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

Study Description

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Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Exocrine Pancreatic Insufficiency; Steatorrhea; Malabsorption Syndromes; Cystic Fibrosis	Drug: Pancrease MT 10.5, or MT 21; Drug: Placebo for Pancrease MT 10.5 or MT 21	Phase 3

Detailed Description:

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	40 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
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
Study Start Date :	August 2008
Actual Primary Completion Date :	February 2009
Actual Study Completion Date :	February 2009

Arms and Interventions

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

Outcome Measures

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Primary Outcome Measures :

1. 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. ]
   Change in the coefficient of fat absorption (percent COA-fat) from the 72-hour inpatient period in the open-label phase to the 72-hour period inpatient period in the double-blind (withdrawal) phase.

Secondary Outcome Measures :

1. 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. ]
   The change in percent COA-protein from the stool collection period in double-blind phase to open-label phase
2. 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 ]
   Percent of patients reporting nausea, vomiting, bloating, diarrhea, oily/greasy stools, and abdominal pain signs and symptoms reported as Adverse events during the double-blind phase.

Eligibility Criteria

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Ages Eligible for Study:	7 Years to 60 Years (Child, Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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)

Contacts and Locations

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Locations

United States, California
Long Beach, California, United States
Los Angeles, California, United States
United States, Florida
Orlando, Florida, United States
United States, Kentucky
Louisville, Kentucky, United States
United States, Nevada
Las Vegas, Nevada, United States
United States, New Jersey
Long Branch, New Jersey, United States
United States, Ohio
Cincinnati, Ohio, United States
Cleveland, Ohio, United States
United States, Oklahoma
Oklahoma City, Oklahoma, United States
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States
Canada, British Columbia
Vancouver N/A, British Columbia, Canada

Sponsors and Collaborators

Johnson & Johnson Pharmaceutical Research & Development, L.L.C.

Investigators

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

More Information

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Additional Information:

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 

Responsible Party:	Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:	NCT00662675 History of Changes
Other Study ID Numbers:	CR014719
First Posted:	April 21, 2008
Results First Posted:	March 17, 2010
Last Update Posted:	May 9, 2014
Last Verified:	April 2014

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Exocrine pancreatic insufficiency; Steatorrhea; Malabsorption syndromes; Cystic fibrosis	Pediatrics; Adult; Pancrelipase

Additional relevant MeSH terms:

Fibrosis; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Malabsorption Syndromes; Steatorrhea; Pathologic Processes; Pancreatic Diseases; Digestive System Diseases; Lung Diseases	Respiratory Tract Diseases; Genetic Diseases, Inborn; Infant, Newborn, Diseases; Intestinal Diseases; Gastrointestinal Diseases; Metabolic Diseases; Pancrelipase; Pancreatin; Gastrointestinal Agents