E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of postmenopausal osteoporosis |
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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 |
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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 describe the safety and tolerability of up to 5 years denosumab administration as measured by adverse event monitoring, immunogenicity, and safety laboratory parameters in subjects who previously received denosumab. |
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E.2.2 | Secondary objectives of the trial |
To describe the -effect of AMG162 admin on changes in lumbar spine, total hip and distal radius Bone Mineral Density (BMD) in subjects who previously received AMG162 and in subjects who previously received placebo. -incidence of vertebral and non vertebral fractures following AMG162 administered in subjects who previously received AMG162 and in subjects who previously received placebo. -effect of AMG162 admin on markers of bone turnover in subjects who previously received AMG162 and in subjects who previously received placebo. -change in serum calcium values between the Baseline and Day 10 visit in subjects who previously received AMG162 and in subjects who previously received placebo. -effect of up to 5 yrs AMG162 admin on bone histology in subjects who previously received AMG162. -safety and tolerability of up to 2 yrs AMG162 admin as measured by adverse event monitoring, immunogenicity, and safety laboratory parameters in subjects who previously received placebo.
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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 markers sub-study (29 May 2007) – Serum for biochemical markers (Type 1 CTX, iPTH, RANKL, OPG, BALP, P1NP) will be collected in a subset of subjects who participated in the 20030216 bone marker substudy at Day 10, month 6, month 12 and month 24 visits to assess the effect of denosumab treatment on bone turnover and other bone parameters.
DXA sub-study (29 May 2007) – Subjects who participated in the 20030216 DXA sub-study will be requested to undergo additional bone densitometry assessments of the distal radius at the month 12 and month 24 visits
Transiliac bone biopsy sub-study (29 May 2007) – A target of approximately 50 subjects who received denosumab therapy for 5 years will be approached to undergo a transiliac bone biopsy within 56 days before the final study visit, to assess the effect of denosumab on bone histology and histomorphometry.
Pharmacokinetics (PK) and Pharmacodynamics (PD) Sub-Study (25 October 2007) - Serum for denosumab levels (PK) and CTX-1 (PD) will be collected at Day 10, months 3, 4 and 6 in approximately 225 subjects who previously participated in the 20030216 PK sub-study. |
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E.3 | Principal inclusion criteria |
Subjects must sign the informed consent before any study specific procedures are performed and agree to receive denosumab 60mg SC injection every 6 months
Subjects must not have discontinued investigational product during the 20030216 study and must have attended the 20030216 study month 36 visit |
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E.4 | Principal exclusion criteria |
- Permanently non-ambulatory subjects (use of an assistive device e.g. cane, walker etc is permitted) - Missed two or more investigational product doses during the 20030216 study - Any disorder that, in the opinion of the investigator, may compromise the ability of the subject to give written informed consent and/or comply with study procedures - Developed sensitivity to mammalian cell derived drug products during the 20030216 study - Unable to tolerate calcium supplementation during the last 6 months of participation in the 20030216 study (between the month 30 and month 36 20030216 study visits) - Receiving any investigational product other than denosumab - Current use of the following osteoporosis agents: bisphosphonates, calcitonin, fluoride, parathyroid hormone, selective estrogen receptor modulators, systemic oral or transdermal estrogen (except vaginal preparations and estrogen creams which are acceptable), strontium or tibolone - For bone biopsy sub-study subjects only: known or suspected sensitivity or contraindication to tetracycline derivatives
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is safety monitoring, including adverse event incidence, serious adverse event incidence, changes in safety laboratory analytes (serum chemistry, hematology) and subject incidence of anti-denosumab antibody formation in subjects previously treated with denosumab who receive up to 5 years of denosumab administration. |
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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) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
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 | No |
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) | No |
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.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 148 |
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 | Yes |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 10 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 0 |