A Multi-center, Randomized, Double-blind, Placebo-controlled Study of AMG 785 in Skeletally Mature Adults with a Fresh Unilateral Tibial Diaphyseal Fracture Status Post Definitive Fracture Fixation with an Intramedullary Nail.

Recruitment & Eligibility

Status: Withdrawn

Sex: Not specified

Target Recruitment: 5

Inclusion Criteria

-Skeletally mature adults, age <= 18 to >= 85 years at randomization, with radiographically closed growth plates
-Fresh unilateral closed or Gustilo type I or type II open tibia diaphyseal fracture (fracture line must not extend into the ankle or knee joint) as the primary injury
-For closed fractures: Definitive fracture fixation with reamed IM nailing (modern, statically, interlocking nail) performed no later than 14 days after injury
-For Gustilo type I/II open fractures: Definitive fracture fixation with reamed or unreamed IM nailing (modern, statically, interlocking nail) performed no later than 24 hours after injury

Exclusion Criteria

-Major polytrauma or significant axial trauma, with injury severity score >16
-Head-injury, as defined by Glasgow Coma Scale <13 at time of randomization
-Use of bone grafts at the time of definitive fracture fixation
-History of pathological fracture or metabolic or bone disease that may interfere with the interpretation of the results, such as Paget*s disease, rheumatoid arthritis, osteomalacia, osteogenesis imperfecta, osteopetrosis, ankylosing spondylitis, Cushing*s disease, hyperprolactinemia
-History of 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
-History of solid organ or bone marrow transplants
-Use of the following agents affecting bone metabolism:
•Intravenous bisphosphonates at any time
•Denosumab at any time
•Fluoride (for osteoporosis) within the past 24 months
•Oral bisphosphonates, parathyroid hormone or strontium within the past 12 months
•Calcitonin, selective estrogen receptor modulators, systemic oral or transdermal estrogen within the past three months (estrogen containing contraceptive therapy is permitted)
•Systemic glucocorticosteroids (* 5 mg prednisone equivalent per day for more than 10 days) within the past three months
•Tibolone within the past three months
•BMP-2 or BMP-7 at the time of definitive fracture fixation
-Current use of anticoagulants (doses for deep vein thrombosis prophylaxis are permitted
-•Known intolerance to calcium supplements or vitamin D products

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>To investigate the effect of AMG 785 compared to placebo on time to<br /><br>radiographic healing of fresh tibial diaphyseal fractures.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>To evaluate the effect of AMG 785 compared to placebo on<br /><br>(1) Physical functioning as measured by Short Form (36) Health Survey Physical<br /><br>Functioning subscale (SF-36 PF)<br /><br>(2) Incidence of unplanned revision surgery<br /><br>(3) Time to clinical healing as determined by the ability to bear weight on the<br /><br>fractured limb and the absence of pain at the fracture site</p><br>