A Study of the Efficacy and Tolerability of Pancrelipase Microtablet (MT) Capsules for the Treatment of Cystic Fibrosis-dependent Exocrine Pancreatic Insufficiency
Condition: Exocrine Pancreatic Insufficiency; Steatorrhea; Malabsorption Syndromes; Cystic Fibrosis
MeSH terms: Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Malabsorption Syndromes; Steatorrhea; Fibrosis
Study type: Interventional
Phase: Phase 3

Summary: 
      The purpose of this study is to assess the effectiveness and safety of oral pancrelipase MT
      in the treatment of adult and pediatric/adolescent cystic fibrosis (CF) patients with
      clinical symptoms of exocrine pancreatic insufficiency (EPI).
    

Detailed description: 
      This is a randomized, placebo-controlled, double-blind withdrawal, multicenter study to
      evaluate the effectiveness of pancrelipase MT capsules compared with placebo in the treatment
      of adult (>18 to 60 years of age) and children/adolescent (7 to <18 years of age) patients
      with CF and who require pancreatic enzyme replacement therapy (PERT) to control clinical
      symptoms of EPI and steatorrhea (excess fat in the feces). The study has 3 phases: a
      screening phase, an open-label (run-in) phase, and a double-blind withdrawl phase. The study
      including the screening phase will be approximately 28 days in length. In the screening
      phase, patients will begin a high-fat diet and will take pancrelipase MT10.5 or MT21 capsules
      (or a combination of both) orally with meals (or snacks) to optimize digestion based on
      clinical signs and symptoms. In the open-label phase patients will continue taking their
      optimal dose of study drug. After a minimum of 3 days in the open-label treatment phase, an
      inpatient 72-hour stool collection period for fecal fat determination will be performed.
      Patients with a coefficient of fat absorption (COA)-fat of 80% or greater who have completed
      at least 6 days on a controlled high-fat diet will be eligible for the double-blind
      withdrawal phase of the study and will be randomly assigned to receive placebo or
      pancrelipase MT. After a minimum of 1 day on double-blind treatment and with the presence of
      deteriorating clinical signs and symptoms, patients will be admitted to the clinic to begin a
      second 72-hour inpatient stool collection period. Effectiveness evaluations will be performed
      throughout the study and consist of stool collection for determination of COA-fat and
      coefficient of protein absorption (COA-protein), stool diary, nutrition worksheet, and
      Clinical Global Impression-Severity of illness (CGI-S), Clinical Global Impression-Change
      (CGI-C), and Global Assessment of Change (GAC) scales. Signs and symptoms exhibited during
      the study will be monitored and will include the presence or absence of diarrhea, abdominal
      pain, nausea, vomiting, bloating, and a description of stool changes. Safety will be
      montitored during the study by evaluating adverse events and findings from clinical
      laboratory tests, vital signs measurements, and physical examinations. The study hypothesis
      is that the study drug will be more effective than placebo as measured by the change in the
      coefficient of fat absorption (COA-fat) in adults and pediatric/adolescent patients with EPI
      secondary to CF. Pancrelipase MT10.5 or MT21 capsules (or a combination of both) will be
      taken orally with meals (or snacks) within the recommended ranges of pancreatic enzyme
      therapy as recommended by the CF Foundation and up to a maximum 10,000 lipase units per
      kilogram [kg] per day. All patients will take pancrelipase MT for 6 days in the screening
      phase and for approximately 6 to 10 days in the open-label phase; patients will take
      pancrelipase MT or placebo for 4 to 7 days in the double-blind phase.
    

Intervention name(s): Pancrease MT 10.5, or MT 21; Placebo for Pancrease MT 10.5 or MT 21
Intervention type(s): Drug; Drug
Intervention description(s): Pancrease MT capsules for maximum dose of 10,000 lipase units / Kg / day; Capsules with Pancrease MT excipients without the active enzymes
Intervention MeSH terms: Pancrelipase; Pancreatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Exocrine pancreatic insufficiency; Steatorrhea; Malabsorption syndromes; Cystic fibrosis; Pediatrics; Adult; Pancrelipase