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 24 weeks of once daily treatment of 5 mg tablets of rhPTH(1 31)NH2. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability after 24 wks of once daily (SID) treatment (treat.) of 5 mg tablets (tabs) of rhPTH(1-31)NH2;to characterize % change from baseline (BL) in BMD at L1-L4 axial lumbar spine after 24 wks of SID treat. of matching placebo tabs/of open label Forsteo SC injection;to demonstrate a statistically significant increase in BMD using DXA in L1-L4 lumbar spine after 24 wks of treat. with rhPTH(1-31)NH2 tabs compared to BL;to evaluate the change in BMD using DXA in the total hip,trochanter and femoral neck after 24 wks of treat. with rhPTH(1-31)NH2 tabs/ with open label Forsteo SC injection compared to BL; to characterize % change from BL in -CrossLaps and total PINP as markers for bone turnover after 4 wks, 12 wks, and 24 wks of SID treat. with 5 mg rhPTH(1-31)NH2 tabs; to characterize PK profile of 5 mg rhPTH(1-31)NH2 tabs after the first dose and at the end of treat.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Informed Consent: Provide written informed consent before initiation of any study related procedures. •Ambulatory postmenopausal women in good health. Menopausal status: Patient 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 (x-ray) history of a vertebral fragility fracture. •Suitable Vertebrae: Two or more vertebrae 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. - Negative screen for Hepatitis B and C, HIV and drugs of abuse at screening. •Laboratory Values: - Total serum Ca, albumin-adjusted Ca, P, and Mg++ within normal range. - No clinically significant abnormal laboratory values at the screening assessment.
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E.4 | Principal exclusion criteria |
•BMI ≥33 kg/m2 •Illnesses: - Liver function: Known hepatic or biliary abnormalities including Gilbert's syndrome. - Clinically significant abnormal liver function tests (ALT, AST, GGT, alkaline phosphatase, total bilirubin). - Abnormal kidney function tests: Creatinine clearance ≤30 ml/min; urinary calcium/creatinine ratio greater than 1.1 mmol/mmol on second morning voided specimen; or serum creatinine concentration exceeding 2 mg per deciliter (177 μmol per liter - 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 pancreatitis, osteosarcoma, gout, or kidney stones (calcium oxalate or calcium phosphate). - 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, untreated hyperthyroidism, untreated 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, patients 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 and carcinoma in situ. •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 screening ECG). - Torsades des Pointes: A history of risk factors for Torsades de Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome). •Electrocardiogram: Any clinically relevant abnormality identified on the 12-lead surface electrocardiogram (ECG). •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. •Laboratory Findings: - Albumin-adjusted serum calcium greater or less than 10% of the normal reference range of the analytical laboratory. - Urine calcium greater than the normal reference range of the 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, 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. - Bilateral hip replacements. •Contraindicated Medications: Contraindicated medications are defined in Table 4 2. •Osteosarcoma Risk: Patients at increased risk of osteosarcoma such as those with Paget’s disease of bone or any prior external beam or implant radiation therapy involving the skeleton. •Contraindications: Contraindications to therapy with teriparatide, calcium or Vitamin D. •Interfering Medications: Vitamin A in excess of 10,000 IU per day, heparin, lithium, or anticonvulsant medications including primidone, phenobarbital, phenytoin, and carbamazepine. •Investigational Drug Exposure: Administration of any investigation drug within 90 days preceding the first dose of study drug.
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change from baseline in the axial lumbar spine BMD values over a 24 week period. |
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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 | Yes |
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 | 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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 3 |
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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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 | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |