Clinical trial NCT00662675: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Exocrine Pancreatic Insufficiency
Steatorrhea
Malabsorption Syndromes
Cystic Fibrosis
Keywords: Exocrine pancreatic insufficiency
Steatorrhea
Malabsorption syndromes
Cystic fibrosis
Pediatrics
Adult
Pancrelipase
Lead sponsor: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Sponsor class: INDUSTRY
First posted: 2008-04-21
Enrollment: 40
Sex: ALL
Minimum age (years): 7
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility 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)

Primary outcomes:
measure: Change in the Coefficient of Fat Absorption (COA-fat Percent)
timeFrame: 72-hours stool collection in the open-label phase to the end of 72-hours stool collection in the double-blind withdrawal phase.
Secondary outcomes:
measure: Change in Percent COA-Protein (Nitrogen)
timeFrame: 72-hours stool collection in the open-label phase to the end of 72-hours stool collection in the double-blind withdrawal phase.
measure: Percent of Patients Reporting Clinical Signs and Symptoms of Exocrine Pancreatic Insufficiency (EPI) During the Double-Blind Phase
timeFrame: Entire 7 days double-blind phase
Other outcomes:
Locations:
city: Long Beach
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Orlando
country: United States
state: Florida
city: Louisville
country: United States
state: Kentucky
city: Las Vegas
country: United States
state: Nevada
city: Long Branch
country: United States
state: New Jersey
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Oklahoma City
country: United States
state: Oklahoma
city: Pittsburgh
country: United States
state: Pennsylvania
city: Vancouver N/A
country: Canada
state: British Columbia
Study officials:
affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
name: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial
role: STUDY_DIRECTOR
References: