Conditions: Presbyopia Refractive Errors Eye Diseases
Keywords: Pharmaceutical Solutions Miotics Ophthalmic Solutions Near Vision Eye Drops INSIGHT 2
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 59
Healthy volunteers: yes

Brief summary:
To evaluate the safety and effectiveness of Aceclidine/Brimonidine (LNZ101) compared with Aceclidine (LNZ100) and vehicle in the treatment of Presbyopia.

Detailed description:

Arms:
arm 1: LNZ 101: Aceclidine/Brimonidine combination ophthalmic solution arm 2: LNZ 100: Aceclidine ophthalmic solution arm 3: Proprietary vehicle ophthalmic solution

Interventions: intervention 1: Aceclidine+Brimonidine combination ophthalmic solution intervention 2: Aceclidine ophthalmic solution intervention 3: Vehicle proprietary ophthalmic solution
Intervention descriptions: intervention 1: LNZ101-combination ophthalmic solution intervention 2: LNZ100- aceclidine ophthalmic solution intervention 3: Proprietary Vehicle ophthalmic solution

Protocol document:
Prot_000.pdf: 








 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
  
 
 




 
 
 
 
 
 
 
 
  
 
 


 
 
 
 
 
 
 
 
  
 
 




 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
 
 
 
 
 
  
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 






 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
  
 
 
 
  
 
 
 
  
 
 
 
 
  
 
 
 
 
  
 
 
 
  
 
 
 
 
 
  
 
 
 
 
  
 
 
 
  
 
 
 
 
 
  
 
 
 
  
 
 
 
  
 
 
 
 
  
 
 
 
 
  
 
 
 
  
 
 
 
  
 
 
 
  
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
  
 
  
 
 
 
  
 
 
 
  
 
 
 
  
 
 
 
 
 
  
 
 
 
  
 
  
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
  
 
 
 
  
 
 
 
  
 
 
 
  
 
 
 
  
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
  
 
 
 
  
 
 
 
  
 
 
  
 
  
 
 
  
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
  
 
  
 
 
 
 
  
 
  
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
  
 
 
 
 
  
 
 
 
  
 
 
 
 
 
  
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
  
 
 
 
  
 
 
   
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
  
  
  
 
 
 
 
  
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
  
 
  
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 








 
 
 
 
 
 
 
 
 
 
 
 














 
 
  
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 






 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 














 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
   
 
 
 
 
 
 
   
 
 
  
 
 
 
 
 
  
 
 
 
 
 
  
  
 
 
 
 
   
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
  
 
 
 
 
  
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 




 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 




 
 
 
 
 
 




 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 


 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
 
 
 
  
 
 
 
 
  
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 


 

SAP_001.pdf: 
 
STATISTICAL ANALYSIS PLAN  
A Multicenter, Double-Masked Evaluation of the 
Safety and 
Effectiveness of 
 (LNZ101) and 
 (LNZ100) in the Treatment of Presbyopia 
 
 
Sponsor: 
 
LENZ Therapeutics, Inc. 
  
 
 
 
 
 
Protocol Number: 
22-100-0003 
 
 
Author:  
 
 
 
 
 
 
Statistics & Data Corporation 
 
Date:    
 
12JAN2023 
Version:  
 
1.0 
 


Page 2 of 37
A Multicenter, Double-Masked Evaluation of the Safety and Effectiveness
of 
 
LNZ101) and 
LNZ100) in the Treatment of Presbyopia
Protocol Number:
22-100-0003
SAP Version: 
1.0
SAP Date: 
12JAN2023
Statistical Analysis Plan Approval


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Table of Contents
List of Abbreviations.............................................................................................................................5
1.
Introduction...............................................................................................................................6
2.
Study Objectives ......................................................................................................................6
2.1
Study Variables ........................................................................................................................6
2.2
Primary Efficacy Variable .........................................................................................................6
2.5
Safety Variables .......................................................................................................................7
2.7
Statistical Hypotheses..............................................................................................................8
3.
Study Design and Procedures .................................................................................................8
3.1
General Study Design ..............................................................................................................8
3.2
Schedule of Visits and Assessments .......................................................................................8
4.
Study Treatments...................................................................................................................10
4.1
Method of Assigning Subjects to Treatments ........................................................................10
4.2
Masking and Unmasking........................................................................................................10
5.
Sample Size and Power Considerations................................................................................11
6.
Data Preparation ....................................................................................................................11
6.1
Input Data...............................................................................................................................11
6.2
Output Data............................................................................................................................12
7.
Analysis Populations ..............................................................................................................12
7.1
Modified Intent-to-Treat..........................................................................................................12
7.2
Intent-to-Treat.........................................................................................................................12
7.3
Per Protocol............................................................................................................................13
7.4
Safety .....................................................................................................................................13
8.
General Statistical Considerations.........................................................................................13
8.1
Unit of Analysis.......................................................................................................................13
8.2
Missing or Inconclusive Data Handling ..................................................................................13
8.3
Definition of Baseline .............................................................................................................14
8.5
Data Analysis Conventions ....................................................................................................15
8.6
Adjustments for Multiplicity.....................................................................................................15
9.
Disposition of Subjects...........................................................................................................15
10.
Demographic and Pretreatment Variables.............................................................................16
10.1 Demographic Variables..........................................................................................................16
10.2 Pretreatment Variables ..........................................................................................................16






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1. Introduction 
The purpose of this statistical analysis plan (SAP) is to describe the planned analyses and reporting for 
protocol 22-100-0003, Amendment 2 dated 19JUL2022. 
This SAP is being written with due consideration of the recommendations outlined in the most recent 
International Conference on Harmonisation (ICH) E9 Guideline entitled Guidance for Industry: Statistical 
Principles for Clinical Trials and the most recent ICH E3 Guideline, entitled Guidance for Industry: Structure 
and Content of Clinical Study Reports. 
This SAP describes the data that will be analyzed and the subject characteristics, efficacy, and safety 
assessments that will be evaluated. This SAP provides details of the specific statistical methods that will 
be used. The statistical analysis methods presented in this document will supersede the statistical analysis 
methods described in the clinical protocol. If additional analyses are required to supplement the planned 
analyses described in this SAP, they may be completed and will be identified in the clinical study report. 
2. Study Objectives 
To evaluate the safety and effectiveness of 
 (LNZ101) compared with 
 (LNZ100) and vehicle in the treatment of presbyopia. 
2.1 
Study Variables 
2.2 
Primary Efficacy Variable 
The primary efficacy variable is the following: 
 
Percentage of subjects who achieve a 3-line (15-letter) or greater improvement from pre-treatment 
in the measurement of 
 monocular best-corrected distance visual acuity 
(BCDVA) at 40 cm and no loss in BCDVA  5 letters (Early Treatment Diabetic Retinopathy Study 
[ETDRS] chart at 4 m) 
 


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2.5 
Safety Variables 
The safety variables include the following: 
 
Loss of BCDVA 
 
Low-luminance BCDVA 
 
Slit-lamp biomicroscopy and fundoscopy 
 
Conjunctival redness
 
 
Intraocular pressure (IOP) 
 
 
Adverse Events (AEs) (reported, elicited, and observed) 


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2.7 
Statistical Hypotheses 
The clinical hypothesis is that LNZ101 is non-inferior to LNZ100 and superior to vehicle in improving near 
vision in subjects with presbyopia. An additional hypothesis for this study is LNZ101 also improves efficacy 
duration in comparison to LNZ100. 
3. Study Design and Procedures 
3.1 
General Study Design 
This is a randomized, double-masked, multi-center, crossover study evaluating the safety and efficacy of 
an 
 (LNZ101) compared with 
 (LNZ100) and vehicle in 
approximately 60 subjects with presbyopia. At the first study visit (Visit 1)
 
 
 
 
.
subjects will receive one of the following treatments based on 
the randomized sequence they are assigned at Visit 2: 
 
 
(LNZ101) administered bilaterally 
 
(LNZ100) administered bilaterally 
 
Vehicle (non-preserved) ophthalmic solution administered bilaterally 
All subjects will receive each treatment once (crossover study design). 
Wherever applicable, study visits will be referred to tables and listings as the expected study day 
corresponding to the visit to enable reviewers to understand the assessment timing without referring to the 
protocol visit schedule. . 


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Table 1 shows the scheduled study visits, their planned study day, and the acceptable visit window for each 
study visit: 
3.2 
Schedule of Visits and Assessments 
The schedule of visits and assessments is provided below in . 


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Table 1. 




