A Study of the Efficacy and Tolerability of Pancrelipase Microtablet (MT) Capsules for the Treatment of Cystic Fibrosis-dependent Exocrine Pancreatic Insufficiency
A Study of the Efficacy and Tolerability of Pancrelipase Microtablet (MT) Capsules for the Treatment of Cystic Fibrosis-dependent Exocrine Pancreatic Insufficiency
The purpose of this study is to assess the effectiveness and safety of oral pancrelipase MT
 in the treatment of adult and pediatric/adolescent cystic fibrosis (CF) patients with
 clinical symptoms of exocrine pancreatic insufficiency (EPI).
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 children/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 withdrawl phase. The study
 including the screening phase will be approximately 28 days in length. In the screening
 phase, patients will begin a high-fat diet and will take pancrelipase MT10.5 or MT21 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. Safety will be
 montitored during the study by evaluating adverse events and findings from clinical
 laboratory tests, vital signs measurements, and physical examinations. 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 MT10.5 or MT21 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 lipase units 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.
Inclusion Criteria:

 -  Have a diagnosis of CF documented by sweat chloride results (>60 mmol/L) and require
 pancreatic enzyme replacement therapy (PERT) to control clinical symptoms of EPI
 (nausea, vomiting, bloating, diarrhea, and abdominal pain) with a history of excess
 fat in the feces

 -  Have documentation of an abnormal COA-fat and a fecal elastase result of <100
 micrograms fecal elastase/gram stool

 -  Must be on a stable diet and dose of pancreatic enzyme supplementation that has
 provided satisfactory symptom control for at least the past 1 month

 Exclusion Criteria:

 -  No extreme physical wasting with loss of weight and muscle mass

 -  No severe, acute, or chronic pulmonary disease unrelated to complications of CF

 -  No worsening of pulmonary disease in past 30 days

 -  No use of drugs known to affect blood uric acid concentrations (e.g., aspirin,
 diflunisal, allopurinol, probenecid, thiazide diuretics, phenylbutazone,
 sulfinpyrazone)

 -  No known congenital (present at birth) abnormalities of the gastrointestinal tract,
 heart, or liver

 -  No distal intestinal obstruction syndrome (DIOS)