E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Postmenopausal Osteoporosis |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10031285 |
E.1.2 | Term | Osteoporosis postmenopausal |
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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 characterize percent change from baseline in bone mineral density (BMD) at L1-L4 axial lumbar spine after 6 months of once daily treatment of 5 mg tablets of PTH(1-31)NH2. |
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E.2.2 | Secondary objectives of the trial |
To characterize percent change from baseline in bone mineral density (BMD) at L1-L4 axial lumbar spine after 6 months of once daily treatment of matching placebo tablets.
To demonstrate a statistically significant increase in BMD using bone mineral density measurements (DXA) in L1-L4 lumbar spine after 24 weeks of treatment with oral rhPTH(1-31)NH2 compared to baseline.
To demonstrate a biological response using bone mineral density measurements (DXA) in the total hip, trochanter and femoral neck in after 24 weeks of treatment with oral rhPTH(1-31)NH2 compared to baseline.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Informed consent: Willing and able to sign written informed consent. • Ambulatory postmenopausal women in good health. Menopausal status: Subject should be at least 5 years postmenopausal which can be >5 years of spontaneous amenorrhea or >5 years postsurgical bilateral oophorectomy. Use follicle stimulation hormone (FSH) levels >40 mIU/mL to confirm surgical postmenopausal status where bilateral oophorectomy status is uncertain. • Age 45 years - 80 years • BMD values: • Diagnosis of osteoporosis on the basis of an axial lumbar spine, femoral neck or total hip BMD which is below the mean for premenopausal women by a magnitude of at least 2.5 SD or 2.0 SD, if there is a documented history of a vertebral fragility fracture. T-Score Values GE-Lunar BMD Values Hologic BMD Values T-Score L1-L4 Total Hip Femoral Neck L1-L4 Total Hip Femoral Neck -2.0 0.958 0.768 0.808 0.827 0.702 0.629 -2.5 0.903 0.708 0.753 0.772 0.642 0.574
• Suitable vertebrae: Two or more vertebra in the range of L1 to L4 that are suitable for BMD measurement by DXA. • No clinically significant abnormal findings in the medical history or physical examination o Negative screen for Hepatitis B and C, HIV and drugs of abuse at screening. • Laboratory values: o Total serum Ca, albumin-adjusted Ca, P, and Mg++ within normal range. o No clinically significant abnormal laboratory values at the screening assessment.
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E.4 | Principal exclusion criteria |
• BMI: BMI ≤33kg/m2 • Illnesses: • Liver function: Known hepatic or biliary abnormalities including Gilbert's syndrome. • Abnormal Liver function tests (ALT, AST, GGT, alkaline phosphatase, total bilirubin). • Medical illness: Presence of acute or chronic illness or history of chronic illness which, in the judgment of the Investigator, makes participation in the study medically inappropriate. • History of clinically significant cardiovascular disease and/or postural hypotension. • QT/QTc prolongation: A marked baseline prolongation of QT/QTc interval (e.g., QTc interval > 450 msec on the Screeing ECG. • Torsades des Pointes: A history of risk factors for Torsades de Pointes(e.g., heart failure, hypokalemia, family history of Long QT Syndrome). • History of pancreatitis, osteosarcoma or kidney stones. • Uncontrolled hypertension, significant gastrointestinal abnormalities, uncontrolled diabetes mellitus, any psychotic mental illness, uncorrected endocrine dysfunction, or significantly impaired respiratory or renal function. • Medical conditions which might alter bone metabolism, including: hyperparathyroidism, hypoparathyroidism, hyperthyroidism, hypothyroidism, Paget's disease, myeloma, malabsorption, Cushing's syndrome, hypocalcemia, hypercalcemia, hypophosphatemia, hyperphosphatemia, hypomagnesemia, hypermagnesemia, osteopetrosis, osteomalacia, rheumatoid arthritis and recent (within one year) history of non-traumatic fracture or prolonged bed rest. • History of musculoskeletal disease. However, subjects with conditions such as fibromyalgia, osteoarthritis, and degenerative disc disease may be enrolled at the discretion of the Investigator and Medical Monitor. • History of cancer within 5 years of enrollment other than basal cell carcinoma. • History of surgery within 60 days of enrollment. • Evidence of alcohol or substance abuse that the Investigator believes would interfere with understanding or completing the study. • Electrocardiogram: Any clinically relevant abnormality identified on the 12-lead surface electrocardiogram (ECG). • Laboratory Findings: Albumin-adjusted serum calcium greater or less than the normal reference range of the analytical laboratory. • Urine calcium greater than the normal reference range of the analytical laboratory • PTH(1-84) greater than the normal reference range of the analytical laboratory. • Abnormal Alkaline Phosphatase • Vitamin D: Vitamin D insufficiency defined as a 25 hydroxyvitamin D level <15 ng/mL. • DXA: Any condition or disease that may interfere with the ability to have a DXA scan or to evaluate a DXA scan, for example, severe osteoarthritis of the spine, spinal fusion, pedicle screws, history of vertebroplasty, or degenerative disease that results in insufficient number of evaluable lumbar vertebrae, or more than 1 lumbar vertebral fracture in L1 through L4. • More than 4 vertebral fractures in T4 through L4 per prior medical history. • Bilateral hip replacements.
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E.5 End points |
E.5.1 | Primary end point(s) |
Bone Mineral Density, Bone Resorption Marker, Bone Formation Marker |
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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 | Yes |
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 | Yes |
E.8.1.7.1 | Other trial design description |
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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 | 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.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 5 |
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 | 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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Last patient out is 31st December 2011 |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |