E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Men and Postmenopausal Women with Low Bone Mass and a Recent Pertrochanteric Hip Fracture. |
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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 |
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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 |
Test the hypothesis that teriparatide 20 μg subcutaneously once daily is superior to risedronate 35 mg orally once weekly in the change from baseline to 18 months of lumbar spine BMD in men and postmenopausal women with low bone mass and a recent pertrochanteric hip fracture, as measured by dual energy x-ray absorptiometry (DXA). |
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E.2.2 | Secondary objectives of the trial |
To test the hypothesis that teriparatide is superior to risedronate in the change from baseline in lumbar spine areal BMD measured by DXA, at 26 weeks and 12 months of treatment. To compare the effects of teriparatide with those of risedronate on areal BMD measured by DXA at the femoral neck and total hip of the non-fractured limb, at 26 weeks, 12 months, and 18 months of treatment. To compare the effects of teriparatide with those of risedronate on patient self-reported physical function and health status at 6, 12, 18, and 26 weeks from randomization. To compare the effects of teriparatide with those of risedronate on patient self-reported pain at the hip at 6, 12, 18, and 26 weeks from randomization. To compare the effects of teriparatide with those of risedronate on patient functional activities at 6, 12, 18, and 26 weeks from randomization. To evaluate safety as determined by vital signs, clinical laboratory data, and reports of treatment-emergent adverse events (TEAEs). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Men and postmenopausal women aged 50 to 78 years inclusive at the time of entry into the trial. In women, last menstrual period or bilateral oophorectomy has to occur at least 2 years prior to entry into the trial. Subjects must be able to walk unassisted prior to the fracture, and free of severe or chronically disabling conditions, including dementia and gait problems. Have a life expectancy of at least 3 years. AP lumbar spine (L-1 through L-4) BMD and/or femoral neck BMD and/or total hip BMD measurement of the contra lateral hip at least 2.0 SDs below the average bone mass for young women and men. Patient has sustained a unilateral, fracture of the trochanteric region caused by a low-energy injury. Fracture is treated with an intramedular hip nail or a sliding compression hip screw with or without a trochanteric stabilizing plate. Able to satisfactorily use a pen-type injection delivery system in the opinion of the investigator and willing to be trained on use of the pen-injector and willing to use the pen-injector on a daily basis, or is willing to receive daily subcutaneous injections from a care partner who has been trained to use the pen injector. |
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E.4 | Principal exclusion criteria |
Clinically significant abnormal laboratory values (as defined by the investigator) of total alkaline phosphatase and/or abnormally elevated serum total calcium levels at the screening visit. Abnormally elevated values of serum intact PTH(1-84) at the screening visit. Severe vitamin D deficiency defined at 25-hydroxy-vitamin D levels. Abnormally elevated or decreased fT4 levels at the screening visit. Patients with sub-clinical hyperthyroidism or hypothyroidism, defined as abnormally low or high serum values of TSH respectively, with normal or slightly low fT4 values (mild overt hypothyroidism), are eligible to participate in the study. History of unresolved skeletal diseases that affect bone metabolism including renal osteodystrophy, osteomalacia, any secondary causes of osteoporosis, hyperparathyroidism (uncorrected), and intestinal malabsorption. Increased baseline risk of osteosarcoma; this includes patients with Pagets 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 Pagets disease, an unexplained elevation of this enzyme activity will also be exclusionary. History of a malignant neoplasm in the 5 years prior to Visit 1, with the exception of superficial basal cell carcinoma or squamous cell carcinoma of the skin that has been definitively treated. Patients with carcinoma in situ of the uterine cervix treated definitively more than 1 year prior to entry into the study may enter the study. History of symptomatic nephro- or urolithiasis in the year prior to Visit 1. Active liver disease or clinical jaundice. Significantly impaired renal function. History of bone marrow or solid organ transplantation. Bilateral hip fractures. Previous fracture(s) or bone surgery in the currently fractured hip. Soft tissue infection at the operation site. Patient treated with hip prosthetic replacement techniques. Patient treated with external fixation of the petrochantic fracture or with ordinary Ender nails or 2D bent nails. Patient treated with bone grafting or osteotomies. Treatment with augmentation using any type of degradable cement, hydroxyapatite-coated implants or with non-invasive interventiones with ultrasound, magnetic field/electrical stimulation. Local or systemic treatment with bone morphogenic proteins (BMPs) or any other growth factor. Polytrauma patients and patients with fractures at more than one site. Treatment with fluoride, strontium ranelate, IV/oral bisphosphonates, SERM, calcitonin, estrogen antagonists, tibolone. Prior treatment with PTH, teriparatide or risedronate or excipients of teriparatide or to any other form of PTH or PTH analogue. Presence of any condition which contraindicates risedronate therapy. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change in actual AP lumbar spine BMD as determined by areal DXA from baseline to 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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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 |
6 mesi in ``double dummy``, dal 6 al 18 mese in aperto |
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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.8.3 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 30 |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |