E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Postmenopausal women with severe osteoporosis |
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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 |
The primary objective is to demonstrate that combination therapy with once yearly i.v. zoledronic acid and daily subcutaneous injections of teriparatide is non-inferior to teriparatide treatment alone with respect to percentage increase in lumbar spine BMD at 52 weeks. If the non-inferiority is established, the superiority of the combination therapy is to be evaluated. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are:
• To evaluate the effect of combination therapy with zoledronic acid and teriparatide compared to teriparatide alone on percent change in total hip BMD at 52 weeks. • To evaluate the effect of combination therapy with zoledronic acid and teriparatide compared to teriparatide alone on percent change of lumbar spine and total hip BMD at 13 and 26 weeks. • To evaluate the effect of combination therapy with zoledronic acid and teriparatide compared to zoledronic acid alone on percent change in lumbar spine and total hip BMD at 13, 26 and 52 weeks. • To evaluate the effect of combination therapy with zoledronic acid and teriparatide compared to teriparatide alone and zoledronic acid alone on serum biochemical markers (P1NP and β-CTx) at 4, 8, 26, 39 and 52 weeks.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Female, between 45 and 89 years of age. Postmenopausal status is according to the following guidelines: (a) cessation of menses for 18 months in women < 50 years of age (b) cessation of menses for 12 months in women age 50 or over (c) documented bilateral oophorectomy at least 1 year prior (d) T score of -2.5 or less for BMD at femoral neck, total hip or lumbar spine. (e) T score of -2.0 or less at femoral neck, total hip or lumbar spine with at least one documented osteoporotic vertebral fracture or a previously documented history of an osteoporotic clinical non-vertebral fracture not due to excessive trauma
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E.4 | Principal exclusion criteria |
• Any prior use of strontium. • Calculated creatinine clearance < 30 mL/min. • Urine dipstick greater than/similar to 2+ protein at Visit 2 without evidence of contamination or bacteriuria. • Prior treatment with oral or i.v. bisphosphonates longer than 3 months consecutively. If bisphosphonate exposure is less than or equal than 3 months, a washout period of 1 year prior to randomiztion is required. • Serum calcium greater than or similar to 2.75 mmol/L or ≤ 2.0 mmol/L. • 25(OH) vitamin D levels less than 20 ng/ml prior to randomization. • AST or ALT greater than 3 times the upper limit of normal. • Serum alkaline phosphatase (SAP) greater than 1.5 times the upper limit of normal. • Non-osteoporotic forms of metabolic bone disease, such as and not limited to, Paget’s disease of bone, osteomalacia, osteogenesis imperfecta or multiple myeloma. • Less than 3 evaluable lumbar (L1-L4) vertebrae. • Treatment with SERMs (i.e. raloxifene), calcitonin or HRT within 3 months of randomization. • Allergy or previous exposure to teriparatide. • Previous exposure to exogenous PTH or PTH analogs.
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E.5 End points |
E.5.1 | Primary end point(s) |
To demonstrate that combination therapy with once yearly i.v. zoledronic acid (5 mg) and daily subcutaneous injections of teriparatide (20 micro gram) is non-inferior to teriparatide treatment alone with respect to percentage increase in lumbar spine BMD at 52 weeks. If the non-inferiority is established, the superiority of the combination therapy (ZOL+PTH) over teriparatide treatment alone is to be evaluated. |
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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 | No |
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) | Information not present in EudraCT |
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 | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
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 | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 18 |
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 | 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
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An unexpected widespread saftey issue may be a reason. |
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |