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 | 17.0 |
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 |
Primary Objective for the 12 Month Base Study: To assess the effect of L-001037536 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on lumbar spine BMD compared to placebo over 12 months.
Primary Objective for the Extension Study to 24 Months: To assess the effect of L 001037536 3 mg weekly, 10 mg weekly, 25 mg weekly, and 50 mg weekly on lumbar spine BMD compared to placebo over 24 months. |
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E.2.2 | Secondary objectives of the trial |
Secondary Objectives for the 12 Month Base Study and 24 Month Extension: To assess the effect of L-001037536 3 mg-, 10 mg-, 25 mg-, and 50 mg- weekly on (1) total hip, femoral neck, trochanter, total body, and distal forearm BMD compared to placebo (2) biochemical indices of bone resorption (u-NTx, s-CTx, u-DPyr) compared to placebo. (3) biochemical indices of bone formation (s-BSAP, s-P1NP) compared to placebo. (4) indices of calcium and mineral homeostasis (s-calcium, s-phosphorus, s PTH, s-1,25-dihydroxyvitamin D, 24 h urine calcium) compared to placebo. (5) safety and tolerability compared to placebo. (6) To identify the optimal dosing regimen of L-001037536 based on each regimen’s overall effect on BMD, biochemical markers, and safety. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Postmenopausal female (> 5 years) between 45-85 years old.
T-score at the hip (femoral neck, trochanter or total) or lumbar spine <-2.0, but not < -3.5.
The patient has spinal anatomy suitable for dual-energy x-ray absorptiometry (DXA) of the lumbar spine with no evidence of vertebral fractures in at least 3 vertebrae in the L1 to L4 region on baseline spine films. (Significant scoliosis, bony trauma, degenerative joint disease, and sequelae of orthopedic procedures that result in anatomy that is unsuitable for accurate bone densitometry must be absent from the lumbar spine.) The patient has a 25-hydroxyvitamin D level ≥15 ng/dL. If the level is ≥ 9 and < 15 ng/dL, she may enter if her alkaline phosphatase and PTH levels are normal. The patient has no evidence of a metabolic bone disorder other than osteopenia or osteoporosis. The patient understands the procedures of the study, has been informed of potential alternative treatments for osteoporosis, and is willing to give written informed consent for participation. The patient agrees not to use medications for the treatment of osteoporosis (except as provided through this study) for the duration of her participation in the trial.
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E.4 | Principal exclusion criteria |
The patient has a BMD T-score at the spine or hip (femoral neck, trochanter, or total) <-3.5. The patient has a history of prior hip, spine, or other fragility fracture since menopause (UNLESS the patient is unwilling to take, or is ineligible for, other osteoporosis therapy [bisphosphonates or PTH]). The patient has received any agents with action on bone including the following: (a) anabolic steroids or glucocorticoids (≥ 5 mg/day prednisone or equivalent) for more than 2 weeks in the prior 6 months, (b) bisphosphonates (any oral use within the past 6 months; ≥ 2 weeks use within the past 12 months; or > 2 months use at any time), or any I.V. bisphosphonates, (c) cyclosporin for more than 2 weeks within the prior 6 months, (d) fluoride treatment at a dose greater than 1 mg/day for more than 2 weeks at any time, (e) strontium (at any time) (f) PTH within 12 months, (g) current use of phenytoin, chemotherapy, or heparin, or (h) use of growth hormone at any time. The patient has used estrogen ± progestin, raloxifene or other SERM, tamoxifen, tibolone, or an aromatase inhibitor within the prior 6 months or calcitonin within the prior 30 days. (Note: Vaginal estrogen creams used topically ≤ twice weekly will be permitted). The patient is currently taking Vitamin A (excluding beta carotene) > 10,000 IU daily or Vitamin D > 5,000 IU daily and not willing to discontinue this dose during the study. The patient has primary parathyroid disease with an elevated PTH or in conjunction with serum calcium greater than the upper limit of normal. (Note: patients with a history of primary hyperparathyroidism and with curative parathyroidectomy ≥ 2 years are not excluded). The patient has a TSH < 0.1 ng/dL. The patient has hypocalcemia as defined as serum calcium <8.5 ng/dL, when corrected for albumin, or evidence of secondary hyperparathyroidism. Patients with (a) a history of marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a QTc interval >450), or (b) additional risk factors for Torsades de Pointes (e.g. heart failure, hypokalemia, family history of Long QT Syndrome), or (c) concomitant use of medications that prolong the QT/QTc interval (e.g. quinidine, procainamide, disopyramide, tricyclic antidepressants, phenothiazines, amiodarone or sotalol) will be excluded. The patient has significant clinical or laboratory abnormalities at the screening visit for the study that, in the opinion of the investigator, could complicate interpretation of the study results or pose additional risk to the patient. The patient has a significant, unexplained laboratory abnormality. The patient has cancer or had a diagnosis of any malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer The patient is, in the opinion of the investigator, mentally or legally incapacitated such that informed consent cannot be obtained or the patient cannot read or comprehend the written material. The patient has participated in an investigational drug study within the past 30 days. The patient is currently a user of any illicit drug and/or has a history of alcohol abuse. The patient demonstrates noncompliance in following the procedures required in the study.
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E.5 End points |
E.5.1 | Primary end point(s) |
Percent change from baseline in lumbar spine BMD |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.6.13.1 | Other scope of the trial description |
5-year open label (50 mg odanacatib once weekly) safety & efficacy extension to the original study. |
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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 | No |
E.8.1.7.1 | Other trial design description |
Originally double blind, extension is open label, not randomised. Same treatment for all subjects. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.3.1 | Comparator description |
Originally placebo, active treatment for all subjects in the extension phase. |
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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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The date the last subject completes the final 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 | 4 |
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 | 6 |