E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Bone loss occurring around cementless hip prosthesis in postmenopausal women treated for primary hip osteoarthritis |
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MedDRA Classification |
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 is to demonstrate that a single dose of zoledronic acid reduces periprosthetic bone loss measured by DXA. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to demonstrate that the treatment can enhance biologic incorporation of cementless hip prostheses as shown by reduced prosthetic migration measured by RSA (radiostereometry), to demonstrate that enhanced incorporation of the hip prostheses following the therapy lead to faster functional recovery and better subjective outcome of the procedure, and to demonstrate that the treatment suppresses biochemical markers of bone resorption.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Key Inclusion Criteria: - Degenerative hip osteoarthritis as the indication for hip replacement - Postmenopausal female patient - Age of at least 20 years - Signed Informed Consent
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E.4 | Principal exclusion criteria |
Exclusion Criteria: - Evidence of secondary osteoporosis - Clinical or laboratory evidence of hepatic or renal disease - Disorders of parathyroid function, or D-vitamin metabolism - History of malignancy, radiotherapy, or chemotherapy for malignancy (except for basal cell carcinoma of the skin) within the past 5 years - No metastatic cancer or cancer diagnosed less than 2 years ago where treatment is still ongoing - Administration for more than 7 days of drugs, which may interfere with bone metabolism: • cumulative dose of 500 mg of prednisone or equivalent within the last 6 months • calcitonin within the last 6 months • bisphosphonates for 30 days or more within the last 12 months • bone therapeutic doses of fluoride for 30 days or more within the last 24 months - Rheumatoid arthritis or any other inflammatory arthritis - History of osteogenesis imperfecta, multiple myeloma, or Paget’s disease - Active primary hyperparathyroidism - History of uveitis, iritis, or chronic conjunctivitis - History of retinopathy or nephropathy, especially in the presence of uncontrollable IDDM (Hb1AC > 10%) - AST or ALT > 2X the upper limit of normal - ALP > 1.5X the upper limit of normal - Serum creatine > 2 mg/dl - Creatine clearance < 40 ml/min - Serum calcium 11.0 mg/dL and < 8mg/dL - Serum 25(OH)D < 15 ng/ml - In subjects with HIV must have a plasma HIV-1 RNA level of < 5000, a CD4+ count of > 100 cells/mm3m and be receiving stable ART for a minimum of 12 weeks prior study entry, with no plan at study entry to significantly alter ART - Allergy to zoledronic acid - Severe dental problems or current dental infections or with recent or impending dental surgery within three months of dosing
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E.5 End points |
E.5.1 | Primary end point(s) |
As the primary radiologic endpoint, to detect any difference between the patient groups in prosthetic incorporation with the surrounding bone, sequential DXA measurements will be performed to delineate the effect of zoledronic acid therapy in prevention of periprosthetic bone mineral loss at each follow-up visit. |
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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 | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
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 | 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
| 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 | Information not present in EudraCT |
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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If necessary for the safety or any scientific reasons, the trial will be ended by the combined decision of the PI and local ethical committee. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |