E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Postmenopausal osteoporosis /osteopenia |
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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 |
To evaluate the effect of denosumab compared to treatment with alendronate sodium (ALN) on percent change from baseline in bone mineral density (BMD) at the total hip as measured by dual energy X-ray absorptiometry (DXA) at 12 months in postmenopausal women. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effects of denosumab compared to treatment with ALN on: • Percent change from baseline in BMD at the distal 1/3 radius, hip trochanter, femoral neck, and lumbar spine as measured by DXA at 12 months. • Safety and tolerability as measured by evaluating adverse events, laboratory parameters, and vital signs over 12 months. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
-Ambulatory postmenopausal women based on medical history. -BMD values (g/cm2), assessed at the local site that correspond to T-score ≤ -2.0 at the lumbar spine OR total hip as follows: a) For the lumbar spine, the BMD values (g/cm2) must be ≤0.940 (GE lunar) or ≤0.827 (Hologic) b) For the total hip, the BMD values (g/cm2) must be ≤0.756 (GE lunar) or ≤0.698 (Hologic) -Provide the appropriate written informed consent before any study-specific procedure. |
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E.4 | Principal exclusion criteria |
-Any disorder that compromises the ability of the subject to give written informed consent and /or comply with study procedures -Evidence of any of the following: a) Hyper- or hypothyroidism b) Current hyper- or hypoparathyroidism c) Elevated transaminases d) Significantly impaired renal function as determined by serum creatinine ≥ 2.0 mg/dL e) Current hypo- or hypercalcemia based on the central laboratory reference ranges f) Active gastric or duodenal ulcer; history of significant gastrointestinal bleed requiring hospitalization or transfusion, or dyspepsia or gastroesophageal reflux disease that is uncontrolled by medication g) Rheumatoid Arthritis, Paget’s disease, Cushing’s disease, hyperprolactinemia, or cirrhosis of the liver h) Known to have tested positive for human immunodeficiency virus, hepatitis C virus, or hepatitis B surface antigen i) Malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5 years j) Any metabolic bone disease, eg, osteomalacia or osteogenesis imperfecta, which may interfere with the interpretation of the findings k) Malabsorption syndrome or any gastrointestinal disorders that are associated with malabsorption -Received any solid organ or bone marrow transplant. -Vitamin D deficiency (25(OH) vitamin D level < 12 ng/mL). -Any laboratory abnormality which, in the opinion of the investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results. -Contraindicated or poorly tolerant of ALN therapy. -Known sensitivity to mammalian cell derived drug products. -Known intolerance to calcium supplements. -Administration of intravenous bisphosphonate, or fluoride (except for dental treatment) or strontium ranelate. -Oral bisphosphonate treatment: • ≥ 3 months cumulatively in the past 2 years, OR • ≥ 1 month in the past year, OR • Any use during the 3-month period prior to randomization -PTH or PTH derivatives (eg, teriparatide) within the last year. -Administration of any of the following treatments within 3 months of randomization: a) Any SERM (eg, raloxifene) b) Tibolone c) Anabolic steroids or testosterone d) Glucocorticosteroids (≥ 5 mg prednisone equivalent per day for more than 10 days) e) Systemic (oral, transdermal, topical) hormone replacement therapy (local vaginal estrogen preparation will be allowed) f) Calcitonin g) Calcitriol or vitamin D derivatives h) Other bone active drugs including anti-convulsives (except benzodiazepines) and heparin i) Chronic systemic ketoconazole, androgens, ACTH, cinacalcet, aluminum, lithium, protease inhibitors, methotrexate, gonadotropin-releasing hormone agonists -Height, weight or girth which may preclude accurate DXA measurements. -Less than 2 lumbar vertebrae (L1-L4) evaluable for DXA measurements. -Both hips not evaluable by DXA (eg, history of bilateral hip replacement or pins in both hips). -Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s), or subject is receiving other investigational agent. -Any physical or psychiatric disorder which, in the opinion of the investigator, will prevent the subject from completing the study or interfere with the interpretation of the study results. -Evidence of alcohol or substance-abuse within the last 12 months which the investigator believes would interfere with understanding or completing the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the percent change from baseline in total hip BMD at 12 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 | Information not present in EudraCT |
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) | 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.8.5 | 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 | 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 | 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 | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
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 | 7 |