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4. Study Treatments 
The study treatments are as follows: 
 
LNZ101 
 
 
 
LNZ100 -
 
 
Vehicle (non-preserved) ophthalmic solution 
The two active ingredients 
 have been formulated and will be provided in a 
sterile container. 
A third solution, vehicle ophthalmic solution, will be provided for the vehicle treatment in a sterile container. 
The formulation composition will be identical to that of the 
ophthalmic solution 
except it will not contain any active ingredient. 
4.1 
Method of Assigning Subjects to Treatments  
Each subject who signs an informed consent form will be assigned a screening number. Screening numbers 
will be assigned in sequential order beginning with 001. Once a subject meets all qualification criteria, 
he/she will be randomized in a 1:1:1 ratio to one of three Latin square design sequences [(1,2,3), (2,3,1), 
and (3, 1, 2)] detailing the order in which treatments (1: LNZ101, 2: LNZ100, 3: vehicle) will be administered 
over the three study visits and will be assigned a 3-digit subject number. Subject numbers will be assigned 
in a sequential order starting at the lowest number available. No numbers will be skipped or omitted. 
Randomization will be used to avoid bias in the assignment of subjects to treatment, to increase the 
likelihood that known and unknown subject attributes (e.g., demographics and baseline characteristics) are 
evenly balanced across treatments, and to enhance the validity of statistical comparisons across 
treatments. Masked treatment will be used to reduce potential of bias during data collection and evaluation 
of clinical endpoints.  
To ensure there are 40 evaluable subjects per treatment in the modified Intent-to-Treat (mITT) population 
(defined in Section 7.1), an unmasked statistician will monitor mITT qualification criteria and provide a 
recommendation regarding how many additional subjects to enroll into the study. The unmasked statistician 
will only evaluate pre-treatment monocular BCDVA at 40 cm 
 to make recommendations 
about the number of subjects to enroll.  
A masked trained study technician will be instructed to administer the appropriate bottle of study drug 
 
 that corresponds to the assigned subject number according to the randomization list. 
4.2 
Masking and Unmasking 
An independent biostatistician who is not otherwise involved in the trial will generate the complete 
randomized study drug kit list. The subject, Sponsor, Investigators, and study staff will be masked during 
the randomization process and throughout the study. 


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In order to maintain masking to the study drug administrator and study subject, the LNZ101, LNZ100, and 
vehicle treatments will be prepared in sterile containers having an identical appearance. The sterile 
containers will be identical in size and color and have identical clinical labels (except for the subject number 
and Visit number).  
When medically necessary, the Investigator may need to determine what treatment has been assigned to 
a subject. When possible (e.g., in non-emergent situations), Ora and/or the study sponsor should be notified 
before unmasking the investigational product. A two-panel clinical label with scratch-offs will be used for 
unmasking. 
5. Sample Size and Power Considerations 
This study is expected to complete at least 40 evaluable subjects in each treatment within the mITT 
population. This sample size was informed with results from the previous Phase 2b study comparing 
Aceclidine and an Aceclidine/Tropicamide combination product to Vehicle. Power was estimated using the 
exact sign test of equality of paired proportions procedure in nQuery Advisor® 7.0 across a range of 
estimated response discordance between the treatments. The significance level of the primary analyses 
will be set at two-sided alpha levels of 0.10. The analyses will be considered descriptive and used to inform 
on future studies. 
For the primary endpoint analysis at 1-hour post-
detect a significant treatment effect, assuming at least 40% of the LNZ101 treatment subjects have at least 
a 3-line (15-letter) improvement from the pre-dose measurement of monocular BCDVA while the vehicle 
treatment has 7.5% of subjects with a 3-line improvement, assuming the non-responder concordance is at 
least 52.5%. With the same assumption on the vehicle treatment response rate (7.5%), this sample size 
LNZ101 treatment have at least a 3-line improvement, assuming non-responder concordance is at least 
60.5%. 
 
