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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Cystic Fibrosis, Exocrine Pancreatic Insufficiency

Intervention / Treatment
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* Drug: EUR-1008 (APT-1008)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Maximum Age: 7 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EUR-1008 (APT-1008)<br> | Drug: EUR-1008 (APT-1008)<br>* 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).<br>* Other names: Pancrelipase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Weight at Day 12, 19 |  | Baseline, Day 12, 19 | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 
| 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Zenpep-1009, Cystic fibrosis, Exocrine Pancreatic Insufficiency