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

Cystic Fibrosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00981214
• Other study ID #: EUR-1009-M
• Status: Completed
• Phase: Phase 3
• First received: September 21, 2009
• Last updated: February 24, 2014
• Start date: May 2006
• Est. completion date: September 2006

Study information

• Verified date: February 2014
• Source: Forest Laboratories
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: September 2006
• Est. primary completion date: September 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 7 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Cystic Fibrosis
• Exocrine Pancreatic Insufficiency
• Fibrosis

Intervention

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).

Locations

Country	Name	City	State
United States	University of Michigan, Cystic Fibrosis Center	Ann Arbor	Michigan
United States	University of Alabama	Birmingham	Alabama
United States	Childrens Memorial Hospital	Chicago	Illinois
United States	Children's Hospital Medical Center	Cincinnati	Ohio
United States	University of Florida College of Medicine	Gainsville	Florida
United States	University of Iowa	Iowa City	Iowa
United States	Nemours Childrens Clinic	Jacksonville	Florida
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	West Virginia Health Sciences Center	Morgantown	West Virginia
United States	Children's Hospital - Oakland	Oakland	California
United States	Stanford University Medical Center	Palo Alto	California
United States	University of Utah	Salt Lake City	Utah
United States	Children's Hospital of San Diego	San Diego	California
United States	University of Texas	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Forest Laboratories

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Who Were Responders After 1 Week of Treatment With Study Medication	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.	Day 11	No
Primary	Percentage of Participants Who Were Responders After 2 Weeks of Treatment With Study Medication	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.	Day 18 (end of treatment)	No
Secondary	Change From Baseline in Weight at Day 12, 19		Baseline, Day 12, 19	No
Secondary	Mean Daily Number of Stools	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.	Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)	No
Secondary	Percentage of Stool Categorized by Consistency	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.	Baseline, Day 5 up to Day 11 (dose stabilization period) and Day 12 up to Day 18 (treatment period)	No
Secondary	Mean Number of Abdominal Symptoms: Bloating	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.	Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)	No
Secondary	Mean Number of Abdominal Symptoms: Flatulence	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.	Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)	No
Secondary	Mean Number of Pain Symptoms	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.	Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)	No
Secondary	Physician's and Parent's or Legal Guardians Assessment of Improvement in Clinical Symptoms	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.	Day 19 (end of study)	No
Secondary	Percentage of Blood in Stool	Mean percentage of stools with blood at each period for total participants was summarized.	Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)	No
Secondary	Percentage of Stool With Visible Oil or Grease	Mean percentage of oil or grease at each period for total participants was summarized.	Baseline, Day 5 up to Day 11 (dose stabilization period), Day 12 up to Day 18 (treatment period)	No