Clinical trial NCT04170296
Conditions: Edematous Fibrosclerotic Panniculopathy (EFP) Cellulite
Sponsor: Endo Pharmaceuticals
Start date: 2019-11-01; Completion date: 2021-01-08
Enrollment: 153 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This is a multicenter, open-label, multiple dose, 2 cohort, Phase 3b study to assess the safety and efficacy of CCH in adult women with mild or moderate edematous fibrosclerotic panniculopathy (EFP).

Cohort 1 will include approximately 80 subjects with mild or moderate EFP in the posterolateral thighs and Cohort 2 will include approximately 70 subjects with mild or moderate EFP in the buttocks.

Detailed description:

Arms: arm 1: EN3835 up to 1.68mg (Collagenase Clostridium Histolyticum) arm 2: EN3835 up to 1.68mg (Collagenase Clostridium Histolyticum)
Interventions: intervention 1: EN3835
Intervention descriptions: intervention 1: Collagenase Clostridium Histolyticum (CCH)

Protocol documents:
Prot_000.pdf: 


                 
   
      
            
        
   
 
     
      
 
 
 
                                       
 
   
                                                    
            
 
 
   
                                
                           
 
      
                    
        
           
                      
                                   
   
 
                         
          
   
        
              
          
                   
    
                
      
                     
 
                
              
  
                                                     
               
        
        
       
      
                    
           
 
          
           
 
  
           
        
                
          
        
         
    
            
                          
                    
                   
    
                                        
                      
  
                           
     
 
                          
     
  
                                           
      
    
           
    
 
      
       
  
                                  
  
  
      
            
 
                         
          
  
      
                                     
                      
                       
               
                    
          
       
                     
 
             
    
            
                   
 
   
        
    
       
                            
              
         
      
                                         
            
  
        
                                   
      
    
 
             
 
   
                                       
    
             
      
                 
           
              
        
 
   
                         
               
                                    
             
                                      
             
   
    
  
             
      
                    
                                             
     
  
                    
       
 
              
  
 
               
                       
            
      
         
        
                        
          
          
            
                                           
  
            
 
 




                 
   
      
            
        
   
 
     
      
 
 
 
                 
 
                       
           
    
 
      
          
        
  
          
              
  
                 
 
                                          
  
                           
                          
    
         
                            
              
             
           
                           
                       
    
                           
              
             
                                     
              
           
   
            
              
          
                    
            
                                             
      
                                 
    
     
                                     
                       
            
                 
                   
         
            
                              
              
         
                                    
                              
                    
            
                       
 
                                      
 
  
           
                    
              
           
  
   
         
 
                                       
        
           
      
                                
        
    
           
                    
              
              
              
 
                    
           
                 
           
      
       
              
          
      
              
     
            
                                                   
               
 
    
            
      
               
    
 
         
                                                              
 
             
    
            
      
               
    
 
    
                                                      
                                      
                             
   
                 
                    
    
                  
                     
               
              
                                
           
   
                     
                     
     
               
    
            
 
               
         
             
        
           
         
    
                  
                     
               
              
                                
          
   
                     
                                 
       


                 
   
      
            
        
   
 
     
      
 
 
 
        
                                                  
 
    
               
              
 
                
         
   
                 
           
                     
      
     
                
        
      
       
                            
               
            
                     
                                     
       
       
                
        
     
         
       
     
                
        
      
       
                            
               
            
                     
                                     
       
       
                      
         
    
                      
             
      
                           
            
   
                                      
             
  
             
                        
   
                  
              
       
                                    
 
          
                              
            
  
 
        
  
  
         
             
      
                          
             
   
                                      
             
  
             
                                
              
                    
       
                    
        
                
                 
               
             
        
           
   
        
 
                    
 
        
  
  


                 
   
      
            
        
   
 
     
      
 
 
 
                                        
 
   
                                                         
             
 
   
   
        
       
                                   
 
      
     
 
                                  
 
   
 
   
 
    
                
    
    
     
                   
          
           
     
                          
             
                      
                                        
                   
     
              
      
              
                                 
 
             
                    
                                     
   
                
                          
                    
               
                           
 
            
      
                        


                 
   
      
            
        
   
 
     
      
 
 
 
                  
          
 
                                       
 
                                       
 
                                       
 
 
                 
   
  
      
   
  
     
      
   
   
 
           
   
  
            
   
  
          
   
  
         
   
  
   
 
                      
   
 
            
   
  
           
   
  
  
                         
   
  
 
           
   
  
            
 
    
   
 
             
                     
   
  
  
           
 
 
   
  
                     
   
  
   
            
   
  
            
   
 
                
   
  
            
        
   
  
                       
        
   
   
  
   
      
     
   
  
        
             
               
   
   
  
          
     
   
   
   
                         
   
  
        
      
     
   
  
            
      
                 
   




                 
   
      
            
        
   
 
     
      
 
 
 
   
                    
   
   
   
       
         
 
        
   
   
         
   
   
 
        
             
 
                   
   
   
   
   
      
                
   
  
   
          
   
  
   
     
   
   
  
   
        
   
   
  
  
   
   
  
  
  
 
   
   
        
    
   
 
  
   
   
  
           
 
                  
   
   
 
                                   
   
  
   
              
   
  
   
             
   
  
 
                        
   
   
            
   
   
            
   
    
   
      
  
   
    
            
 
               
   
   
           
   
  
           
   
  
                                      
            
   
   
             
     
               
               
   
    
   
         
             
   
    
                 
   
    
   
             
   
    
          
   
    
   
          
   
    
                              
   
    
      
   
       
   
    
          
 
 
   


                 
   
      
            
        
   
 
     
        
 
 
 
    
         
       
   
     
  
      
  
   
   
          
 
                
   
   
             
      
     
                          
                      
    
   
    
         
   
    
 
                 
   
    
   
   
   
   
   
    
   
       
      
       
       
      
  
   
     
   
       
      
 
   
     
   
             
      
  
   
     
                          
      
  
   
   
                                 
               
   
   
   
   
          
  
   
   
   
                                      
      
   
 
  
   
   
            
     
       
  
   
   
                  
       
 
 
   
   
              
    
   
  
                      
   
  
          
   
 


                 
   
      
            
        
   
 
     
        
 
 
 
              
     
     
      
   
   
     
        
   
   
     
 
               
   
 
 






                 
   
      
            
        
   
 
     
        
 
 
 
    
            
   
        
             
    
  
    
          
        
    
  
     
    
  
        
       
       
    
  
      
  
       
         
    
  
      
  
       
         
         
         
   
        
   
         
  
 
 
 
 
 
       
 
     
 
   
 
 
  
  
 
 
 
 
  
         
   
    
  
 
 
 
 
 
    
    
  
 
 
 
 
 
   
 
               
   
 
       
  
 
 
  
  
 
 
 
 
   
           
  
 
 
 
  
  
     
  
 
 
 
 
 
     
  
  
  
  
  
  
   
            
  
 
 
 
 
 
                  
 
  
  
 
 
 
 
        
  
  
 
  
  
  
    
  
 
 
 
 
 
  
         
       
      
  
 
 
 
  
 
                 
  
 
 
 
 
 
                
 
  
  
  
  
  
        
         
    
 
  
 
 
  
  
              
 
 
 
  
 
 
 
 
  
             
                
 
 
 
 
 
  
 
         
     
 
   
  
 
 
 
 
 




                 
   
      
            
        
   
 
     
        
 
 
 
     
       
   
             
              
               
            
    
  
                         
  
            
    
      
                                 
 
            
                                                         
          
                            
                      
      
        
    
                  
           
    
                
       
             
      
                 
    
         
                
  
                           
   
            
 
     
   
     
                        
                                
                   
            
                  
           
                 
  
         
                       
              
                                    
      
 
   
  
               
                 
               
             
                 
  
    
                 
 
     
         
    
                                   
                
     
                        
    
       
   
                                           
                
              
                            
        
                               
                                  
   
    
       
                        
 
           
 
   
  
               
                            
                
                
                 
  
    
         
       
       
         
    
                                   
                
     
                    
  
 
            
  
          
                                     
                 
  
                         
  
           
   
 
   
  
               
                           
                              
                 
  
    
                
       
         
     
                                                      
   
         
                 
                  
      
    
        
                        
           


                 
   
      
            
        
   
 
     
        
 
 
 
   
           
                 
             
        
                  
      
  
      
           
 
   
     
           
       
           
 
 
     
            
                
           
               
 
      
                      
  
         
                 
        
    
      
      
      
                                                     
      
                             
        
       
 
                   
                                    
            
                   
                                                                      
           
           
 
        
      
   
     
                  
                                 
                         
      
   
               
      
         
                                                        
            
 
                                    
                 
          
 
                              
  
 
       
                        
            
                                           
            
  
            
 
          
           
     
                         
                    
         
   
             
        
           
                              
                           
   
 
                                 
 
   
       
 
              
          
                          
   
 
           
     
                      
 
                
              
  
                                                     
               
         
        
       
        
                    
          
 
          
           
 
  
           
        
                
          
        
         
    
            
                          
                     
                    
    
                                        
          
             
     
                                       
                      
     
                        
     
 
                               
  
                                          
        
     
            
    
 
       
        
  
                                    
  
  
      
            
 
                         
          
       
  
         
 
      
                                     
                      
                      
          
    
                    
          
       
                     
 
             
    


                 
   
      
            
        
   
 
     
        
 
 
 
            
                   
 
   
        
     
       
                            
  
              
          
      
                                         
            
  
        
                                   
      
    
 
            
 
   
                            
             
 
                  
      
               
           
              
        
 
   
                         
    
           
                   
             
       
                  
     
          
        
           
              
    
                
     
  
         
                 
               
           
                   
       
       
   
       
           
   
   
   
  
     
      
      
        
             
                
  
     
                          
                                   
   
   
 
                              
              
           
       
    
                      
                       
    
                
     
                 
                          
     
     
         
    
       
   
      
         
         
          
        
                           
                      
       
               
    
            
                 
              
   
                                                
        
     
                                     
                   
          
                                        
        
                   
 
         
                
             
             
             
        
                                  
    
                                    
   
    
       
        
   
 
             
      
  
             
                          
                        
       
 
      
 
                          
 
     
           
                    
             
         
 
     
       
                        
                       
    
      
                 
             
         
               
                                                        
        
        
        
          
       
                 
      
      
   
  
                    
     
                  
                      
                                
   
                      
      
                                
            
             
                                         
       
         
      
                   
                                              
 
                          
              
                 
      
 


                 
   
      
            
        
   
 
     
        
 
 
 
    
 
          
                        
                           
         
               
                
     
                   
      
       
                         
       
     
               
          
            
                     
                      
             
     
                               
   
            
          
                        
    
                            
       
  
  
             
       
    
     
  
 
     
 
      
 
             
    
               
      
  
        
     
  
                          
       
                   
      
    
  
   
           
                                             
       
                
                                  
               
                  
             
     
        
                 
                        
  
        
 
                   
                              
   
      
      
                                  
   
                      
      
    
                           
     
                
         
      
    
   
                      
           
            
   
                
                            
      
        
   
                       
                        
                     
       
                                       
 
 
  
                                 
           
  
   
                       
 
 
     
        
       
 
   
           
                  
              
               
    
      
  
   
       
       
 
  
            
    
                          
                    
  
          
 
   
           
                     
                
             
  
   
       
       
 
  
            
    
                          
                               
  
   
                               
                 
            
 
   
                         
      
                                    
    
   
         
   
      
      
                       
        
   
 
   
                           
 
          
                 
       
 
                         
    




                 
   
      
            
        
   
 
     
        
 
 
 
    
   
    
                  
    
 
         
                      
                                   
          
          
             
   
    
 
  
            
      
                                                        
      
                                                     
                 
         
                           
       
          
                
             
        
              
     
                  
   
  
                                              
                
                                                        
    
           
 
     
    
             
    
         
               
                         
              
  
                                 
                
              
  
         
   
   
             
                      
    
        
          
              
      
                              
                    
   
   
 
       
                      
            
          
                        
  
         
   
               
                                   
       
       
           
             
     
         
                   
     
                               
     
                                 
                   
  
                                     
     
                          
                   
           
             
       
                                          
                     
              
                
                               
   
      
                           
                                 
                  
                
                      
           
  


                 
   
      
            
        
   
 
     
        
 
 
 
                                                             
       
  
       
              
              
             
     
        
                        
   
        
        
                
                
 
         
    
        
             
                          
   
                  
              
                      
                      
     
           
                     
   
                                    
              
                                 
   
 
          
       
   
  
               
               
             
           
   
    
         
          
 
        
                                                 
               
   
                   
            
        
      
          
                              
          
 
   
      
          
                       
    
              
 
 
  
 
       
  
                 
          
                 
                    
   
                
                   
    
         
          
                     
      
                
                    
   
            
     
                                            
   
         
      
                                    
   
  
               
                        
     
        
     
                      
                                    
               
            
          
         
          
       
      
  
       
       
     
       
                             
                       
  
     
     
      
        
 
             
      
                                   
     
                    
                 
 
  
              
          
                
       
                
              
    
                      
                                
                 
        
                    
           
    
  
    
        
        
                   
         
         
                 
 
                       


                 
   
      
            
        
   
 
     
        
 
 
 
                             
                                       
   
 
  
             
        
     
      
       
 
      
        
  
         
             
  
   
  
                
                                      
     
 
  
              
    
           
    
        
         
                        
                       
             
                        
   
             
         
        
                                          
                      
                                                  
           
           
 
     
                              
 
            
 
     
                          
                  
                  
   
                                 
                               
        
        
                                          
 
           
            
  
                                   
    
         
   
    
         
           
 
   
  
    
             
  
     
 
       
                       
          
                 
                  
                   
                        
   
                    
                                        
                           
   
          
     
     
 
                                   
    
  
   
                         
                            
   
  
   
          
   
    
         
     
            
    
                                         
   
                               
 
        
  
        
     
      
                         
   
                       
                
   
                        
                 
    
 
          
                
  
                                             
         
       
                  
              
             
           
        
                                 
           
          
                                      


                 
   
      
            
        
   
 
     
        
 
 
 
                
  
                 
                           
       
            
    
 
      
        
                          
    
         
  
                         
              
       
              
                  
     
 
                                  
 
                 
   
                                           
                       
    
