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 | 7.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10031285 |
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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 determine the efficacy of a two-consecutive-day, monthly dosing regimen (75mg on two consecutive days, monthly) of risedronate compared to a daily dosing regimen (5mg daily) of risedronate, by demonstrating the non-inferiority of the two-consecutive day, monthly regimen to the daily regimen assessed by percent change from baseline in lumbar spine bone mineral density (BMD) at 12 months in women with postmenopausal osteoporosis (PMO). |
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E.2.2 | Secondary objectives of the trial |
- % change from baseline in lumbar spine BMD at months 6 and 24. - % of responders in lumbar spine BMD) at months 12 and 24. - % change from baseline in total proximal femur, femoral neck, and trochanter BMD at months 6, 12 and 24. - % Change from baseline in urine NTX and serum BAP at months 3, 6, 12 and 24 in all subjects. - Number of subjects with at least one new vertebral body fracture at months 12 and 24. - Change from baseline in patient reported outcomes at months 12 and 24. - Safety of the 2-day monthly regimen of risedronate, compared to the daily regimen using: assessment of clinical laboratory values, vital signs, clinical fractures, adverse event profiles, and bone histomorphometry. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- Female, ambulatory, age 50 years and older - Postmenopausal > or = 5 years without menses (natural or surgical). FSH and estradiol will be evaluated for any subject <65 years of age, who has undergone hysterectomy without bilateral oophorectomy, to ensure the subject is postmenopausal. Such subjects must have serum FSH = 40 mIU/mL and estradiol = 20 pg/mL - In general good health as determined by medical history, physical examination, and laboratory tests; - Has at least 3 evaluable lumbar spine vertebral bodies (L1-L4), namely without fracture or degenerative disease; - Meets one of the following lumbar spine BMD criteria: a) Lumbar spine BMD (L1-L4) that is <0.772g/cm2 (Hologic) or <0.880g/cm2 (Lunar), corresponding to a BMD more than 2.5 standard deviations (SD) below the young adult female mean value, or b) Lumbar spine BMD (L1-L4) that is <0.827g/cm2 (Hologic) or <0.94g/cm2 (Lunar), corresponding to a BMD more than 2.0 SD below the young adult female mean value, and at least one prevalent vertebral body fracture (T4-L4): - Willing and able to provide written informed consent. |
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E.4 | Principal exclusion criteria |
- Any previous or ongoing clinically significant illness that, in the opinion of the investigator, could prevent the subject from completing the study; - Abuse of alcohol - Abuse of prescription or illicit drugs - Any condition or disease which may interfere with the evaluation of lumbar spine BMD - History of hyperparathyroidism, unless surgically corrected at least 12 months prior to enrollment. - Ongoing hyperthyroidism or osteomalacia at the time of enrollment - Any history of cancer within past 5 years, except for dermal squamous and basal cell carcinoma with documented 6 month remission. Subjects with a more recent history of successfully treated cervical carcinoma in situ will not be excluded provided there is documented 12 month remission. - BMI > 32kg/m2 - Any allergic or abnormal reaction to bisphosphonates - Use of any of the following medications within 3 months of starting investigational product or use of any of the following medications for more than 1 month at any time within 6 months prior to starting investigational product: a) Oral or parenteral glucocorticoids (> or = 5mg prednisone or equivalent/day); b) Anabolic steroids; c) Estrogens (oral, skin patch or gel), SERMs (raloxifene) or estrogen-related drugs eg tamoxifen, tibolone, except for low dose vaginal creams, tablets or insertable estrogen ring (< or = 0.2mg/day 17 Beta estradiol or < or = 1.5 mg/day estropipate d) Progestins e) Calcitonin f) Vit D supplements (>800 IU per day) g) Calcitriol, calcidiol, or alfacalcidol at any dose h) any bisphosphonate i) Fluoride (> or = 10 mg/day) j) Strontium and other bone active agents (isoflavones) k) Parathyroid hormone - Depot injection >10,000 IU vitamin D in the past 9 months - Markedly abnormal clinical laboratory parameters that are assessed as clinically significant by the investigator - Creatinine clearance of < 30mL/min - Hypocalcemia or hypercalcemia from any cause - Serum TSH value outside the normal laboratory range - Serum 25-hydroxy Vit D level <12ng/Ml (30nmol/L) - Participation in another clinical trial 30 days prior to enrollment - Demonstrated unlikely to comply with protocol requirements |
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E.5 End points |
E.5.1 | Primary end point(s) |
Demonstrating the non-inferiority of the two-consecutive day, monthly regimen to the daily regimen assessed by percent change from baseline in lumbar spine bone mineral density (BMD) at 12 months in women with postmenopausal osteoporosis (PMO). |
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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 | 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 | 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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End of the study is when the last patient has completed the Month 24 / Exit visit |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 10 |