 
 
 Assuming the LNZ101 treatment maintains a response rate 
of 22%, this sample size will provide  20% power to detect a significant treatment difference at 7 hours or 
later, assuming non-responder concordance is at least 66%. 
6. Data Preparation 
6.1 
Input Data 
Study data will primarily be recorded on the electronic case report forms (eCRFs) supplied by Statistics & 
Data Corporation (SDC) using iMednet EDC (electronic data capture) system.  
When all prerequisites for database lock have been met, including availability of all masked external data, 
the database will be locked. Following database lock, approval will be obtained from the Sponsor to unmask 


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the study. Once the study has been unmasked, unmasked laboratory data will be sent to SDC. Any changes 
to the database after data have been locked can only be made with the approval of the Sponsor in 
consultation with SDC.  
Final analysis will be carried out after the following have occurred: 
 
Database lock has occurred, including receipt of all final versions of external vendor data, with 
written authorization provided by appropriate SDC and Sponsor personnel 
 
Protocol deviations have been identified and status defined (major/minor deviations) 
 
Analysis populations have been determined 
 
Randomized treatment codes have been unmasked 
6.2 
Output Data 
Data from EDC will be transferred to Biostatistics and incorporated into standard formats following the Study 
Data Tabulation Model (SDTM). Data will then be mapped to analysis datasets using the Analysis Data 
Model (ADaM).  Both SDTM- and ADaM-formatted data will be used to create the subject listings, while all 
tables and figures will be based on the ADaM-formatted data. 
SDTM will follow the SDTM version 1.4 model and will be implemented using the SDTM Implementation 
Guide version 3.3 and the SDTM Controlled Terminology version 2022-03-25. ADaM data will follow the 
ADaM version 2.1 model and will be implemented using the ADaM Implementation Guide version 1.3. Both 
SDTM and ADaM will be validated using Pinnacle 21 version 2.2. Any discrepancies in the validation will 
 
Define.xml will be created for SDTM and ADaM using the Define-XML version 2.0 model. 
7. Analysis Populations 
7.1 
Modified Intent-to-Treat 
The mITT Population consists of subjects with study eye baseline/pre-treatment monocular BCDVA at 40 
and a non-missing monocular BCDVA at 40 cm at 1 hour-post dose at each visit. 
Pairwise comparisons between treatments and changes from pre-treatment will use the mITT Population. 
Because inclusion in the mITT is assessed at each treatment visit separately it is possible subjects are 
included at some visits/treatments but not at others. Subjects who are determined to have protocol 
deviations will be reviewed by the medical monitor and/or the Chief Medical Officer of the sponsor. After 
such review the subject(s) may be removed from evaluation in the mITT if the protocol deviation is 
determined to have impacted the scientific validity of their data. 
7.2 
Intent-to-Treat 
The Intent-to-Treat (ITT) population consists of the study eye with baseline monocular BCDVA at 40 cm 
meeting the logMAR requirements listed in inclusion criteria in Section 5.2 of the protocol. All data will be 
included and no subjects will be excluded because of protocol violations/deviations. The ITT population will 


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be analyzed as randomized and will be used for the sensitivity analyses on the primary and secondary 
monocular efficacy endpoints.  
7.3 
Per Protocol 
The Per Protocol (PP) population is a subset of the ITT population and includes subjects with no major 
protocol violations/deviations likely to affect the primary efficacy endpoint. This population will be analyzed 
as treated for confirmatory and sensitivity analyses. 
7.4 
Safety 
The safety population includes all randomized subjects who receive at least one dose of study medication. 
The safety population will be analyzed as treated and will be used for the safety analyses. No data will be 
excluded for any reason. 
8. General Statistical Considerations 
8.1 
Unit of Analysis 
The unit of analysis in this study will be the study eye for all efficacy and safety summaries. The study eye 
is defined as below. 
Dynamic Study Eye: One eye per subject will be designated as the study eye at each visit. The Dynamic 
Study Eye is the eye at each visit with the highest logMAR score for baseline monocular BCDVA at 40 
cm. If both eyes have the same BCDVA at 40 cm, the study eye will be selected as the eye with the least 
hyperopic sphere (i.e., most negative value if both are negative, smallest positive value if both are 
positive, negative value if one is positive and one is negative) determined by manifest refraction within 3 
months of Visit 1 or at Visit 1. If both eyes have equal sphere, the right eye will be selected as the study 
eye. 
Additionally, non-ocular adverse events (AE) and medical history will be presented at the subject level.  
The non-study eye will be referred to as the fellow eye. Non-study eye safety summaries will also be 
presented as appropriate. 
8.2 
Missing or Inconclusive Data Handling 
In general, there will be no imputation of missing data other than for partial or missing dates where complete 
dates are required to flag data as treatment-emergent or concomitant with treatment. Partial/missing start 
and end dates for AEs and concomitant medications will be imputed as follows: 
Partial/missing start date:  
 
Dates with missing day only will be imputed as the 1st of the month unless the month and year are 
same as the month and year of first dose of study medication at each visit, in which case missing 
day will be imputed as the first dose day of study medication.  


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Dates with both day and month missing will be imputed as 1 Jan unless the year is same as the 
year of first dose of study medication at each visit, in which case missing day and month will be 
imputed as the first dose day and month of study medication. 
 
Completely missing dates will be imputed as the first dose date of study medication unless the end 
date is on or before the first dose date of study medication at each visit, in which case missing date 
will be imputed as 1 Jan of the same year as the end date. 
Partial/missing end date:  
 
Dates with missing day only will be imputed as the last day of the month unless the month and year 
are the same as the month and year of the last dose of study medication, in which case missing 
day will be imputed as the last dose day of study medication.  
 
Dates with both day and month missing will be imputed as 31 Dec unless the year is same as the 
year of the last dose of study medication, in which case missing day and month will be imputed as 
the last dose day and month of study medication.  
 
If the ongoing flag is missing or 
es  then the date will not be imputed unless death date is 
available, in which case the missing date will be imputed as the death date. If ongoing is 
o  then 
the missing end date will be imputed as the last dose date. 
 
If the imputed date is after the date of death, then the end date will be set equal to the date of 
death.  
The original dates will be displayed in data listings and the imputed dates will be used in derivations only 
(study day, treatment-emergence status, etc.). 
8.3 
Definition of Baseline 
As this is a crossover study, every subject will receive a different treatment at Visits 
. For all 
safety and efficacy analyses, baseline refers to the assessment done prior to treatment administration at 
each visit, or, if there are multiple pre-dose assessments, it is the last measurement prior to the first dose 
of study medication at each visit. Change from baseline will be calculated as follow-up visit/time point  
baseline. 
 
  
 
 
 
 
  


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8.5 
Data Analysis Conventions 
All data analysis will be performed by Statistics & Data Corporation (SDC). Statistical programming and 
analyses will be performed using SAS® version 9.4 or higher. Output will be provided in rich text format 
(RTF) for tables, and portable document format (PDF) for tables, listings, and figures using landscape 
orientation. All study data will be listed by subject, randomized sequence, visit (as applicable), and 
treatment based on all randomized subjects unless otherwise specified. 
Summaries for continuous and ordinal variables will include the number of observations (n), arithmetic 
mean, standard deviation (SD), median, minimum, and maximum. Minima and maxima will be reported with 
the same precision as the raw values; means and medians will be presented to one additional decimal 
place than reported in the raw values. Standard deviations will be presented to two additional decimal 
places than reported in the raw values. Summaries for discrete variables will include counts and 
percentages. All percentages will be rounded to one decimal place (i.e., XX.X%). Differences between 
active treatments and placebo will be calculated as active minus placebo and change from baseline will be 
calculated as follow-up visit minus baseline.  
All statistical tests will be two-sided with a significance level of 0.10 
10) unless otherwise specified. 
Confidence intervals (CI) for differences between treatments will be two-sided at 90% confidence. All 
p-values will be rounded to 4 decimal places; p-values less than 0.0001 wi
-
values greater than 0.9999 wi
.  
Unless otherwise specified, summaries will be presented by treatment and, where appropriate, visit.  
8.6 
Adjustments for Multiplicity 
There will be no adjustments for multiplicity in testing the primary efficacy endpoint at each time point at a 
distance of 40 cm in this proof of concept study. There will be also no adjustments for multiplicity for multiple 
treatments and multiple comparisons to vehicle. 
9. Disposition of Subjects 
Subject disposition will be presented in terms of the numbers and percentages of subjects who were 
randomized by cohort and total, completed the study by visit and total, and discontinued from the study. 
Disposition will be summarized by treatment sequence for all randomized subjects. 
The number of subjects in ITT, PP, and Safety analysis populations will be displayed by treatment 
sequence. Percentages of number of subjects will be calculated using randomized subjects as the 
denominator. Since inclusion to the mITT population is assessed at each visit separately, the number and 
percentage of subjects in mITT population at each visit will be presented by eye, treatment, and cohort. A 
subject listing of inclusion in each of these populations will be presented. 
The number and percentage of subjects prematurely discontinued from the study and the reasons for study 
discontinuation will be summarized by treatment sequence for all randomized subjects. The reasons for 


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study discontinuation that will be summarized include: AE, lost to follow-up, physician decision, protocol 
violation, study terminated by sponsor, withdrawal by subject, and, other. Discontinuations due to COVID-
19 will also be displayed. A subject listing will be provided which includes the date and reason for premature 
study discontinuation. 
The number and percentage of subjects with major protocol deviations will be summarized by treatment 
and overall, for all randomized subjects. Protocol deviations will be classified as major or minor prior to the 
closure of the database during a masked review of each protocol deviation. A separate table summarizing 
the number of subjects with major protocol deviations and deviation categories will be produced on the 
Safety population. 
A subject listing will be provided which includes the date of the deviation, the deviation description, the 
classification of whether the deviation was judged to be major or minor, and whether the deviation was 
COVID-19 related or not. 
In addition, subject listings will include randomization/treatment sequence (actual vs assigned), informed 
consent date, and exclusions from the PP population. 
10. Demographic and Pretreatment Variables 
10.1 
Demographic Variables 
The demographic variables collected in this study include age, sex, childbearing potential if female, race, 
ethnicity, and iris color. Subjects who record more than one race will be grouped into a single category 
denoted as Multi-racial in the summary table. Iris color will be presented at the eye level. Sex, race, ethnicity, 
and iris color will be presented using descriptive summary statistics with counts and percentages. Age 
(years) will be summarized, overall and by treatment sequence, using continuous descriptive statistics. Age 
will be reported in years and calculated using the following formula: 
Age = (Informed Consent Date  Date of Birth) / 365.25, truncated as an integer 
Demographic variables will be summarized for the ITT, Safety, and Per-Protocol populations by treatment 
sequence and overall, in tables. A subject listing that includes all demographic variables will be provided.  
10.2 
Pretreatment Variables 
Pretreatment variables are measured to ensure the safety and eligibility of subjects at Visit 1. Subject level 
listings of the assessments below will be used to present pretreatment information from the ITT population 
at the eye level when appropriate.  


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11. Medical History and Concomitant Medications 
11.1 
Medical History 
Medical history will be coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 25.0. 
Non-ocular medical history will be summarized using discrete summary statistics and presented by 
treatment sequence at the subject level by System Organ Class (SOC) and Preferred Term (PT) using the 
ITT and Safety Populations. Ocular medical history will be similarly summarized at the subject level. If a 
subject reports the same PT multiple times within the same SOC, that PT will only be reported once within 
that SOC. As with the PT, if a subject reports multiple conditions within the same SOC, that SOC will only 
be reported once. 
Tables and listings of medical history will be generated separately for ocular and non-ocular data. 
11.2 
Concomitant Medications 
and summarized to the therapeutic drug class (Anatomical Therapeutic 
Chemical [ATC] 4 classification) and preferred name. If the ATC 4 classification is not provided, then the 
next highest classification that is provided in the coding dictionary will be used. The preferred name will be 
defined as the active ingredient; if the active ingredient is not provided or includes more than two ingredients 
(e.g., multivitamins), then the drug name will be summarized as the preferred name. Any uncoded terms 
 
 
medications will be summarized 
Medications will be tabulated for 
each treatment using frequencies and percentages. 
listings of 
will be generated separately for ocular and non-ocular data. 
12. Dosing Compliance and Treatment Exposure 
12.1 
Dosing Compliance 
As this is a single dose study and the study drug will be administered by a trained study technician at each 
visit; therefore, dosing compliance and exposure will not be calculated. Treatment administration will be 
listed by subject. 


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13. Efficacy Analyses 
13.1 
Primary Analysis 
The primary efficacy variable in this study is the percentage of subjects with at least a 3-line (15-letter) 
improvement from the pre-dose measurement of 
 monocular BCDVA at 40 cm and 
no loss in BCDVA  5 letters (ETDRS chart at 4 m) 
. Primary 
analysis will use the population as described in Section 7.1. The primary analyses will separately compare 
the LNZ101 treatment versus the vehicle treatment 
 
 
Counts and percentages of subjects who meet the primary efficacy criteria described above will be 
presented by treatment for the study eye. Inferential testing of the percentage of subjects who meet the 
primary efficacy criteria above will be completed by generating an odds ratio (along with 80% and 90% CIs 
and p-value) from a logistic model (binomial error and logit link) estimated by generalized estimating 
equation (GEE) methods. This model accounts for the correlations between treatments and visits within a 
subject. Aspects of the model include: 
 
Response Measure: Indicator of whether the subject had at least a 3-line (15-letter) improvement 
 from pre-dose in the monocular assessment of BCDVA at 40 cm and no loss in 
 m). 
 
Fixed effect explanatory measures: sequence, visit, and treatment. 
 
Repeated measures correlation will be estimated with an unstructured variance-covariance matrix 
in the GEE model. If the model fails to converge, alternative covariance structures, such as AR(1), 
Toeplitz, or compound symmetry, will be tried in the order specified. 
Example SAS® code is shown here: 
 
 = option that specifies that 1 is a yes and 0 is a no (NOTE: SAS® default is ascending) 
 
 = option specifies the family-wise error rate, default is .05. (NOTE: code will be run with 
both .05 and .1 for confidence interval output) 
 
= treatment sequence  
 
= visit number (Visits 2, 3, and 4) 
 
= treatment / study drug 


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 = indicator for the efficacy variable, (  3-line improvement in BCDVA at 40 cm and no loss in 
= 1 or < 3-line improvement in BCDVA at 40 cm and no loss in BCDVA 
= 0) 
 
 = the error term as a binomial distribution with a logit link (Note: SAS® default is link =
 when 
)  
The proportion of subjects meeting the primary efficacy criteria in each treatment for the study eye will also 
be analyzed using 
homogeneity and the p-value for this test will 
be reported. 
® is: 
Note that the 
 statement 
will need to include pairs of treatments 
(
, 
) with counts of responders and non-responders. The primary endpoint will also be 
analyzed on the ITT and PP populations.  


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15. Safety Analyses 
All safety analyses will be conducted using the safety population. 
15.1 
Adverse Events 
An AE is defined as any untoward medical occurrence associated with the use of an investigational product 
(IP) in humans, whether or not the event is considered IP-related. An AE can therefore be any unfavorable 
and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with 
the use of an IP, without any judgment about causality. An AE can arise from any use of the IP (e.g., off-
label use, use in combination with another drug or medical device) from any route of administration, 
formulation, or dose, including an overdose. Any pre-existing medical condition that worsens after first 
administration of the study drug will also be considered a new AE. The AE reporting period ends upon study 
exit. Investigational product includes the investigational drug under evaluation and vehicle given during any 
stage of the study. All AEs will be coded using MedDRA Version 25.0.  
Treatment-emergent adverse events (TEAEs) are defined as any event that occurs or worsens on or after 
the first dose of study drug instillation. A TEAE for a treatment is defined as an AE that started or worsened 
on or after that specific treatment administration and before the administration of subsequent treatment or 
study completion/discontinuation.. Adverse events recorded in the eCRF which began prior to the first 
treatment will not be included in the summary tables but will be included in the AE data listings. 
Severity of an AE is defined as a qualitative assessment of the degree of intensity of an AE as determined 
by the Investigator or reported to him/her by the subject. The assessment of severity is made irrespective 
of relationship to the IP or seriousness of the event and should be evaluated according to the following 
scale: 


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Mild: Event is noticeable to the subject, but is easily tolerated and does not interfere with the 
 
 
Moderate: Event is bothersome, possibly requiring additional therapy, and may interfere with the 
 
 
Severe: Event is intolerable, necessitates additional therapy or alteration of therapy, and interferes 
 
The relationship of each AE to the IP is determined by the Investigator using these explanations: 
 
Suspected: A reasonable possibility exists that the IP caused the AE. 
 
Not Suspected: A reasonable possibility does not exist that the IP caused the AE. 
The expectedness of an AE is determined based upon existing safety information about the IP these 
explanations: 
 
specificity or severity that has been observed. 
 
Expected: an AE that is listed in the IB at the specificity and severity that has been observed. 
 
Not applicable: an AE unrelated to the IP. 
An overall summary will be presented that includes the number of events and the number and percentage 
of subjects who experienced at least one TEAE, by treatment and overall for all subjects. This summary 
will also include breakdowns of TEAEs further categorized as ocular (study eye and fellow eye separately) 
or non-ocular, treatment-related TEAEs, treatment-emergent serious adverse events (SAEs), TEAEs 
leading to early treatment discontinuation, TEAEs leading to death, and TEAEs (ocular and non-ocular) by 
maximum severity. 
The following summaries will be presented by treatment, SOC, and PT. If a subject reports the same PT 
multiple times within the same SOC, that PT will only be reported once within that SOC. As with the PT, if 
a subject reports multiple conditions within the same SOC, that SOC will only be reported once. In the 
summaries, SOCs will be listed in alphabetical order; PTs will be listed in order of descending frequency 
for all subjects within each SOC. 
 
Ocular TEAEs 
 
Non-ocular TEAEs  
 
Treatment-related ocular TEAEs 
 
Treatment-related non-ocular TEAEs.  
 
Expected TEAEs 
 
Unexpected TEAEs 
 
Treatment-Emergent SAEs 


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Summaries of TEAEs by maximum severity will be presented for ocular AEs and non-ocular AEs separately. 
The number of subjects with any TEAEs (along with percentages) will be tabulated by SOC and PT within 
each SOC by treatment. To count the number of subjects with any TEAEs, if a subject has multiple TEAEs 
coded to the same PT within the same SOC, the subject will be counted once under the maximum severity. 
All AEs will be presented in a subject listing. The AEs leading to study treatment discontinuation will be 
listed separately. In addition, all SAEs will be presented in a separate listing. 
15.2 
BCDVA at 40 cm in Letter Score 
The observed and change from baseline in monocular and binocular BCDVA letter score at 40 cm at every 
scheduled visit at all post-treatment time points
 will be summarized 
in tables by treatment and eye using the Safety population.  
15.3 
Low-Luminance BCDVA  
Monocular and binocular low-luminance BCDVA using an ETDRS chart calibrated for testing at 4 meters 
will be conducted 
. Results will be recorded 
in logMAR units.  
The observed and change from baseline low-luminance BCDVA will be summarized for each eye (study 
eye and fellow eye for monocular low-luminance BCVA) and both eyes (for binocular low-luminance BCVA) 
using continuous descriptive statistics by time point for each treatment. A subject listing of low-luminance 
BCDVA will also be produced.  
15.4 
Slit Lamp Biomicroscopy Examination and Dilated Fundoscopy 
A slit lamp biomicroscopy examination will be conducted on both eyes at all scheduled visits and at the 
last time point for each visit in the eyelid, conjunctiva, cornea, anterior chamber, iris, and lens. The results 
will be graded as normal, not clinically significant (NCS), or clinically significant (CS). 
A table will summarize results using counts and percentages for each treatment at each time point and 
location for each eye. Percentages will be based on the number of subjects in each treatment with 
responses. Shift tables and subject-level listings will also be provided. 
15.5 
Conjunctival Hyperemia  
Conjunctival hyperemia is measured 
 Conjunctival redness will be summarized by treatment, for the study and fellow eye separately, 
using continuous descriptive summary statistics in a table. Change from baseline will also be calculated 
and summarized using descriptive summary statistics in a table. The data for conjunctival redness will be 
presented in a listing. 


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15.6 
Intraocular Pressure  
Intraocular pressure is measured 
 Observed IOP values 
will be summarized by treatment, for the study and fellow eye separately, using continuous descriptive 
summary statistics in a table. The data for IOP examinations will be presented in a subject listing. 
15.7 
Urine Pregnancy Test 
Female subjects of childbearing potential will have a urine pregnancy test at the site at each visit. A subject 
level listing by visit will be produced. 
16. Other Analyses 
16.1 
Patient Reported Outcome Questionnaire  
Subjects will be required to answer Patient Reported Outcome (PRO) questionnaire
 
. Counts and proportions for the responses to the following questions will be 
presented by treatment on the mITT and Safety Population. 
1.
 
 
 
 
 
 
 
 
 
 
 
 
  
16.2 
Monocular and Binocular Uncorrected Distance Visual Acuity 
Monocular and binocular uncorrected distance VA at 4 m will be collected 
 The observed and change from baseline logMAR values from these 
assessments will be summarized in tables by treatment and eye using the safety population. A subject 
listing of monocular and binocular uncorrected distance VA will also be produced. 
16.3 
Drop Instillation Assessment 
 
 
 
 
 
 
  




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