A Study of the Efficacy and Tolerability of Pancrelipase Microtablet (MT) Capsules for the Treatment of Cystic Fibrosis-dependent Exocrine Pancreatic Insufficiency

Official Title: “A Randomized Double-blind (Withdrawal) Phase 3 Study to Evaluate the Efficacy and Tolerability of Pancrelipase MT Capsules Compared With Placebo in the Treatment of Subjects With 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.

Intervention(s) in this Clinical Trial

• Drug: Pancrease MT 10.5, or MT 21
  • Pancrease MT capsules for maximum dose of 10,000 lipase units / Kg / day
• Drug: Placebo for Pancrease MT 10.5 or MT 21
  • Capsules with Pancrease MT excipients without the active enzymes

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 001
  • Pancrease MT 10.5 or MT 21 Pancrease MT capsules for maximum dose of 10 000 lipase units / Kg / day
• Experimental: 002
  • Placebo for Pancrease MT 10.5 or MT 21 Capsules with Pancrease MT excipients without the active enzymes

Primary Measures

• Change in the Coefficient of Fat Absorption (COA-fat Percent)
  • 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.
    Safety Issue?: No

Secondary Measures

• Change in Percent COA-Protein (Nitrogen)
  • 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.
    Safety Issue?: No
• Percent of Patients Reporting Clinical Signs and Symptoms of Exocrine Pancreatic Insufficiency (EPI) During the Double-Blind Phase
  • Time Frame: Entire 7 days double-blind phase
    Safety Issue?: No

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)

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 7 Years

Maximum Age for this Clinical Trial: 60 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Industry

Overall Clinical Trial Officials and Contacts

Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Study Director Johnson & Johnson Pharmaceutical Research & Development, L.L.C.  

Information obtained from ClinicalTrials.gov on February 09, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00662675

Study ID Number: CR014719

ClinicalTrials.gov Identifier: NCT00662675

Health Authority: United States: Food and Drug Administration

A randomized double-blind (withdrawal) Phase 3 study to evaluate the efficacy and tolerability of PANCREASE MT capsules compared with placebo in the treatment of subjects with cystic fibrosis-dependent exocrine pancreatic insufficiency