• The change in COA-fat (percentage) from the 72-hour stool collection period at the end of the open-label phase to the 72-hour stool collection period at the end of the double-blind withdrawal phase. [ Time Frame: 72-hours stool collection in the open-label phase to the end of 72-hours stool collection in the double-blind withdrawal phase. ] [ Designated as safety issue: No ]
  

• The change in COA-protein from the stool collection period in double-blind phase to open-label phase; the change in number of bowel movements and stool consistency from the 72-hour inpatient period in open-label phase to double-blind phase. [ Time Frame: 72-hours stool collection in the open-label phase to the end of 72-hours stool collection in the double-blind withdrawal phase. ] [ Designated as safety issue: No ]
  

This is a randomized, placebo-controlled, double-blind withdrawal, multicenter study to evaluate the effectiveness of pancrelipase MT capsules compared with placebo in the treatment of adult (>18 to 60 years of age) and pediatric/adolescent (7 to 18 years of age) patients with CF and who require pancreatic enzyme replacement therapy (PERT) to control clinical symptoms of EPI and steatorrhea (excess fat in the feces). The study has 3 phases: a screening phase, an open-label (run-in) phase, and a double-blind withdrawal phase. The study including the screening phase will be approximately 21 days in length. In the screening phase, patients will begin a high-fat diet and will take pancrelipase MT10 or MT20 capsules (or a combination of both) orally with meals (or snacks) to optimize digestion based on clinical signs and symptoms. In the open-label phase patients will continue taking their optimal dose of study drug. After a minimum of 3 days in the open-label treatment phase, an inpatient 72-hour stool collection period for fecal fat determination will be performed.

Patients with a coefficient of fat absorption (COA)-fat of 80% or greater who have completed at least 6 days on a controlled high-fat diet will be eligible for the double-blind withdrawal phase of the study and will be randomly assigned to receive placebo or pancrelipase MT. After a minimum of 1 day on double-blind treatment and with the presence of deteriorating clinical signs and symptoms, patients will be admitted to the clinic to begin a second 72-hour inpatient stool collection period. Effectiveness evaluations will be performed throughout the study and consist of stool collection for determination of COA-fat and coefficient of protein absorption (COA-protein), stool diary, nutrition worksheet, and Clinical Global Impression-Severity of illness (CGI-S), Clinical Global Impression-Change (CGI-C), and Global Assessment of Change (GAC) scales. Signs and symptoms exhibited during the study will be monitored and will include the presence or absence of diarrhea, abdominal pain, nausea, vomiting, bloating, and a description of stool changes. The study hypothesis is that the study drug will be more effective than placebo as measured by the change in the coefficient of fat absorption (COA-fat) in adults and pediatric/adolescent patients with EPI secondary to CF.

Pancrelipase MT10 or MT20 capsules (or a combination of both) will be taken orally with meals (or snacks) within the recommended ranges of pancreatic enzyme therapy as recommended by the CF Foundation and up to a maximum 10,000 units lipase per kilogram [kg] per day. All patients will take pancrelipase MT for 6 days in the screening phase and for approximately 6 to 10 days in the open-label phase; patients will take pancrelipase MT or placebo for 4 to 7 days in the double-blind phase.