ACTiF- Assessment of Closed Tibial Fractures

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to find out the good and bad effects of an investigational drug called CP-533,536 in patients with closed fracture of the tibial shaft undergoing internal fixation using reamed inter-locked IM nailing procedure

Official Title
-----------------
A Randomized, Placebo-Controlled Study To Evaluate The Efficacy, Safety And Tolerability Of CP-533,536 In Subjects With Closed Fracture Of The Tibial Shaft

Conditions
-----------------
Tibial Fractures

Intervention / Treatment
-----------------
* Drug: CP-533, 536
* Drug: Placebo
* Procedure: Standard of Care
* Drug: CP-533,536
* Drug: CP-533,536
* Drug: CP-533,536


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Males or females 17 years or older with confirmed closure of the tibial epiphyses, with a closed fracture of the tibial diaphysis undergoing treatment with reamed locked IM nailing procedure and the absence of an associated compartment syndrome or vascular injury; Closed tibial fractures Types A, B & C (See OTA fracture classification) can be included. Exclusion Criteria: Previous fractures of the same tibia that may impact nailing procedure or impaired visibility of current fracture or a history of osteomyelitis; Subjects with any other clinically significant injuries, which may significantly impair weight bearing of the affected limb; Subjects with a fracture gap of >1cm after initial surgery and prior to drug administration; Any other planned invasive or non invasive interventions intended to promote bone healing of the tibial fracture under study are not allowed in the first 24 weeks after treatment.

Ages Eligible for Study
-----------------
Minimum Age: 17 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CP-533,536 Dose Level 2<br> | Drug: CP-533, 536<br>* Active study drug<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo vehicle<br>|
| Other: Standard of Care<br> | Procedure: Standard of Care<br>* Standard surgical procedure<br>|
| Experimental: CP-533,536 Dose Level 1<br> | Drug: CP-533,536<br>* Active study drug<br>|
| Experimental: CP-533,536 Dose Level 3<br> | Drug: CP-533,536<br>* Active study drug<br>|
| Experimental: CP-533.536 Dose Level 4<br> | Drug: CP-533,536<br>* Active study drug<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to fracture healing compared with placebo |  | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who require a secondary intervention to promote fracture healing |  | 48 weeks | 
| Impact on the subject's ability to return to normal function, general health status, work productivity, and degree of pain at fracture site compared with placebo and Standard of Care groups |  | 24 weeks | 
| Time to fracture healing compared with Standard of Care |  | 24 weeks | 
| Proportion of patients healed compared with placebo |  | 16 weeks | 
| Time to regular callus formation compared with placebo |  | 24 weeks |