Clinical trial NCT00981214: Study of Pancreatic Enzyme Product in Pediatric Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
Official title: An Open-Label Study to Evaluate the Efficacy and Safety of Pancreatic Enzyme Product (PEP) Microtabs in Pediatric Patients With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Exocrine Pancreatic Insufficiency
Keywords: Cystic fibrosis
Exocrine Pancreatic Insufficiency
Zenpep-1009
Lead sponsor: Forest Laboratories
Sponsor class: INDUSTRY
First posted: 2009-09-22
Enrollment: 19
Sex: ALL
Maximum age (years): 7
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label study to evaluate the efficacy and safety of Aptalis' (formerly Eurand) pancreatic enzyme product (PEP) microtabs in pediatric participants under age 7 with cystic fibrosis (CF) and exocrine pancreatic insufficiency (EPI).

Detailed description: The study sample will consist of evaluable participants, all of whom will be children younger than 7 years of age. Participants will receive EUR-1008 (APT-1008) Microtabs formulation. The study design involves a 4-day screening period, a 7-day dose stabilization period, and a 7-day treatment period (excluding an end-of-study evaluation).

The optimal dose of EUR-1008 (APT-1008) Microtabs, determined during the dose stabilization period, will be used during the treatment period. Participants are instructed to consume a predefined diet.

Eligibility criteria: Inclusion Criteria:

* Participants less than 7 years of age
* Participants who have pancreatic insufficiency documented by a fecal elastase level less than 100 micrograms per gram (mcg/g), or if not documented, the fecal elastase test must be done at the screening visit
* Participants who have a need of de novo treatment with pancreatic enzymes or be able to be switched from an existing treatment
* Participants who have a body mass index greater than the twenty fifth percentile for children 2 years and older
* Participants with a weight for height index greater than the twenty fifth percentile for children less than 2 years of age
* Participants with diagnosis of CF based upon the following criteria:

  * Have 2 clinical features consistent with CF and
  * Have either a genotype with 2 identifiable mutations consistent with CF or a sweat chloride concentration that is more than 60 milliequivalent per liter (mEq/L) by quantitative pilocarpine iontophoresis
* Participants who are clinically stable with no evidence of acute upper or lower respiratory tract infection

Exclusion Criteria:

* Participants with fibrosing colonopathy
* Participants allergic to pork or other porcine PEPs
* Participants with any respiratory condition that in the investigator's opinion would result in an intervention requiring hospitalization or intensive pulmonary treatment during the trial
* Participants with any acute systemic administration of an antibiotic for any reason in the previous 4 weeks; however, a low stable dose of an antibiotic (such as azithromycin 250 or 500 milligram \[mg\] up to 3 times per week) is allowed. Moreover, chronic treatment (that is, daily for at least 1 month) with an inhalatory antibiotic (for example, colistin, tobramycin, or ceftazidime) is allowed
* Participants who have hepatic insufficiency as defined by a history or presence of ascites, or a serum albumin level of less than 3.0 milligram per deciliter (mg/dL), or coagulopathy with an international normalized ratio that is greater than 1.7
* Participants with hyperuricemia or hyperuricosuria
* Participants participating in an investigational study of a drug, biologic, or device not currently approved for marketing within 30 days prior to screening visit
* Participants with history of or current screening evaluation of hyperglycemia as defined by an 8-hour fasting serum glucose equivalent to 126 mg/dL or more, or of cystic-fibrosis-related diabetes as determined according to the Cystic Fibrosis Foundation (CFF) Consensus Conference of January 1999 (Section IX Part II), that is:

  * Fasting Blood Glucose (FBG) greater than126 mg/dl (7.0 milli mole \[mM\]) on two or more occasions
  * FBG greater than 126 mg/dl (7 .0 mM) plus casual (without regard to time of day or last meal consumed) glucose level greater than200 mg/dl (11.1 mM)
  * Casual (previously called random) glucose levels greater than 200 mg/dl (11.1 mM) on two or more occasions with symptoms
* Participants with any solid organ transplant or surgery affecting the bowel
* Participants using an enzyme preparation in excess of 10,000 lipase units/kg/day
* Participants with an acute dose of any steroid in the previous 2 weeks; however, low chronic doses of a steroid (less 0.5 mg/kg every other day) will be allowed
* Participants with any condition that would, in the investigator's opinion, limit the patient's ability to complete the study
* Participants with history of or current screening determination of distal ileal obstruction syndrome (DIOS), or any clinical signs and symptoms suggestive of DIOS (that is, constipation, abdominal pain, anorexia, early satiety, recurrent vomiting and palpable fecal mass) on physical examination
* Participants who are unable to discontinue excluded concomitant medications over the course of the study

Primary outcomes:
measure: Percentage of Participants Who Were Responders After 1 Week of Treatment With Study Medication
timeFrame: Day 11
measure: Percentage of Participants Who Were Responders After 2 Weeks of Treatment With Study Medication
timeFrame: Day 18 (end of treatment)
Secondary outcomes:
measure: Change From Baseline in Weight at Day 12, 19
timeFrame: Baseline, Day 12, 19
measure: Mean Daily Number of Stools
timeFrame: Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)
measure: Percentage of Stool Categorized by Consistency
timeFrame: Baseline, Day 5 up to Day 11 (dose stabilization period) and Day 12 up to Day 18 (treatment period)
measure: Mean Number of Abdominal Symptoms: Bloating
timeFrame: Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)
measure: Mean Number of Abdominal Symptoms: Flatulence
timeFrame: Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)
measure: Mean Number of Pain Symptoms
timeFrame: Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)
measure: Physician's and Parent's or Legal Guardians Assessment of Improvement in Clinical Symptoms
timeFrame: Day 19 (end of study)
measure: Percentage of Blood in Stool
timeFrame: Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)
measure: Percentage of Stool With Visible Oil or Grease
timeFrame: Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Oakland
country: United States
facility: Children's Hospital - Oakland
state: California
city: Palo Alto
country: United States
facility: Stanford University Medical Center
state: California
city: San Diego
country: United States
facility: Children's Hospital of San Diego
state: California
city: Gainsville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Jacksonville
country: United States
facility: Nemours Childrens Clinic
state: Florida
city: Chicago
country: United States
facility: Childrens Memorial Hospital
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa
state: Iowa
city: Ann Arbor
country: United States
facility: University of Michigan, Cystic Fibrosis Center
state: Michigan
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center
state: Ohio
city: Tyler
country: United States
facility: University of Texas
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Morgantown
country: United States
facility: West Virginia Health Sciences Center
state: West Virginia
Study officials:
affiliation: Forest Laboratories
name: Aptalis Medical Information
role: STUDY_DIRECTOR
References: