Study to Evaluate the Safety and Efficacy of EUR-1008 (APT-1008) Pancreatic Enzyme Product in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
Condition: Cystic Fibrosis; Exocrine Pancreatic Insufficiency
MeSH terms: Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Fibrosis
Intervention: EUR-1008 (APT-1008); Placebo; Placebo; EUR-1008 (APT-1008)
Intervention description: EUR-1008 (APT-1008) microtablets (5000 lipase units) or minitablets (10000, 15000 or 20000 lipase units) contained in a capsule will be given orally daily in first double-blind intervention period; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). The capsules could be opened and sprinkled on acidic food and half of the established dose was used with snacks. Treatment duration for first double-blind intervention period will be 2 days home treatment and 3 to 5 days hospital treatment.; Placebo matched to EUR-1008 (APT-1008) microtablets or minitablets contained in a capsule will be given orally daily in second double-blind intervention period; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). Treatment duration for second double-blind intervention period will be 2 days home treatment and 3 to 5 days hospital treatment.; Placebo matched to EUR-1008 (APT-1008) microtablets or minitablets contained in a capsule will be given orally daily in first double-blind intervention period; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). Treatment duration for first double-blind intervention period will be 2 days home treatment and 3 to 5 days hospital treatment.; EUR-1008 (APT-1008) microtablets (5000 lipase units) or minitablets (10000, 15000 or 20000 lipase units) contained in a capsule will be given orally daily in second double-blind intervention period; at a dose based on investigator's discretion as achieved during dose titration and stabilization period (6 to 9 days). Treatment duration for second double-blind intervention period will be 2 days home treatment and 3 to 5 days hospital treatment.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Enrollment: 34.0
Sex: All
Minimum age: 7 Years
Healthy volunteers: No
Keywords: CF; Cystic Fibrosis; EPI; Exocrine Pancreatic Insufficiency; Pancreatic; Enzyme; PEP

Summary:

      The primary efficacy objective of this study is to compare the coefficient of fat absorption
      (CFA) following oral administration of Aptalis Pharma's (formerly Eurand Pharmaceuticals)
      pancreatic enzyme product (PEP) capsules and placebo in participants with cystic fibrosis
      (CF) and exocrine pancreatic insufficiency (EPI).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants with age greater than or equal to (>=) 7 years at the time of enrollment

          -  Participants with weight 70 kg or less and be in an adequate nutritional status as
             indicated by a body mass index (BMI) >=20 kg/m^2 for ages 18 and above, or a BMI above
             the twenty fifth percentile for participants aged 7 to 17 years

          -  Participants with confirmed diagnosis of CF who 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 by
             quantitative pilocarpine iontophoresis

          -  Participants with confirmed diagnosis of EPI who are currently receiving treatment
             with a commercially available PEP and have documented with a fecal elastase of <100
             microgram per gram stool (if no documentation was available, a stool sample was taken
             at Screening for determination of fecal elastase).

          -  Clinically stable participants with no evidence of acute respiratory disease or any
             other acute condition

          -  Participants who are willing and able to interrupt current CF treatment for CF-related
             malabsorption along with any medications that may affect gastric motility or stomach
             power of hydrogen (pH)

          -  Participants 18 years of age and older had to a) understand the requirements of the
             study, b) provide written informed consent, c) agree to abide by the study
             restrictions, and d) return for the required assessments

          -  Participants 7 to 17 years of age must have a parent(s) or legal guardian who provides
             written informed consent, agree to abide by the study restrictions

          -  Females participants of childbearing potential must have a negative serum pregnancy
             test at screening and must agree to use adequate birth control during the study

        Exclusion Criteria:

          -  Participants with fibrosing colonopathy, hyperuricemia or hyperuricosuria

          -  Participants who are allergic to pork or other porcine PEPs

          -  Participants with forced expiratory volume (FEV1) <30 percent of predicted FEV1 at
             screening

          -  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 or chronic treatment
             with an inhalatory antibiotic is allowed

          -  Participants with hepatic insufficiency as defined by history or presence of ascites
             or serum albumin level of < 3.0 milligram/deciliter, or a coagulopathy with an
             international normalized ratio that is greater than 1.7

          -  Participants who have used an acute dose of any steroid in the previous 2 weeks;
             however, low chronic doses of a steroid is allowed

          -  Participants with history of or current diagnosis of distal ileal obstruction syndrome
             (DIOS) as evidenced or suggested by constipation, abdominal pain, anorexia, early
             satiety, recurrent vomiting, and palpable fecal mass on physical examination (the
             absence of DIOS will be confirmed by an X-ray of the abdomen taken at screening)

          -  Participants with any solid organ transplant or surgery affecting the bowel.
             Participants with a history of appendectomy and inguinal (non-incarcerated)
             hernioplasty or meconium ileus without the need for bowel resection could be enrolled.
             Gastrointestinal-tube-fed patients, in absence of dumping syndrome, were also eligible

          -  Participants with history of or current screening evaluation of hyperglycemia as
             defined by an 8-hour fasting blood glucose (FBG) of >126 mg/dL, or of CF-related
             diabetes as determined according to the Cystic Fibrosis Foundation (CFF) Consensus
             Conference of January 1999 (Section IX Part II), that is: a) FBG >126 mg/dL (7.0
             millimoles per liter [mmol/L]) on two or more occasions b)FBG >126 mg/dL (7.0 mmol/L)
             plus casual (without regard to time of day or last meal consumed) glucose level >200
             mg/dL (11.1 mmol/L) c)Casual (previously called random) glucose levels >200 mg/dL
             (11.1 mmol/L) on two or more occasions with symptoms

          -  Participants using an enzyme preparation in excess of 10,000-lipase units/kg/day

          -  Participants using an immunosuppressive drug

          -  Participants who are expecting an inability to tolerate the washout period and/or the
             placebo treatment

          -  Participants participating in an investigational study of a drug, biologic, or device
             not currently approved for marketing, within 30 days of screening visit

          -  Female participants who are pregnant or breastfeeding, or unwilling to use effective
             birth control during study

          -  Participants with any condition that would, in the investigator's opinion, limit the
             participant's ability to complete the study