E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Low trauma femoral neck fracture |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Musculoskeletal Diseases [C05] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10068399 |
E.1.2 | Term | Trochanteric femoral fracture |
E.1.2 | System Organ Class | 10022117 - Injury, poisoning and procedural complications |
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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 effect of 6 months of treatment with teriparatide 20 μg/day versus placebo on the proportion of men and postmenopausal women ≥50 years of age with successful fracture healing 24 months after internal fixation of a low trauma femoral neck fracture
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E.2.2 | Secondary objectives of the trial |
Comparing the teriparatide group versus the placebo group on:
The proportion of patients with radiographic evidence of healing, no revision surgery, functional evidence of healing, and pain control at 10 weeks, and 6, 12, and 24 months, and over time from 10 weeks to 24 months
The proportion of patients who regain their prefracture ambulatory status at each postsurgical visit and over time from the first postsurgical visit to 24 months
The time to revision surgery over 24 months
Patient-reported outcomes as measured by the mean change in Short Form-12 (SF-12), Western Ontario McMaster Osteoarthritis Index (WOMAC), and European Quality of Life Questionnaire (EQ-5D) from the first postsurgical visit to 6 months.
Safety as assessed by clinical laboratory tests and AEs. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Community dwelling men and postmenopausal women aged ≥50 years who were ambulatory before sustaining a low-trauma, unilateral femoral neck fracture
Other than femoral neck fracture, be free of incapacitating conditions and have a life expectancy of at least 2 years
Have received or are eligible for treatment with internal fixation
Have given written informed consent |
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E.4 | Principal exclusion criteria |
Increased baseline risk of osteosarcoma
History of unresolved skeletal diseases affecting bone metabolism other than primary osteoporosis and any secondary causes of osteoporosis
Abnormally elevated values of serum calcium at baseline
Abnormally elevated values of serum intact parathyroid hormone (PTH) (1-84) at baseline
Severe vitamin D deficiency at baseline defined as 25-hydroxy-vitamin D levels <9.2 ng/mL
Active liver disease or jaundice
Significantly impaired renal function at baseline
Abnormal thyroid function not corrected by therapy
History of a malignant neoplasm in the 5 years prior to Visit 1, with the exception of superficial basal cell carcinoma or squamous cell carcinoma of the skin that has been definitively treated.
History of bone marrow or solid-organ transplantation
History of symptomatic nephrolithiasis or urolithiasis in 1 year prior to visit
Prior treatment with PTH, teriparatide or other PTH analogs
Local or systemic treatment with bone morphogenic proteins or any growth factor
Previous fracture or bone surgery in the currently fractured hip
Treatment with bone grafting or osteotomies
Soft tissue infection at the operation site
Treatment with augmentation using any type of degradable cement, hydroxyapatite-coated implants or with non-invasive interventations
Polytrauma patients and patients with fracture at more thatn 1 site.
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E.5 End points |
E.5.1 | Primary end point(s) |
The proportion of patients with successful fracture healing at 24 months |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
To compare the teriparatide group versus the placebo group on the proportion of patients with
1.radiographic evidence of healing at 10 weeks, and 6, 12, and 24 months and over time from 10 weeks to 24 months.
2.no revision surgery at each postsurgical visit and over time from the first postsurgical visit to 24 months
3.able to ambulate with a gait speed of ≥0,05 meters/second (m/s) at 24 months, with or without a walking aid, and have no clinically significant decrease in gait speed (>0,1 ms/) from baseline to 24 months
4.able to ambulate without severe fracture-site pain at 24 months and have no clinically significant increase in worst fracture-site pain during ambulation from baseline to 24 months
5.able to ambulate with a gait speed of ≥0,05 m/s at 10 weeks, and 6, 12, and 24 months and over time from 10 weeks to 24 months.
6.without severe fracture-site pain in the 24 hours preceding a visit, on weight bearing, and during ambulation at 10 weeks, and 6, 12, and 24 months and over time from 10 weeks to 24 months.
7.who regain their prefracture ambulatory status at each postsurgical visit and over time from the first postsurgical visit
8.The mean change over time from 10 weeks to 6 months in worst fracture-site pain in the 24 hours preceding a visit, on weight bearing and during ambulation
9.The mean change over time from 10 weeks to 6 months in gait speed
10.The time to revision surgery over 24 months
11.Patient-reported outcomes
12. Safety as assessed by lab tests and AEs |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | Yes |
E.6.11 | Pharmacogenomic | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 52 |
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 | No |
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 |
European Union |
Australia |
Austria |
Brazil |
Canada |
Czech Republic |
Denmark |
Finland |
France |
Greece |
Hong Kong |
Hungary |
India |
Israel |
Italy |
Japan |
Korea, Republic of |
New Zealand |
Norway |
Poland |
Romania |
South Africa |
Sweden |
Switzerland |
Taiwan |
Turkey |
United States |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 23 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 4 |