the time of randomization.
18. History of diabetic nephropathy or retinopathy or uncontrolled diabetes (e.g. patients with a history of HbA1c > 10%).
19. A calculated creatinine clearance less than 30.0 mL/min (0.5 mL/sec) or urine dipstick greater than 2+ protein without evidence of contamination or bacteriuria at Visit 11 (final Study CZOL446H2301E1 study visit) or at a subsequent pre-dose laboratory test prior to randomization in Study CZOL446H2301E2.
20. History of hypersensitivity to bisphosphonates or any serious adverse reaction to the study drug during Study CZOL446H2301E1.
21. Use of other investigational drugs within 3 months prior to randomization in Study CZOL446H2301E2.
22. Any medical or psychiatric condition which, in the Investigator’s opinion, would preclude the participant from adhering to the Protocol or completing the trial per protocol.
23. Patients with a decrease in bone mineral density at the total hip of greater than 10% from baseline in Study CZOL446H2301E1 to any post-randomization DXA scan in Study CZOL446H2301E1.
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change in BMD of the total hip at Year 9 relative to Year 6 compared to Z6P3 patients |
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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 | Yes |
E.7.1.3.1 | Other trial type description |
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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 | No |
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.8.3 |
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.8.5 | The trial involves multiple Member States | Yes |
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 | Yes |
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 end of the trial will be completed when all Visit 15 study procedures have been done by the last patient |
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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 | |
E.8.9.2 | In all countries concerned by the trial years | 4 |