| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| 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 determine whether teriparatide, given as 20 mcg once daily by subcutaneous injection in postmenopausal women with osteoporosis who are at high risk for fracture, will be associated with an increase in skeletal plasma clearance of 99m Technetium methylene diphosphonate ( 99m Tc-MDP) measured from baseline to 18 months in the whole skeleton using nuclear scintigraphy. |
|
| E.2.2 | Secondary objectives of the trial |
Determine whether skeletal plasma clearance and skeletal uptake of 99m Tc-MDP measured in the whole skeleton and six subregions (skull, mandible, spine, pelvis, and upper and lower extremities) and quantitative visual score of focal and diffuse changes in the whole skeleton will demonstrate change at the following time points in response to teriparatide therapy:
o Increase from baseline to 3 months
o Increase from 3 months to 18 months
o Increase from baseline to 18 months
o Decrease from 18 months to 24 months
o Approach baseline value at 24 months
• To determine adverse experiences, laboratory variables, and other aspects of subject safety and tolerance of teriparatide. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
[1] Ambulatory, postmenopausal women.
[2] Aged 55 to 85 years, inclusive.
[3] Free of severe or chronically disabling conditions other than osteoporosis.
[4] Without language barrier, cooperative, expected to return for all follow-up visits, and who give informed consent before entering the study and after being informed of the medications and procedures to be used in this study.
[5] A minimum of either one moderate or two mild atraumatic vertebral fractures
• Atraumatic is defined as not caused by wound or injury that is severe enough to cause a fracture in otherwise healthy persons.
• Subjects with a history of traumatic fractures (for example, those caused by automobile accidents or falls from greater than standing height) are eligible only if they also have a minimum of one moderate or two mild atraumatic vertebral fractures and a minimum of seven evaluable nonfractured vertebrae.
• The initial fracture assessment and the determination of eligibility of the subject to be entered into the study will be made by the individual investigator.
[6] Total hip BMD or lumbar spine (L-1 to L-4) BMD measurement more than 2.5 standard deviations below the average bone mass for young, healthy women (T-score), as determined from the manufacturer’s database, only in subjects with fewer than two moderate fractures.
[7] Normal or clinically nonsignificant abnormal laboratory values (serum calcium, 25-hydroxyvitamin D, TSH, and urine calcium must be within normal limits at enrollment). |
|
| E.4 | Principal exclusion criteria |
[8] Fractures in areas of bone affected by diseases other than osteoporosis.
[9] Satisfactory baseline thoracic and lumbar spinal x-ray views cannot be obtained.
[10] Current or recent metabolic bone disorders other than postmenopausal osteoporosis or disease which affects bone metabolism.
[12] History of carcinoma in the previous 5 yrs or currently suspected carcinoma, with the exception of excised superficial lessions.
[13] Nephrolithiasis or urolithiasis in the 2 yrs prior to enrollment. Subjects with any history of nephro- or urolithiasis must have an appropriate radiology study within 6 calendar months prior to enrollment to document the absence of active disease.
[14] Current or recent sprue, inflammatory bowel disease, or malabsorption syndrome.
[15] Significantly impaired hepatic function or renal function.
[19] Treatment with androgens or other anabolic steroids in the 6 calendar months prior to enrollment.
[20] Treatment with calcitonins in the 2 calendar months prior to enrollment.
[21] Treatment with estrogen as follows:
• oral, transdermal, or injectable estrogens, estrogen analogs, estrogen agonists, and estrogen antagonists in the 3 calendar months prior to enrollment, or for more than 2 months in the 12 calendar months prior to enrollment (with exception of oral estriol).
• intravaginal estrogens in doses more than 1.25 mg conjugated equine estrogen or 25 µg estradiol for more than two doses per week in the 3 calendar months prior to enrollment (with the exception of estriol).
[22] Treatment with progestins or selective estrogen receptor modulators (SERMs) in the 3 calendar months prior to enrollment, or for more than 2 months in the 12 calendar months prior to enrollment.
[23] Treatment with corticosteroids as follows:
Subjects may not be treated with any of the following in the 3 calendar
months prior to enrollment; for more than 30 days in the 12 calendar
months prior to enrollment; or for more than 30 days in any 12-calendar-
month period following enrollment:
• systemic corticosteroids in doses >5 mg prednisone/day orequivalent;
• topical corticosteroids under occlusive dressings in doses >0.5 grams of 0.5% triamcinolone/day or equivalent;
• topical corticosteroids not under occlusive dressings in doses >3 grams of 0.5% betamethasone/day or equivalent;
• orally inhaled or nasally inhaled corticosteroids in doses >400 µg/day beclomethasone or equivalent; or
• more than a single injection of intra-articular corticosteroids in doses >40 mg triamcinolone or equivalent.
Both preenrollment and postenrollment, ophthalmic and otic corticosteroid therapy may be used without limitation.
[24] Treatment with fluorides in the 6 calendar months prior to enrollment or for more than 60 days in the 24 calendar months prior to enrollment. Current use of fluoridated water and topical dental fluoride treatments are permitted.
[25] Treatment with oral bisphosphonates in the 3 calendar months prior to enrollment or for more than 60 days in the 24 calendar months prior to enrollment; treatment with intravenous bisphosphonates in the 24 months prior to enrollment.
[26] Treatment with vitamin D >50,000 IU/week in the 6 calendar months prior to enrollment. Subjects must have a normal 25-hydroxyvitamin D3 laboratory value at enrollment.
[27] Treatment with coumarins and indandione derivatives in the 3 calendar months prior to enrollment; treatment with heparins >10,000 U/day for more than 30 days in the 6 calendar months prior to enrollment.
[28] Treatment with anticonvulsants, except benzodiazepines, in the 6 calendar months prior to enrollment.
[29] Treatment with calcium- or aluminum-containing antacids as follows:
• In the 1 calendar month prior to entry into the calcium and vitamin D run-in phase, not more than five doses per week of calcium- or aluminum-containing antacids for relief of gastrointestinal symptoms.
• From the time the subject is entered into the calcium and vitamin D run-in phase until she completes the study, not more than five doses per week of aluminum-containing antacids will be allowed. Nondietary calcium intake, including the calcium supplements required by the study, shall not exceed 1000 mg elemental calcium
per day.
[30] Treatment with any other drug known to affect bone metabolism (except oral calcium supplementation, vitamin D supplementation less than 50,000 IU/week, or diuretic use that has been stable for 6 months) in the 6 calendar months prior to enrollment.
[32] Known allergy to teriparatide, any diluents or excipients of teriparatide, or to any other form of PTH or PTH analog.
[33] History of prior external beam or implant radiation therapy involving the skeleton
[34] Prior participation in any other clinical trial studying teriparatide, PTH or PTH analog or prior treatment with teriparatide, PTH or PTH analog.
|
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| This is an exploratory study. The primary endpoint in this study is change in whole body skeletal plasma clearance from baseline to 18 months. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | Information not present in EudraCT |
| E.6.2 | Prophylaxis | Information not present in EudraCT |
| E.6.3 | Therapy | Information not present in EudraCT |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Information not present in EudraCT |
| E.6.7 | Pharmacodynamic | Information not present in EudraCT |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | Information not present in EudraCT |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Information not present in EudraCT |
| E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
| E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Information not present in EudraCT |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | Information not present in EudraCT |
| E.8.1.4 | Double blind | Information not present in EudraCT |
| E.8.1.5 | Parallel group | Information not present in EudraCT |
| E.8.1.6 | Cross over | Information not present in EudraCT |
| E.8.1.7 | Other | Information not present in EudraCT |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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 | Information not present in EudraCT |
| E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Information not present in EudraCT |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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 | 3 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
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