E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Postmenopausal osteoporosis |
|
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 | 10031285 |
E.1.2 | Term | Osteoporosis postmenopausal |
|
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 change in total hip Bone Mineral Density (BMD) at 12 months in postmenopausal women transitioning from previous daily or weekly bisphosphonate therapy to denosumab 60 mg SC Q6M compared to that in subjects transitioning to ibandronate 150mg PO QM.
Safety Objectives: To evaluate safety and tolerability measured by evaluating adverse events, antidenosumab antibodies and laboratory analytes over 12 months.
|
|
E.2.2 | Secondary objectives of the trial |
To evaluate the effects of transitioning to denosumab 60 mg SC Q6M in comparison to transitioning to ibandronate 150 mg PO QM on
• Serum type 1 C-Telopeptide-1 (sCTX-1) levels at 1 month (in a subset of subjects) • 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 |
Bone turnover marker (BTM) sub-study (08 June 2009) Urine samples will be collected at month 1 and serum type I CTX samples will be collected at the Day 1, month 1 and month 6 visits in a subset of subjects (planned total of approximately 250 subjects).
|
|
E.3 | Principal inclusion criteria |
Subjects will meet all of the following inclusion criteria prior to enrollment:
Ambulatory, postmenopausal women (based on medical history) 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 55 – 59 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 − If the subject is 60 years or older, evaluation of FSH and estradiol levels is not needed to confirm menopausal status.
Have received their first prescription of daily or weekly bisphosphonate therapy at least 1 month prior to screening
May have received • raloxifene, calcitonin, prior to initiation of daily or weekly bisphosphonate therapy. • Up to 3 doses of monthly bisphosphonate prior to initiation of daily or weekly bisphophonate therapy • calcium, and vitamin D • Hormone replacement therapy (e.g. estrogen use for mitigation of menopausal symptoms)
Subject has: • Stopped daily or weekly bisphosphonate therapy (is denoted as non-persistent) at least one month before the screening visit, or • Demonstrated low adherence to therapy assessed by a score of less than 6 on the OS-MMAS
Screening BMD (g/cm2) values, at the lumbar spine OR total hip, that occur within the following ranges, based on the particular scanner that is used:
GE Lunar Hologic Lumbar spine 0.700 ≤BMD ≤0.940 0.607≤BMD ≤0.827 Total hip 0.504 ≤BMD ≤0.756 0.454 ≤BMD ≤0.698
Both the initial and the repeat DXA scan of the lumbar spine OR the total hip must meet the above eligibility criteria.
At least 2 lumbar vertebrae must be evaluable by DXA.
At least one hip must be evaluable by DXA (eg, no history of either bilateral hip replacement or pins in both hips)
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 disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures
• Current or prior use of medications prescribed for osteoporosis treatment other than oral daily or weekly bisphosphonate (with the exception of those listed in criteria 4.1.3)
Contraindicated to receive oral ibandronate 150 mg PO QM, including • Hypersensitivity to ibandronate 150 mg PO QM or other constituents of ibandronate 150 mg PO QM tablets • Abnormalities of the esophagus, which delay esophageal emptying such as stricture or achalasia • Inability to stand or sit upright for at least 60 minutes
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)
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
Evidence of any of the following per subject report, chart review or central laboratory result: • Significantly impaired renal function as determined by estimated Glomerular Filtration Rate less that 30mL/min/1.73 m2 determined by the central laboratory • Current hypo- or hypercalcemia based on the central laboratory reference ranges • Active gastric or duodenal ulcer; or any history of significant gastrointestinal bleed requiring hospitalization or transfusion • Known to have tested positive for human immunodeficiency virus, hepatitis C virus, or hepatitis B surface antigen • Malignancy (except fully resected cutaneous basal cell or squamous cell carcinoma, cervical or breast ductal carcinoma in situ) within the last 5 years • Any metabolic bone disease or secondary cause of bone loss that is not controlled and may interfere with the interpretation of the findings
Previous participation in clinical trials with denosumab 60 mg SC Q6M (regardless of treatment)
Received any solid organ or bone marrow transplant
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
Known sensitivity to mammalian cell derived drug products
Known intolerance to calcium supplements
Currently enrolled in or has not yet completed at least 1 month since ending other investigational device or drug trial(s)
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 |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Percent change from baseline in BMD at the total hip 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 | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
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 | 21 |
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 |
|
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 | 9 |
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 | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |