E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
treatment males with glucocorticoid-induced osteoporosis GIOP |
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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 test the hypothesis that teriparatide 20 956;g subcutaneously once daily is superior to risedronate 35 mg orally once weekly in the change from baseline to 18 months of lumbar spine volumetric trabecular bone mineral density in males with glucocorticoid-induced osteoporosis. All patients will receive elemental calcium 1000 mg orally once daily and vitamin D 800-1200 IU orally once daily. |
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E.2.2 | Secondary objectives of the trial |
to test the hypothesis that Teriparatide is superior to risedronate in several aspects -The improvement of the lumbar spine volumetric trabecular and integral BMD as measured by QCT at 6 months and at 6 and 18 months of treatment.-The improvement of the 3D microstructural variables as measured by HR-QCT in the T-12 at 6 and 18 months.-The improvement of the biomechanical variables evaluated by a finite element analysis in the T-12 at 6 and 18 months of treatment.To compare the effects of both treatments on areal BMD response at the lumbar spine, femoral neck, and total hip, at 18 months of treatment, and on biochemical markers of bone turnover including P1NP and serum type -CTx at at 3, 6 and 18 months of treatment. to evaluate safety. to examine the relationship between biochemical markers of bone turnover and the high-resolution quantitative computerized tomography variables, including finite element analysis, at 6 and 18 months of therapy with teriparatide or risedronat |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Ambulatory men 25 years of age and older presenting to Visit 1 with a BMD of at least 1.5 SD below the corresponding normal young adult men average BMD T score of 1.5 or lower , at any of the following regions of interest total hip, femoral neck, or lumbar spine. Have received glucocorticoid therapy at an average dose of at least 5.0 mg/day of prednisone or its equivalent for a minimum of 3 consecutive months immediately preceding screening Visit 1 , as determined by medical history rare exceptions may be enrolled if previously approved A minimum of 2 lumbar vertebrae in the L-1 through L-3 region must be evaluable by quantitative computerized tomography. Normal or clinically insignificant abnormal laboratory values including serum calcium, PTH 1 84 , and 25 hydroxyvitamin D concentrations, and alkaline phosphatase activity |
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E.4 | Principal exclusion criteria |
Presence of a mild, moderate or severe spinal fracture in both T-12 and L-1, as determined by the central reading facility using the semiquantitative technique by Genant et al. 1993 . Patients with a normal vertebral body height i.e.; vertebral height reduction 20 either at T-12 or L-1 are eligible for the study see section 6.1.2.2 . Abnormal albumin-corrected serum calcium levels as determined by the investigators site laboratory. History of unresolved skeletal diseases that affect bone metabolism other than glucocorticoid-induced osteoporosis. History of malignant neoplasms in the 5 years prior to Visit 2, with the exception of superficial basal cell or squamous cell carcinomas of the skin that have been definitively treated. Increased baseline risk of osteosarcoma; this includes patients with Paget s disease of the bone, previous primary skeletal malignancy, or skeletal exposure to therapeutic irradiation. As elevation of serum skeletal alkaline phosphatase activity may indicate the presence of Paget s disease, an unexplained elevation of this enzyme activity will also be exclusionary. History of symptomatic nephro- or urolithiasis in the year prior to Visit 2. Abnormal thyroid function not corrected by therapy. Normal thyroid function may be documented by a normal serum thyroid-stimulating hormone TSH value during the screening phase or a combination of clinical and biochemical parameters which, in the judgment of the investigator and the Lilly clinical research physician, sufficiently establishes the presence of normal thyroid function. Significantly impaired renal function as defined by measured or calculated endogenous creatinine clearance 30 mL/min using the Cockcroft-Gault formula for creatinine clearance. History of excessive consumption of alcohol or abuse of drugs in the 1 year prior to Visit 2, in the opinion of the investigator. Poor medical condition or psychiatric risk for treatment with an investigational drug, in the opinion of the investigator. History of bone marrow or solid organ transplantation. Treatment with any other drug except corticosteroids in the 6 months prior to Visit 2, if that drug is believed by the investigator to significantly affect bone or calcium metabolism. Treatment with - Fluoride at therapeutic doses 20 mg/day for more than 3 months in the 2 years prior to Visit 2, or for more than a total of 2 years, or at any dosages within the 6 months prior to Visit 2. Previous or current use of fluoridated water or topical dental fluoride treatment is permitted - Strontium ranelate for any duration - Intravenous bisphosphonates, at any dose, within the 12 months prior to Visit 2. Previous treatment for any duration with calcitonin, oral bisphosphonates or active vitamin D3 analogues is allowed, but it should be stopped by the randomization visit. Have received treatment within the last 30 days with a drug not including study drug that has not received regulatory approval for any indication at the time of study entry. Known allergy to teriparatide or risedronate, any diluents or excipients of teriparatide, or to any other form of PTH or PTH analog. Presence of any condition which contraindicates risedronate therapy. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy measurement in this study is the change in actual lumbar spine volumetric trabecular BMD vBMD as determined by quantitative computerized tomography QCT from baseline to 18 months. For QCT of the spine L1-L3 will be scanned completely, slice thickness 3 mm, i.e.; 25-35 slices for a vertebral range of approximately 8-12 cm, 80 kV, and 140 mAs. |
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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 | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Information not present in EudraCT |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 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 | Information not present in EudraCT |
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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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 | 2 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |