The incidence of adverse events (regardless of causality) was similar during double blind ZENPEP treatment (56%) and placebo treatment (50%). The most common adverse events reported during the study were gastrointestinal complaints, which were reported more commonly during placebo treatment (41%) than during ZENPEP treatment (32%), and headache, which was reported more commonly during ZENPEP treatment (15%) than during placebo treatment (0). The type and incidence of adverse events were similar in children (7-11 years), adolescents (12-16 years), and adults (greater than 18 years).

Because clinical trials are conducted under controlled conditions, the observed adverse event rates may not reflect the rates observed in clinical practice.

Table 1 enumerates treatment-emergent adverse events that occurred in at least 2 patients (greater than or equal to 6%) treated with either ZENPEP or placebo in Study 1. Adverse events were classified by Medical Dictionary for Regulatory Activities (MedDRA) terminology.

Table 1: Treatment-Emergent Adverse Events Occurring in at least 2 Patients (greater than or equal to 6%) During Treatment Period and Crossover Treatment Period of the Placebo-Controlled, Crossover Clinical Study of ZENPEP (Study 1)

MedDRA Primary System Organ Class Preferred Term ZENPEP
(N=34) % Placebo
(N=32) %
Gastrointestinal Disorders    
   Abdominal pain 6 (18%) 9 (28%)
   Flatulence 2 (6%) 3 (9%)
Nervous System Disorders    
   Headache 5 (15%) 0
Injury, Poisoning and Procedural Complications    
   Contusion 2 (6%) 0
Investigations    
   Weight decreased 2 (6%) 2 (6%)
Respiratory, Thoracic and Mediastinal Disorders    
   Cough 2 (6%) 0
General Disorders and Administration Site Conditions    
   Early Satiety 2 (6%) 0

Study 2 was an open-label, uncontrolled study of 19 patients, ages 1 to 6 years, with EPI due to CF. After a 4-14 days screening period on the current PEP, patients in Study 2 received ZENPEP at individually titrated doses ranging between 2,300 and 10,000 lipase units per kg body weight per day, with a mean of approximately 5000 lipase units per kg body weight per day (not to exceed 2,500 lipase units per kilogram per meal) for 14 days. There was no comparator treatment, and adverse events were collected on patient diary entries and at each study visit.

The most commonly reported adverse events were gastrointestinal, including abdominal pain and steatorrhea, and were similar in type and frequency to those reported in the double-blind, placebo-controlled trial (Study 1).

6.2 Postmarketing Experience
There is no postmarketing experience with this formulation of ZENPEP.

Delayed- and immediate-release pancreatic enzyme products with different formulations of the same active ingredient (pancrelipase) have been used for the treatment of patients with exocrine pancreatic insufficie