E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Postmenopausal osteoporosis |
|
E.1.1.1 | Medical condition in easily understood language |
Postmenopausal osteoporosis |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10031285 |
E.1.2 | Term | Osteoporosis postmenopausal |
E.1.2 | System Organ Class | 10028395 - Musculoskeletal and connective tissue disorders |
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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 the study is to evaluate the effect of denosumab 60 mg every 6 months (Q6M) compared with Actonel® 150mg monthly (QM) on total hip Bone Mineral Density (BMD) at 12 months in postmenopausal women transitioning from previous alendronate therapy. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effects of denosumab 60 mg Q6M and Actonel® 150 mg QM on:
• CTX (in a subset of subjects) at 1 month
• BMD at the femoral neck at 12 months
• BMD at the lumbar spine at 12 months |
|
E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
CTX sub-study (08 June 2009)
Serum type 1 CTX samples will be collected at month 1 and month 6 in a subset of subjects (planned total of approximately 250 subjects). |
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E.3 | Principal inclusion criteria |
Subjects will meet the following inclusion criteria prior to enrolment:
- Ambulatory, postmenopausal women (based on medical history) aged 55 years or older at screening:
• Postmenopause will be defined as no vaginal bleeding or spotting for at least 12 months
• If the subject is < 60 years old and there is uncertainty regarding menopausal status, confirmation of serum FSH (≥ 50 mIU/mL) and serum estradiol (≤ 20 pg/mL) must be obtained
- Have received their first prescription of daily or weekly alendronate therapy, for the treatment for postmenopausal osteoporosis at least 1 month prior to screening. Use of raloxifene, calcitonin prior to alendronate treatment will be allowed. Prior and current use of vitamin D and calcium will be allowed.
• Hormone replacement therapy (e.g. estrogen use for mitigation of
menopausal symptoms) will be allowed.
- Subject has demonstrated 1 of the following:
• Has stopped oral alendronate therapy (is denoted as non-persistent) before the screening visit.
• Is still taking oral alendronate therapy but demonstrates low adherence to therapy assessed by a score of less than 6 on the Osteoporosis Specific Morisky Medication Adherence Scale (OS-MMAS)
- Provide signed informed consent before any study-specific procedures are conducted |
|
E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria are not eligible for participation in the study:
- Any prior or current use of medications prescribed for osteoporosis treatment other than:
• oral daily or weekly alendronate
• Hormone replacement therapy (e.g. estrogen use to mitigate
menopausal symptoms)
• calcium and vitamin D
• prior use of raloxifene and calcitonin before alendronate therapy was initiated will
be allowed. Use of these therapies must have stopped prior to initiating oral
alendronate and their current use is not allowed
- Hypersensitivity to Actonel® or other constituents of Actonel® tablets
- Contraindicated or poorly tolerant of alendronate therapy; contraindications for alendronate therapy include:
• Abnormalities of the esophagus which delay esophageal emptying such as stricture or achalasia
• Inability to stand or sit upright for at least 30 minutes
- Active gastric or duodenal ulcer; history of significant gastrointestinal bleed requiring hospitalization or transfusion, or dyspepsia or gastro esophageal reflux disease that is uncontrolled by medication
- Known sensitivity to mammalian cell derived drug products
- Known intolerance to calcium supplements
- Malignancy within the last 5 years (except cervical carcinoma in situ or basal cell carcinoma
- Vitamin D deficiency [25(OH) vitamin D level < 20 ng/mL (< 49.9 nmol/L)] - Repletion will be allowed and subjects may be re-screened
- Current hypo- or hypercalcemia based on the central laboratory reference ranges
- Uncontrolled hyper- or hypothyroidism (stable on antithyroid therapy or post-ablation is allowed, if the central laboratory TSH is within the normal range)
- Hyper- or hypoparathyroidism per the central laboratory reference ranges
- Any metabolic bone disease, eg, osteomalacia or osteogenesis imperfecta, Paget’s
disease of bone, that may interfere with the interpretation of the findings, and other
disorders including
• Significantly impaired renal function as determined by a derived glomerular
filtration rate (GFR) (using the Modification of Diet in Renal Disease [MDRD]
formula) of ≤ 30 mL/min/1.73 m2 calculated by the central laboratory.
• Clinically determined malabsorption syndrome that may result from disorders such as celiac disease, gastric bypass surgery, bowel
resection, uncontrolled diarrhea and steatorrhea.
• Elevated transaminases ≥ 2.0 x upper limits of normal (ULN)
- Height, weight or girth which may preclude accurate DXA measurements
- Fewer than 2 lumbar vertebrae (L1-L4) able to be evaluated by DXA
- Known to have tested positive for human immunodeficiency virus
- Previous participation in clinical trials with denosumab within the last 12 months (regardless of treatment)
- Any laboratory abnormality, physical or psychiatric disorder (including substance abuse in last 12 months) which, in the opinion of the investigator, will prevent the subject from giving written informed consent or completing the study or interfere with the interpretation of the study results
- Currently enrolled in or within 30 days of ending another investigational device or drug trial(s)
- Administration of any of the following treatments within 3 months of screening
• Tibolone
• Anabolic steroids or testosterone
• Glucocorticosteroids (≥ 5 mg prednisone equivalent per day for more than 10
days or a total cumulative dose of ≥ 50 mg) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percent change from baseline in BMD at the total hip |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
• Percent change from baseline in CTX (in subset of subjects)
• Percent change from baseline in BMD at the femoral neck
• Percent change from baseline in BMD at the lumbar spine |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Percent change from baseline in CTX (in subset of subjects) at 1 month
• Percent change from baseline in BMD at the femoral neck at 12 months
• Percent change from baseline in BMD at the lumbar spine at 12 months |
|
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) | 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 | 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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 73 |
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 | No |
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 |
European Union |
Australia |
Canada |
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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
|
End of study is defined as the date the last eligible subject completes the final study visit. |
|
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 | 11 |
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 | 11 |
E.8.9.2 | In all countries concerned by the trial days | 0 |