                             
         
                       
        
                      
     
    
 
                  
   
        
                           
              
     
                
 
                                 
   
             
  
        
   
 
                      
  
    
   
                              
       
                   
        
          
                    
       
   
                        
         
   
             
  
                          
     
    
     
                
                                       
                   
             
       
             
                                          
   
          
                         
    
                
     
         
                            
                           
        
       
                           
  
   
                
        
                              
   
            
          
  
               
                                       
    
          
             
              
                           
   
                   
                         
      
                         
    
        
     
         
  
   
                         
                   
              
         
  
   
                         
  
     
  
                                     


                 
   
      
            
        
   
 
     
        
 
 
 
    
                                
       
     
                  
           
   
               
        
   
                                     
                          
              
       
                
                                   
                 
                                     
   
 
   
                       
                                      
      
                        
          
                         
 
   
       
                                               
         
     
                                                   
                 
         
                   
            
       
                   
        
                     
            
    
  
                                                       
         
        
               
     
     
          
       
     
      
                    
                           
                      
                   
                         
         
                   
  
           
            
   
     
 
                    
      
   
   
    
        
 
      
       
     
                
      
     
                  
                      
                             
         
        
     
                                       
                  
     
   
      
                        
               
       
                     
                          
              
                                       
   
              
        
                     
     
               
        
  
       
                             
                  
           
                                 
         
             
          
    
       
                
    
       
             
                             
          
 
  
               
            
             
               
   
   
                
             
                     
            
                     
                
                     
                 
               
                                   
    
            
                                           


                 
   
      
            
        
   
 
     
        
 
 
 
        
            
      
     
        
        
   
    
   
         
       
    
        
    
     
                
    
             
         
  
    
   
        
       
         
 
    
    
          
       
           
            
          
      
           
          
           
         
   
    
                       
                
              
     
             
        
     
          
              
          
              
        
   
         
   
        
       
         
            
          
          
      
         
 
            
         
    
 
           
    
            
        
   
    
                     
               
             
        
       
        
     
       
              
     
             
         
      
      
      
          
       
         
           
        
       
        
   
                   
      
                     
   
    
   
    
                      
                                
                                            
   
  
                                 
     
                       
        
   
                    
       
                                       
          
                           
                     
    
  
 
                        
   
      
                           
        
 
    
 
          
      
          
    
                
  
 
    
               
         
     
        
 
                   
                                   
             
           
       
                   
     
  
                 
            
 
     
                                   
         
        
            
                        
          
         
                        
       
   
               
    
 
                                    
                                         
       
          
        
                         
                          
               
                    
                          
 
             
    
     
                 
         
      
  
                 
            
       
      
      
       
   
            
      
          
       
          
          
   
               
            
 
                     
             
    
                   
    
                            
      
         
               
                      
                      
    
           
                    
          
     
                   
 
                                       
        
           
      
    


                 
   
      
            
        
   
 
     
        
 
 
 
       
    
             
               
              
        
 
              
   
             
                                     
      
 
        
              
      
                      
                        
       
         
     
          
                       
  
    
                              
            
                     
   
                                  
            
           
                 
              
                
 
       
   
   
     
                         
   
                      
                 
                
       
                          
                 
            
   
    
    
    
  
       
 
         
           
         
           
      
       
        
      
            
  
     
       
     
                           
                      
  
                                 
     
  
     
                  
           
      
       
          
         
        
             
                                
     
 
  
          
                     
                 
         
                                 
                            
   
   
                       
    
                              
               
  
           
                               
    
 
               
          
  
  
      
                   
  
     
         
      
                
         
     
         
 
         
           
    
     
         
      
     
  
               
      
                               
 
 
       
     
                           
                
       
          
       
                             
                      
     
      
                                                  
                                                                   
         
    
              
        
               
  
    
                  
                     
                       
      
                                 
           
               
        
                     
             
               
        
              
 
                   
             
 
  
        
    
        
                    
              


                 
   
      
            
        
   
 
     
        
 
 
 
     
             
 
        
            
    
                  
 
                      
    
                         
                                           
                       
            
                
           
    
          
     
    
        
                   
             
                   
                
    
     
    
                        
              
       
  
 
     
    
                            
                 
 
 
             
       
                       
              
                
      
              
                  
   
 
                   
       
            
              
             
           
                
            
                               
  
   
         
          
     
            
        
     
                
   
                 
 
    
         
                      
     
 
       
  
             
 
                           
        
              
                     
                                 
       
          
     
     
 
  
                 
   
   
            
             
     
             
         
                
                                    
        
      
 
                            
 
             
       
     
 
          
      
                                           
   
                                      
        
             
         
    
   
              
      
   
                          
     
                               
           
      
                    
        
          
                 
            
               
                                 
   
                  
      
                    
        
     
       
        
             
            


                 
   
      
            
        
   
 
     
        
 
 
 
  
           
