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A Multi-center, Randomized, Double-blind, Placebo-controlled Study to Determine theEfficacy, Safety, and Tolerability of AMG 785 in Adults with Fresh Unilateral Intertrochanteric Fracture of the Proximal Femur, Status Post Fixation with a Sliding Hip Screw or Intramedullary Nail

Conditions
Acceleration of fracture healing
MedDRA version: 12.1Level: LLTClassification code 10016454Term: Femur fracture
Registration Number
EUCTR2009-015939-33-SE
Lead Sponsor
Amgen Inc
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
330
Inclusion Criteria

Adult women or men, age = 55 to = 90 years at randomization

Fresh unilateral low energy intertrochanteric fracture of the proximal femur as the primary injury, confirmed by X-ray

Fractures eligible for this study must have one of the following characteristics
• At least three fragments, each with displacement = 1 cm
• Extension into the subtrochanteric region

Internal fixation of the fracture with a sliding hip screw or IM nail (devices
approved by local regulatory agency), performed no later than 5 days after injury

Pre- and postoperative care performed as defined in Appendix J of the protocol

Subject or subject’s legally acceptable representative has provided informed
consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
;
Adult women or men, age = 55 to = 90 years at randomization

Fresh unilateral low energy intertrochanteric fracture of the proximal femur as the primary injury, confirmed by X-ray

Fractures eligible for this study must have one of the following characteristics
• At least three fragments, each with displacement = 1 cm
• Extension into the subtrochanteric region

Internal fixation of the fracture with a sliding hip screw or IM nail (devices
approved by local regulatory agency), performed no later than 5 days after injury

Pre- and postoperative care performed as defined in Appendix J of the protocol

Subject or subject’s legally acceptable representative has provided informed
consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Conditions that may affect the ability to perform functional or clinical
assessments required by the protocol, such as:

• Severe symptomatic osteoarthritis of the lower extremity
• Inability to independently rise from armchair or walk 200 meters before hip
fracture (use of unilateral assistive device or rolling walker is acceptable)
• Cognitive deficit, as defined by Mini-Mental Status Examination score < 22 at
time of randomization
• Symptomatic neurological conditions such as Parkinson’s disease or persistent
gross motor or sensory deficits such as hemiparesis or hemiplegia
• Presence of concomitant injuries such as rib fractures, wrist fractures, or acute
symptomatic vertebral fractures which severely impair the ability to rise from a
chair
• Associated extremity injuries including ipsilateral or contralateral fractures of the
foot, tibia or fibula, wrist, humerus, femoral shaft, femoral head or hip dislocation,
that may delay weight-bearing beyond one week after surgery

Use of bone grafts or bone substitutes at the time of fracture fixation

Head-injury, as defined by Glasgow Coma Scale <13 prior to randomization

Major polytrauma or significant axial trauma, with Injury Severity Score > 16

Pathological fracture or history of metabolic or bone disease (except
osteoporosis) that may interfere with the interpretation of the results, such as Paget’s disease, rheumatoid
arthritis, osteomalacia, osteopetrosis, ankylosing spondylitis, Cushing’s disease,
hyperprolactinemia

History of symptomatic spinal stenosis

History of facial nerve paralysis

Malignancy (except fully resected cutaneous basal cell or squamous cell
carcinoma, cervical carcinoma in situ) within the last 5 years

Severe asthma or chronic obstructive pulmonary disease or recent exacerbation

Myocardial infarction or unstable angina pectoris within the last 12 months

Current alcohol dependence

History of solid organ or bone marrow transplants

Evidence of the following per subject report, chart review or local laboratory
result (currently or within the past 5 years)

• Elevated transaminases (a) Serum aspartate aminotransferase = 2.0 x
upper limits of normal; (b) Serum alanine aminotransferase = 2.0 x upper
limits of normal
• Significantly impaired renal function as determined by a derived creatinine
clearance of = 30 mL/min using the Modification of Diet in Renal Disease
equation (Levey et al, 1999). The estimated glomerular filtration rate is
calculated as follows: estimated glomerular filtration rate (mL/min/1.73m2)
= 186 x [Serum creatinine (mg/dL)]-1.154 x [Age]-0.203 x [0.742 if subject is
female] x [1.210 if subject is black].
• Current hypocalcemia or hypercalcemia (= 1.1 x upper limit of the normal
range set by the local laboratory, after adequate volume resuscitation, is
acceptable for high calcium value)

Known to have tested positive for human immunodeficiency virus, hepatitis C
virus, or hepatitis B surface antigen

Use of the following agents affecting bone metabolism
• Denosumab within the past 6 months
• Fluoride (for osteoporosis) or IV bisphosphonates within the past 12 months
• Parathyroid hormone or strontium within the past 12 months
• Calcitonin within the past three months
• Systemic glucocorticosteroids (= 5 mg prednisone equivalent per day for more
than 10 days) within the past three months

Bone Morphogenetic Protein (BMP)-2 or BMP-7 at the time of definitive fracture fixation

Subjects to be enrolled in DXA sub-study may not have had previou;
Conditions that may affect the ability to perform functional or clinical
assessments required by the protocol, such as:

• Severe symptomatic osteoarthritis of the lower extremity
• Inability to independently rise from armchair or walk 200 meters before hip
fracture (use of unilateral assistive device or rolling walker is acceptable)
• Cognitive deficit, as defined by Mini-Mental Status Examination score < 22 at
time of randomization
• Symptomatic neurological conditions such as Parkinson’s disease or persistent
gross motor or sensory deficits such as hemiparesis or hemiplegia
• Presence of concomitant injuries such as rib fractures, wrist fractures, or acute
symptomatic vertebral fractures which severely impair the ability to rise from a
chair
• Associated extremity injuries including ipsilateral or contralateral fractures of the
foot, tibia or fibula, wrist, humerus, femoral shaft, femoral head or hip dislocation,
that may delay weight-bearing beyond one week after surgery

Use of bone grafts or bone substitutes at the time of fracture fixation

Head-injury, as defined by Glasgow Coma Scale <13 prior to randomization

Major polytrauma or significant axial trauma, with Injury Severity Score > 16

Pathological fracture or history of metabolic or bone disease (except
osteoporosis) that may interfere with the interpretation of the results, such as Paget’s disease, rheumatoid
arthritis, osteomalacia, osteopetrosis, ankylosing spondylitis, Cushing’s disease,
hyperprolactinemia

History of symptomatic spinal stenosis

History of facial nerve paralysis

Malignancy (except fully resected cutaneous basal cell or squamous cell
carcinoma, cervical carcinoma in situ) within the last 5 years

Severe asthma or chronic obstructive pulmonary disease or recent exacerbation

Myocardial infarction or unstable angina pectoris within the last 12 months

Current alcohol dependence

History of solid organ or bone marrow transplants

Evidence of the following per subject report, chart review or local laboratory
result (currently or within the past 5 years)

• Elevated transaminases (a) Serum aspartate aminotransferase = 2.0 x
upper limits of normal; (b) Serum alanine aminotransferase = 2.0 x upper
limits of normal
• Significantly impaired renal function as determined by a derived creatinine
clearance of = 30 mL/min using the Modification of Diet in Renal Disease
equation (Levey et al, 1999). The estimated glomerular filtration rate is
calculated as follows: estimated glomerular filtration rate (mL/min/1.73m2)
= 186 x [Serum creatinine (mg/dL)]-1.154 x [Age]-0.203 x [0.742 if subject is
female] x [1.210 if subject is black].
• Current hypocalcemia or hypercalcemia (= 1.1 x upper limit of the normal
range set by the local laboratory, after adequate volume resuscitation, is
acceptable for high calcium value)

Known to have tested positive for human immunodeficiency virus, hepatitis C
virus, or hepatitis B surface antigen

Use of the following agents affecting bone metabolism
• Denosumab within the past 6 months
• Fluoride (for osteoporosis) or IV bisphosphonates within the past 12 months
• Parathyroid hormone or strontium within the past 12 months
• Calcitonin within the past three months
• Systemic glucocorticosteroids (= 5 mg prednisone equivalent per day for more
than 10 days) within the past three months

Bone Morphogenetic Protein (BMP)-2 or BMP-7 at the time of definitive fracture fixation

Subjects to be enrolled in DXA sub-study may not have had previou

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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