Study of Pancreatic Enzyme Product in Pediatric Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Aptalis Pharma
ClinicalTrials.gov Identifier:
NCT00981214
First received: September 21, 2009
Last updated: February 24, 2014
Last verified: February 2014
  Purpose

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).


Condition Intervention Phase
Cystic Fibrosis
Exocrine Pancreatic Insufficiency
Drug: EUR-1008 (APT-1008)
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Aptalis Pharma:

Primary Outcome Measures:
  • Percentage of Participants Who Were Responders After 1 Week of Treatment With Study Medication [ Time Frame: Day 11 ] [ Designated as safety issue: No ]
    Responders were defined as those participants without steatorrhea (defined as less than 30 percent (%) fecal fat content) and without signs and symptoms of malabsorption after 1 week of treatment with study medication.

  • Percentage of Participants Who Were Responders After 2 Weeks of Treatment With Study Medication [ Time Frame: Day 18 (end of treatment) ] [ Designated as safety issue: No ]
    Responders were defined as those participants without steatorrhea (defined as less than 30% fecal fat content) and without signs and symptoms of malabsorption after 2 weeks of treatment with study medication.


Secondary Outcome Measures:
  • Change From Baseline in Weight at Day 12, 19 [ Time Frame: Baseline, Day 12, 19 ] [ Designated as safety issue: No ]
  • Mean Daily Number of Stools [ Time Frame: Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period) ] [ Designated as safety issue: No ]
    Mean daily number of stools of each participant was calculated from frequency of stools by the participant per day. Mean daily number of stools at each period for total participants was summarized.

  • Percentage of Stool Categorized by Consistency [ Time Frame: Baseline, Day 5 up to Day 11 (dose stabilization period) and Day 12 up to Day 18 (treatment period) ] [ Designated as safety issue: No ]
    Stool consistency was categorized as hard, formed/normal, soft, watery or overt diarrhea. Percentage of stools of a specific consistency of each participant was calculated as the number of stools with a specific consistency relative to the total number of stools during the collection period. Mean percentage of stool with specific consistency at each period for total participants was summarized.

  • Mean Number of Abdominal Symptoms: Bloating [ Time Frame: Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period) ] [ Designated as safety issue: No ]
    Bloating is swelling of the intestinal tract caused by excessive gas formation. Symptoms of bloating were classified by severity as mild (no impairment of daily activities), moderate (slight impairment of daily activities), or severe (unable to perform daily activities). Mean number of symptoms of specific severity for each participant was calculated from frequency of symptoms by the participant per day. Mean number of symptoms at each period for total participants was summarized.

  • Mean Number of Abdominal Symptoms: Flatulence [ Time Frame: Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period) ] [ Designated as safety issue: No ]
    Flatulence is presence of excessive gas in the digestive tract. Symptoms of flatulence was classified by severity as mild (no impairment of daily activities), moderate (slight impairment of daily activities), or severe (unable to perform daily activities). Mean number of symptoms of specific severity for each participant was calculated from frequency of symptoms by the participant per day. Mean number of symptoms at each period for total participants was summarized.

  • Mean Number of Pain Symptoms [ Time Frame: Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period) ] [ Designated as safety issue: No ]
    Symptoms of pain was classified by severity as mild (no impairment of daily activities), moderate (slight impairment of daily activities), or severe (unable to perform daily activities). Mean number of symptoms of specific severity for each participant was calculated from frequency of symptoms by the participant per day. Mean number of symptoms at each period for total participants was summarized.

  • Physician's and Parent's or Legal Guardians Assessment of Improvement in Clinical Symptoms [ Time Frame: Day 19 (end of study) ] [ Designated as safety issue: No ]
    Clinical symptoms of exocrine pancreatic insufficiency (EPI) were assessed by the physician and parent or guardian to determine if the participant showed improvement in symptoms of EPI at end of study after the dose stabilization period. EPI is a syndrome characterized by clinical symptoms of poor absorption of fats, proteins, and to a lesser extent, carbohydrates, which manifests primarily in patients with cystic fibrosis. Number of participants with improvement in clinical symptoms was reported.

  • Percentage of Blood in Stool [ Time Frame: Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period) ] [ Designated as safety issue: No ]
    Mean percentage of stools with blood at each period for total participants was summarized.

  • Percentage of Stool With Visible Oil or Grease [ Time Frame: Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period) ] [ Designated as safety issue: No ]
    Mean percentage of oil or grease at each period for total participants was summarized.


Enrollment: 19
Study Start Date: May 2006
Study Completion Date: September 2006
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EUR-1008 (APT-1008) Drug: EUR-1008 (APT-1008)
EUR-1008 (APT-1008) Microtabs contained in a capsule will be administered orally from Day 5 to Day 11 at an enzyme dose based on investigator's discretion, in dose stabilization period or the content of the capsule will be allowed to sprinkle on food, where necessary, followed by stabilized dose from Day 12 to Day 18 in treatment period, up to a maximum total dose of 10,000 lipase units per kilogram body weight per day (unit/kg/day).
Other Names:
  • ZENPEP®
  • Pancrelipase

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

Ages Eligible for Study:   up to 7 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00981214

Locations
United States, Alabama
University of Alabama
Birmingham, Alabama, United States, 35294
United States, California
Children's Hospital of Los Angeles
Los Angeles, California, United States, 90027
Children's Hospital - Oakland
Oakland, California, United States, 94609
Stanford University Medical Center
Palo Alto, California, United States, 94304
Children's Hospital of San Diego
San Diego, California, United States, 92123
United States, Florida
University of Florida College of Medicine
Gainsville, Florida, United States, 32610-0296
Nemours Childrens Clinic
Jacksonville, Florida, United States, 32250
United States, Illinois
Childrens Memorial Hospital
Chicago, Illinois, United States, 60614
United States, Iowa
University of Iowa
Iowa City, Iowa, United States, 52242
United States, Michigan
University of Michigan, Cystic Fibrosis Center
Ann Arbor, Michigan, United States, 48109
United States, Ohio
Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
United States, Texas
University of Texas
Tyler, Texas, United States, 75708
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84108
United States, West Virginia
West Virginia Health Sciences Center
Morgantown, West Virginia, United States, 26506
Sponsors and Collaborators
Aptalis Pharma
Investigators
Study Director: Aptalis Medical Information Aptalis Pharma
  More Information

No publications provided

Responsible Party: Aptalis Pharma
ClinicalTrials.gov Identifier: NCT00981214     History of Changes
Other Study ID Numbers: EUR-1009-M
Study First Received: September 21, 2009
Results First Received: February 24, 2014
Last Updated: February 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Aptalis Pharma:
Cystic fibrosis
Exocrine Pancreatic Insufficiency
Zenpep-1009

Additional relevant MeSH terms:
Cystic Fibrosis
Fibrosis
Exocrine Pancreatic Insufficiency
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Pathologic Processes
Pancrelipase
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 17, 2014