                                
               
                          
                       
              
                   
         
                       
           
                      
 
              
     
                 
   
        
      
  
         
                 
                 
           
                 
                    
                  
  
           
                                                     
     
           
   
     
                  
        
       
               
 
       
     
    
      
                     
   
  
   
                     
                  
               
    
                                            
          
    
     
                       
                   
           
         
    
                        
             
          
                      
              
                     
    
 
                  
                                                 
            
      
    
                
 
      
      
                                
        
          
  
   
                      
       
   
         
        
   
         
            
       
          
           
         
                
       
        
               
            
   
                 
       
          
                        
           
            
            
   
 
                                                                  
    
               
      
                                        
            
                           
                              
    
 
              
    
             
                           
     
            
      
     
                              
    
                   
   
                 
                        
  
     
                
         
     


                 
   
      
            
        
   
 
     
        
 
 
 
    
             
      
       
       
                           
         
        
          
                            
                 
                 
                        
  
          
                                
     
    
           
 
 
                                    
                  
 
     
                                  
                        
         
                  
   
                                  
  
   
      
               
                 
 
             
     
            
   
           
          
                
        
   
               
          
     
                                     
           
       
            
                  
   
                 
                 
  
     
                 
       
  
    
   
                                 
                             
              
       
              
                             
 
                 
              
   
  
        
                                   
               
            
     
    
           
                    
            
                     
    
                          
    
             
 
             
       
                                           
           
         
       
                     
       
         
         
        
     
 
         
       
                
    
                           
     
   
                
     
                                
  
  
                             
                  
                    
             
               
      
                            
                    
             
   
 
            
   
        
 
  
                   
      
  
    
  
      
   
    
     
  
         
                                             
           
       
                         
        
     
           
  
      
 
                                         
  
      
  
 
              
         
         
            
       
            
     
          
    
      
   
                    
     
 
   




                 
   
      
            
        
   
 
     
        
 
 
 
      
     
                     
                    
    
                
                     
                   
       
                              
          
    
          
    
          
   
        
                                      
          
 
                            
 
                                  
  
             
                             
 
   
      
           
   
 
                           
     
   
            
   
       
          
    
                
              
                             
  
      
     
                     
                       
                                       
                   
            
                       
              
          
    
          
   
        
                                      
          
 
                           
 
                                    
  
             
                              
 
         
           
   
 
                           
     
   
            
                  
              
   
       
          
    
                
                        
                   
  
      
         
               
                     
    
                       
               
 
                                                   
               
     
           
     
                           
     
    
  
           
 
                                      
               
                         
      
                           
       
           
     
                                      
   
                                 
                                    
        
                  
           
                   
      
                  
         
             
   
      
                                           
       
           
     
       
                              
    
             
                                      
              
 
                                                        
     
       
     
      
      
                                          
    
   
        
                 
                      
  
       
 
   
         
               
   




                 
   
      
            
        
   
 
     
        
 
 
 
             
        
         
                  
             
                            
          
                 
    
    
  
                                    
                      
       
        
  
 
          
        
                            
    
   
     
          
     
      
      
                        
      
         
                  
 
    
                             
                   
           
                      
      
                               
 
 
     
                 
       
          
       
      
 
    
        
               
    
                                       
               
      
        
        
                  
                         
 
                                   
                
              
                 
     
                
                  
              
                       
                 
  
   
          
                                        
         
         
        
             
                            
  
     
       
       
            
                                              
 
        
 
      
  
                                                 
      
         
   
             
 
  
             
         
                               
                   
  
     
 
                                
   
                                 
         
     
    
        
          
      
           
    
 
                                 
                
                                   
                          
               
       
  
 
          
        
                   
           
   
     
               
    
                
                            
                      
       
                                                    
      
    
               
             
          
     
   
 
  
                
                                    
         
   
                                 
                                            
    
               
               
 
                                  
             
       


                 
   
      
            
        
   
 
     
        
 
 
 
                
                     
           
                    
               
  
 
           
         
                           
    
   
     
                                                               
             
  
                                 
      
           
                   
                   
             
  
        
  
                               
            
   
               
 
                              
        
        
  
               
                  
                     
      
                           
          
                     
                  
     
         
            
 
         
   
        
        
                   
        
     
 
  
                    
          
             
                  
    
                
               
             
             
               
               
      
       
 
 
                  
      
                                          
             
  
             
                    
           
           
   
                                     
      
    
                
        
           
       
                      
                                            
                      
              
        
 
  
          
 
   
    
             
    
                 
                 
         
            
   
           
     
                
    
    
                 
    
                
              
      
 
    
   
                
     
        
   
       
 
  
           
              
      
   
    
       
                
             
 
      
                  
             
                      
    
  
 
                  
      
                             
           
      
    
               
       
 
      
                
                  
               
                   
      
                                     
        
                
 
       
      
    
          
                      
  
      
                                          
    
                                   
     
 
            
     
 
             
              
    
                  
    
             
 
    
            
      
               
    
 
                  
                
                        
       
             
   
 


                 
   
      
            
        
   
 
     
        
 
 
 
                              
                     
                    
                 
 
                    
 
 
     
                               
                         
             
      
                          
                
  
                         
                           
            
           
            
   
                       
              
     
      
        
          
   
      
                 
     
  
  
  
      
                                           
         
          
                            
     
                                
   
     
            
 
  
       
                                                          
 
                                                         
    
                                                     
  
              
          
               
         
                     
       
 
            
    
                                    
                      
              
                     
                       
     
             
               
    
                     
               
             
         
                                    
    
                   
   
        
      
     
  
       
                             
             
 
   
                           
                  
                        
                 
            
        
               
        
            
       
                
       
              
                      
        
     
                     
      
            
                                                
         
     
          
                        
             
   
     
               
                  
            
                              
     
                          
          
      
                                            
          
                    
 
                               
           
              
 


                 
   
      
            
        
   
 
     
        
 
 
 
                       
 
       
                 
       
          
   
                                 
                        
       
        
       
   
     
         
 
                  
       
   
       
     
  
            
  
                
   
                                        
        
     
                    
         
 
            
               
       
             
                                                                    
 
       
    
     
    
         
             
    
          
  
            
               
   
        
         
                 
    
 
  
     
         
                         
          
                      
          
                              
                           
                 
             
                                                
        
                                                       
 
          
         
  
        
                                                
  
     
                                                        
 
  
                              
                        
            
 
           
    
                                         
                    
                          
     
                              
 
    
   
           
     
         
              
       
           
   
    
                           
  
       
                
   
   
    
                      
               
          
      
 
                                     
           
                        
  
   
   
   
     
         
 
      
                               
             
           
   
 
      
                   
     
    
                                        
     
          
              
                       
                         
   
                
                                         
  
    
                                       
 
  
  
        
   
   
                                            
     
      
         
                        
            
     
    
                   
         
     
                         
 
                         
     
     
               
                                      
   
                     
             
   
        
        
      
     
                 
                                           
        
          
      
              
                      


                 
   
      
            
        
   
 
     
        
 
 
 
      
           
               
    
              
   
    
              
            
                  
       
             
   
      
        
     
                               
             
       
            
                  
   
     
      
     
          
                
  
    
             
   
 
          
    
  
          
                          
       
     
          
  
           
         
    
    
                      
             
 
 
          
   
 
    
                
         
  
                                  
                         
   
                   
  
      
 
                
  
                   
               
                  
    
               
        
                                        
                  
                                    
         
      
             
  
               
                                   
 
      
                                            
 
           
                                        
    
                         
               
                       
                   
                
           
       
          
 
           
    
                
   
          
 
    
 
           
                     
       
   
      
                       
    
                               
                 
             
    
            
     
  
  
    
              
     
  
  
    
     
     
  
  


                 
   
      
            
        
   
 
     
        
 
 
 
    
        
     
            
      
  
           
      
         
                                
   
 
                     
                           
            
  
    
 
                 
      
                  
               
   
                                   
 
                     
                                               
   
                                              
   
          
   
   
                                              
       
        
            
                           
  
     
           
          
                          
              
        
  
                 
 
    
                
    
          
           
        
                           
 
         
   
 
   
     
                 
   
    
                          
                       
    
                 
                      
   
  
     
             
  
          
       
   
     
  
   
   
                                   
    
                
    
              
  
          
              
               
     
   
  
                             
             
  
             
                                                    
      
  
   
 
                                           
       
    
           
                                         
       
      
          
         
       
       
     
          
    
      
       
                                                                          
 
        
         
    
    
          
  
                  
                
             
               
      
              
                          
       
   
                 
                         
    
            
     
      
              
                         
       
                                  
   
                
  
                    
     
    


                 
   
      
            
        
   
 
     
        
 
 
 
    
 
                      
 
                       
        
     
                           
            
    
      
  
    
                   
   
            
    
  
     
            
     
   
                    
        
  
                   
     
                                     
       
         
  
   
    
      
    
      
                       
            
                        
             
         
    
        
   
         
      
            
   
     
 
           
     
                              
                             
      
          
  
   
           
                  
       
     
          
             
                    
    
         
    
          
              
      
      
          
          
             
                
    
                                 
            
 
  
              
     
                          
    
      
           
                    
         
   
                                                
       
                                  
   
     
            
            
   
                    
                 
      
   
   
             
                       
   
    
         
  
                                      
         
                      
 
    
        
  
                  
       
        
           
 
   
                   
 
               
   
              
              
   
        
  
                   
                                
                                                                   
   
  
                   
              
        
 
                     
 
  
       
    


                 
   
      
            
        
   
 
     
        
 
 
 
    
                                     
            
     
                                       
  
       
      
                            
 
                            
                           
         
      
 
                                                                 
  
   
    
       
   
 
                                   
   
  
                                                            
              
    
        
                    
      
                            
    
                      
       
                        
         
                  
            
        
                          
              
             
          
            
 
       
       
                        
        
       
                 
     
    
  
    
   
         
         
       
               
       
             
       
                        
              
    
           
     
         
             
   
   
      
      
   
     
  
                         
  
 
  
 
                   
     
 
   
 
 
     
               
  
                      
     
  
           
      
                  
  
        
               
     
                  
    
               
          
         
         
       
                
                     
             
                
                           
         
                
   
     
                                                           
  
    
   
        
                 
                      
       
  
                                       
     
                       
           
                           
     
   
     
         
                            
              
       
   
   
        
      
                                     
               
                                                         
                       
                                      
 
   
             
           
     
                          
   
 
       
      
             
   
                     
           
  
 
 
      
                     
                                   
     
     
                 
      
 
                   
              
         
 
                                     
      
        
          
    
 
   


                 
   
      
            
        
   
 
     
        
 
 
 
      
       
       
       
              
    
                 
   
             
 
   
                                   
     
                 
 
 
                
 
           
      
       
          
    
     
   
            
           
      
             
                 
               
             
      
                      
        
                                
                              
              
                  
                
                         
      
  
  
                   
          
        
            
  
  
 
 
      
                
          
 
 
                             
                  
    
              
           
     
                                       
                
     
  
                 
          
         
   
                             
                            
  
      
       
           
    
      
  
                                
                     
                  
       
    
  
      
  
                                                   
         
          
 
            
                                                   
 
  
   
     
         
                 
             
       
      
     
            
  
                       
           
            
   
 
                
   
     
                
   
                  
    
                
   
             
             
           
             
 
         
     
       
             
                        
        
     
   
            
  
    
                     
      
  
     
                                       
            
                             
        
    
             
    
 
                    
                                             
   
                         
 
     
            
      
        
    
        
  
                    
                             
                     
 
              
              
          
  
           
       
                        
 
    
         
 
     
         
       
       
     
          
        
                   
      
                       
                                   
            
   
 
       
             
   
         
       
       
       
         
                 
        
  
           
          
    
                       
         
  
  
       
            
       
       
  


                 
   
      
            
        
   
 
     
        
 
 
 
      
   
           
                                        
           
        
      
           
              
          
      
                                
      
      
      
                
    
   
        
           
                      
     
                         
         
    
      
      
   
         
                         
 
                   
         
          
 
        
           
   
                    
            
     
   
    
      
     
                
           
                
                         
                     
       
    
               
 
       
              
                 
    
 
 
     
                                 
       
    
     
          
          
  
    
        
      
              
  
                       
        
                                       
              
      
  
                                                     
      
            
                                                       
        
                                                     
                             
          
                 
      
     
                                             
  
     
   
          
                                  
  
                     
            
                      
                                           
                                      
        
   
                  
               
            
      
                    
                          
              
   
           
   
     
   
  
 
                                          
                         
                                          
                   
  
 
                  
    
                      
 
                
   
      
                               
 
      
                
                     
                  
      
             
  
         
                      
     
    
                    
   
                  
    
        
        
          
 
                 
       
         
 
                     
    
 
                
   
          
   
    
       
      
 
                   
    
  
 
    
 
     
   
  
 
         
   
    
                                  
                           


                 
   
      
            
        
   
 
     
        
 
 
 
    
              
          
                             
         
                                        
   
                                               
                        
      
               
                   
                          
   
  
  
      
 
                             
                     
        
                        
                         
      
     
  
                              
                    
             
           
                          
                      
 
            
                                         
  
     
        
 
     
       
   
          
           
 
                        
       
 
 
                        
 
                          
    
                     
      
 
                
 
       
           
          
 
      
         
          
                                               
          
     
                               
       
    
         
               
                                             
  
     
                    
             
  
            
                  
                    
            
                 


                 
   
      
            
        
   
 
     
        
 
 
 
     
          
               
  
        
                    
        
           
   
   
         
  
  
  
           
                
 
   
    
   
  
       
      
        
    
      
            
 
     
       
 
         
       
       
       
         
     
   
               
                  
    
                   
    
              
     
     
      
      
                    
      
       
     
   
       
   
       
     
  
       
   
   
 
        
 
               
      
  
               
       
          
   
     
                    
     
               
    
             
                       
      
   
    
                
                          
     
  
            
     
                     
         
          
            
   
   
       
                               
 
                    
     
 
             
 
          
                                      
  
              
                          
              
               
  
         
              
    
                                            
      
   
      
                         
                                
   
                  
    
      
   
        
                
        
                     
       
               
                     
       
   
        
 
       
                 
                
   
         
              
  
                
   
                                 
                   
     
      
          
                     
       
    


                 
   
      
            
        
   
 
     
        
 
 
 
                        
      
         
   
   
        
                    
 
                        
   
    
                                 
                    
  
                
      
                 
      
             
      
    
    
                                          
            
      
      
        
  
    
      
        
  
  
       
  
  
               
        
   
   
               
  
           
             
            
 
         
     
        
  
   
    
                  
       
       
 
      
             
                   
    
 
      
 
 
      
              
        
 
      
                           
            
                     
      
        
 
            
   
       
       
        
                
                   
   
                 
      
              
                       
      
      
                      
             
                           
 
        
            
      
             
      
                                
             
 
    
                                                         
 
                          
                                          
    
                  
 
                            
                            
              
   
 
                                 
 
    
                                                                
   
 
                               
 
    
         
   
        
             
           
     
        
  
    
       
       
       
                  
        
       
 
   
  
                  
   
   
 
  
                            
       
       
           
              
               
        
                                
  
           
        
                                           
        
                             
            
                                
   
                      
      


                 
   
      
            
        
   
 
     
        
 
 
 
      
       
        
      
         
              
      
                    
   
    
          
     
         
    
              
   
         
             
   
                                     
                          
     
               
                
                    
  
       
          
   
        
                              
  
 
                 
   
      
                  
                       
  
                         
  
                     
         
                    
                 
  
                            
          
 
 
     
                  
 
     
                                    
         
     
             
  
         
      
      
    
              
                        
 
 
    
                       
 
               
                   
 
      
        
    
 
        
           
     
     
     
        
     
      
     
                          
               
        
                              
                           
        
 
              
               
            
             
                
        
     
                           
 
           
           
     
        
  
  
                                
  
                      
                  
      
            
        
 
       
           
   
                     
                    
  
       
      
           
         
   
                          
      
                          
               
                   
                  
     
                              
        
 
                         
                        
              
                   
        
                   
             
         
  
  
                                    
            
 
        
              
                
                      
          
      
            
                 
                  
      
        
                    
   
      
            
             
          
        
      
       
        
 
 
                               
       
 


                 
   
      
            
        
   
 
     
        
 
 
 
         
                       
           
                   
   
   
         
                                                
 
           
                        
      
       
              
                 
           
     
   
                                             
  
         
                                         
            
         
 
   
     
 
                           
      
  
                                                        
           
   
           
                     
                   
            
          
         
                          
                     
  
                                         
                          
                  
                  
  
         
         
       
                                  
           
                 
                 
                  
        
              
     
 
                                               
     
                 
                 
 
              
     
   
                          
     
                
     
  
  
     
                        
                   
 
   
  
     
              
                     
      
     
      
      
                          
                                   
  
           
     
        
                             
 
     
    
 
                       
                                      
 
    
     
  
 
   
   
    
 
    
                 
      
 
                     
   
            
     
    
      
     
                          
  
     
  
  
     
                   
          
  
     
  
  


                 
   
      
            
        
   
 
     
        
 
 
 
     
               
    
     
     
     
    
   
            
    
                
    
  
    
         
  
     
   
 
   
   
     
       
   
 
   
   
     
       
     
          
  
       
       
   
              
    
                
    
       
       
           
    
      
     
 
    
  
       
     
  
     
                          
   
     
           
     
   
        
     
    
          
 
     
        
     
            
  
    
    
    
                
     
    
      
         
     
             
  
             
   
  
   
               
    
                 
       
  
   
    
   
            
      
   
    
   
          
  
               
   
   
              
   
            
      
   
 
        
       
   
                        
    
 
              
    
                 
      
                                   
     
                         
    
     
         
   
         


                 
   
      
            
        
   
 
     
        
 
 
 
    
                      
                                    
                
       
  
       
  
   
                       
          
 
 
  
                 
       
         
    
 
 
 
        
            
 


                 
   
      
            
        
   
 
     
        
 
 
 
    
           
      
           
    
    
             
        
             
             
                                         
                          
  
        
            
             
                    
 
      
                                      
            
           
     
      
   
          
          
             
           
                             
               
          
                                   
  
                           
                
                    
          
      
           
  
   
                          
     
      
       
              
  
        
                                
    
 
   
 
   
      
 
                                     
      
                       
                          
     
      
    
           
       
                  
    
   
                  
                             
                           
                          
          
 
          
                             
               
          
                   
                     
        
                      
              
        
             
           
            
 
              
     
                                  
                                  
                    
               
                           
            
                        
                     
           
                            
                        
             
 
                
       
                                
       
                   
     
      
         
     
   
                                  
      
      
  
     
 
                             
  
         
                 
                    
                        
                  
                             
   
              
                                           


                 
   
      
            
        
   
 
     
        
 
 
 
           
          
                                             
                 
    
                        
      
          
      
                                                   
                          
     
   
          
             
      
           
                  
 
              
       
                       
 
             
     
             

SAP_001.pdf: