Clinical trial NCT00297167: Study to Evaluate the Safety and Efficacy of EUR-1008 (APT-1008) Pancreatic Enzyme Product in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
Official title: A Randomized, Double-Blind, Placebo-Controlled, Two-Treatment, Crossover Study to Evaluate the Safety and Efficacy of Eurand Pancreatic Enzyme Product (PEP) in Patients With Cystic Fibrosis and Exocrine Pancreatic Insufficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cystic Fibrosis
Exocrine Pancreatic Insufficiency
Keywords: CF
Cystic Fibrosis
EPI
Exocrine Pancreatic Insufficiency
Pancreatic
Enzyme
PEP
Lead sponsor: Forest Laboratories
Sponsor class: INDUSTRY
First posted: 2006-02-28
Enrollment: 34
Sex: ALL
Minimum age (years): 7
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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).

Detailed description: This is a randomized, double-blind, placebo-controlled, 2-treatment, crossover, multicenter trial in participants with CF and EPI. The study consists of a screening period (1 to 14 days), a washout period (2 days), a dose titration/stabilization period (6 to 9 days), a blinded randomized treatment period (6 to 7 days), an open-label normalization period 1 (5 to 14 days), a blinded crossover treatment period (6 to 7 days), followed by an open-label normalization period 2 (7 days). The order of treatments (placebo followed by EUR-1008 \[APT-1008\] or EUR-1008 \[APT-1008\] followed by placebo) will be determined by randomization at the beginning of randomization treatment period only and will be carried through the crossover treatment period. The starting dose will be 1,000 lipase units per kilogram per meal (lipase units/kg/meal), which will be titrated to control symptoms of EPI, with the total dose not exceeding 10,000 lipase units/kg/day.

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

Primary outcomes:
measure: Percent Coefficient of Fat Absorption (CFA%)
timeFrame: Day 3 up to Day 6 of hospital treatment in first and second double-blind intervention periods
Secondary outcomes:
measure: Percent Coefficient of Nitrogen Absorption (CNA%)
timeFrame: Day 3 up to Day 6 of hospital treatment in first and second double-blind intervention periods
measure: Lipid Levels
timeFrame: End of treatment (Day 6 during first and second double-blind intervention periods)
measure: Vitamin A Levels
timeFrame: End of treatment (Day 6 during first and second double-blind intervention periods)
measure: Vitamin E Levels
timeFrame: End of treatment (Day 6 during first and second double-blind intervention periods)
measure: Mean Daily Number of Stools
timeFrame: Day 3 up to Day 6 during first and second double-blind intervention periods
measure: Percentage of Stool Categorized as Per Consistency
timeFrame: Day 3 up to Day 6 during first and second double-blind intervention periods
measure: Mean Number of Abdominal Symptoms
timeFrame: Day 3 up to Day 6 during first and second double-blind intervention periods
Other outcomes:
measure: Percentage of Visible Oil or Grease in Stool
timeFrame: Day 3 up to Day 6 of hospital treatment in first and second double-blind intervention periods
measure: Percentage of Stools With Blood
timeFrame: Day 3 up to Day 6 of hospital treatment in first and second double-blind intervention periods
Locations:
city: Tyler
country: United States
facility: University of Texas Health Center at Tyler
state: Texas
Study officials:
affiliation: Forest Laboratories
name: Aptalis Medical Information
role: STUDY_DIRECTOR
References:
citation: Wooldridge JL, Heubi JE, Amaro-Galvez R, Boas SR, Blake KV, Nasr SZ, Chatfield B, McColley SA, Woo MS, Hardy KA, Kravitz RM, Straforini C, Anelli M, Lee C. EUR-1008 pancreatic enzyme replacement is safe and effective in patients with cystic fibrosis and pancreatic insufficiency. J Cyst Fibros. 2009 Dec;8(6):405-17. doi: 10.1016/j.jcf.2009.07.006. Epub 2009 Aug 15.