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 | 100000004863 |
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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 |
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. |
|
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 (displaced or non-displaced)
-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 (sliding hip screw or multiple cancellous screws) for the femoral neck fracture (the surgical procedure itself is not a part of this protocol)
-Have given written informed consent (patient or proxy) after being informed of the risks, medications and study procedures |
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E.4 | Principal exclusion criteria |
-Increased baseline risk of osteosarcoma; this includes patients with
Paget's diseaseof the bone, previous primary skeletal malignancy, or
skeletal exposure to therapeutic irradiation, including external beam
therapy or brachytherapy. As elevation of serum alkaline phosphatase
may indicate the presence of Paget's disease, an unexplained elevation
of this enzyme is also exclusionary.
-History of unresolved skeletal diseases affecting bone metabolism other
than primary osteoporosis including renal dystrophy, osteomalacia,
including glucocorticoid-induced osteoporosis, hyperparathyroidism
(uncorrected), and intestinal malabsorption
-Abnormally elevated values of serum calcium at baseline defined as ≥
10,6 mg/dL, except for clinically insignificant values as determined by
the investigator in conjunction with the Lilly clinical research physician
-Abnormally elevated values of serum intact parathyroid hormone (PTH)
(1-84) at baseline defined as >72 pg/mL
-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 based on serum
creatinine and/or measured or calculated creatininethat, in the opinion
of investigator, indicates significant renal impairment
-Abnormal thyroid function not corrected by therapy
-History of 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. Patients with carcinoma in
situ of the uterine cervix treated definitively more than 1 year prior to
screening may enter the study.
-History of bone marrow or solid-organ transplantation
-History of symptomatic nephrolithiasis or urolithiasis in the 1 year prior
to Visit 1
-Previous treatment with the following bone active drugs is allowed but
must be discontinued at Visit 1: oral bisphosphonates, selective estrogen
receptor modulators, calcitonin, estrogen (oral, transdermal or
injectable), progestin, estrogen analog, estrogen agonist, estrogen
antagonist or tibolone, and active Vit D analogues. Androgen or other
anabolic steroid use must be discontinued, except for use of physiologic
replacement testosterone.
-Previous treatment with the following bone active drugs is
exclusionary, if the stated treatment durations have been met: strontium
ranelate for any duration, intravenous bisphosphonates in the 12 months
preceding Visit 1, and/or denosumab in the 6 months preceding Visit 1
-Prior treatment with PTH, teriparatide, or other PTH analogs, or prior
participation in any other clinical trial studying PTH, teriparatide or other
PTH analogs
-Local or systemic treatment with bone morphogenic proteins or any
other growth factor
-Previous fracture(s) or bone surgery in the currently fractured hip
-Soft-tissue infection at the operation site
-Treatment with bone grafting or osteotomies
-Treatment with augmentation using any type of degradable cement,
hydroxyapatite-coated implants, or with noninvasive interventions
- Associated major injuries of a lower extremity including fractures of
the foot, ankle, tibia, fibula, knee, femur, femoral head, or pelvis:
dislocations of the ankle, knee, or hips. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: The overall success of femoral neck fracture healing will be
determined in each patient based on revision surgery.
Health Outcomes/Quality of Life: Measured using the SF-12, WOMAC and
EQ-5D. A questionnaire will also be used to measure health-care
resource use.
Safety: Evaluated by analysis of clinical laboratory tests and adverse
events
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|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
To compare the teriparatide group versus the placebo group on the
proportion of patients with
- radiographic evidence of healing at 10 weeks, and 6, 12, and 24
months and over time from 10 weeks to 24 months.
- no revision surgery at each postsurgical visit and over time from the
first postsurgical visit to 24 months
- 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 (≥10 weeks)
to 24 months
- able to ambulate without severe fracture-site pain (<7 on pain Numeric
Rating Scale [NRS]) at 24 months and have no clinically significant
increase in worst fracture-site pain during ambulation (increase of >2 on
pain NRS) from baseline (≥10 weeks) to 24 months
- 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.
- without severe fracture-site pain (NRS score of <7) 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.
- who regain their prefracture ambulatory status at each postsurgical
visit and over time from the first postsurgical visit
- The mean change over time from 10 weeks to 6 months in worst
fracture-site pain in the 24 hours preceding a visit, on weigh bearing and
during ambulation
- The mean change over time from 10 weeks to 6 months in gait speed
- The time to revision surgery over 24 months
- Patient-reported outcomes as measured by the mean change over time
from the first postsurgical visit to 6 months on the following:
• Short Form 12 (SF-12) physical and mental component summary
scores
• Western Ontario McMaster Osteoarthritis Index (WOMAC)
• European Quality of Life Questionnaire (EQ-5D)
- Safety as assessed by clinical laboratory tests and adverse events
(AEs)
Endpoints are of equal importance |
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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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 27 |
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 | 4 |
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 | 4 |
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 |