A Study of the Enzyme Activity and Safety of Pancrelipase in Patients With Severe Exocrine Pancreatic Insufficiency (EPI)
Condition: Exocrine Pancreatic Insufficiency; Pancreatitis, Chronic; Steatorrhea; Pancreatitis
MeSH terms: Pancreatitis; Exocrine Pancreatic Insufficiency; Pancreatitis, Chronic; Steatorrhea
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of the study is to evaluate the enzyme activity and safety of pancrelipase in
      patients with severe Exocrine Pancreatic Insufficiency (EPI)
    

Detailed description: 
      Pancrelipase, the active ingredient in pancrelipase microtablet (MT) 21 capsules, is a
      pancreatic enzyme preparation (PEP) for oral administration that aids in the digestion of
      fats, sugars and proteins. Approximately 20 men and women from 18 to 85 years of age will be
      enrolled in the study. Patients enrolled must have severe pancreatic insufficiency with
      steatorrhea (presence of fat in the stool as a result of insufficient fat absorption in the
      digestive track) due to severe exocrine pancreatic insufficiency (EPI), a condition when the
      body is unable to digest food because the body does not have digestive enzymes made by the
      pancreas to digest fats, sugars and proteins properly for normal nutritional needs. The study
      will last approximately 25 days and will consist of a screening phase that will take place
      within 21 days before an open-label (patient knows the identity of the treatment they are
      receiving) treatment phase that will consist of 2 treatment periods (each treatment period
      will be approximately 4 hours long), a 2-day washout period between treatment periods, and an
      end-of-study evaluation upon successful completion of the sample collection in treatment
      period 2. Study participants will arrive at the study center no later than 6 p.m. on the day
      before treatment period 1 and stay overnight at the study center until the end-of-study
      evaluation in treatment period 2 (approximately 5 days). During the study, patients may not
      consume food or beverages containing alcohol, must refrain from the use of any
      methylxanthine-containing products, (eg, chocolate bars or beverages, coffee, teas, or
      colas), must eat only the meals provided during the study while residing at the study center,
      and must refrain from jogging, strenuous exercise of all types, and sunbathing. At the
      screening visit, patients will be asked to sign an informed consent form indicating that they
      understand the purpose of and procedures required for the study and are willing to
      participate in the study. Patients will then be asked to provide information regarding their
      medical history and will have a complete physical examination (including heart and
      respiration rate, blood pressure, temperature, height, and weight) performed. In addition, a
      blood sample (10 mL or approximately 2 teaspoons of blood) and a urine sample will be
      collected to assess the patient's general health. A urine pregnancy test will also be
      performed on women of childbearing age. If the patient is eligible to participate in the
      study, he/she will be asked to stop taking any existing pancreatic enzymes, prescription and
      nonprescription medications (including vitamins and herbal supplements) that could affect the
      stomach or intestines for 3 to 7 days before returning to the study center for treatment
      periods 1 and 2. During the study, patients will receive either Treatment A in Period 1 and
      Treatment B in Period 2; or Treatment B in Period 1 and Treatment A in Period 2. The day
      before (Day -1) of treatment period 1, patients will be randomly (by chance) assigned to 1 of
      2 treatment sequences (Treatment A or Treatment B). Treatment A will consist only of a
      high-fat liquid meal (500 mL of Ensure Plus containing 22.9 g of fat). Treatment B will
      consist of 3 PANCREASE MT 21 capsules taken orally (by mouth) along with a high-fat liquid
      meal (500 mL of Ensure Plus containing 22.9 g of fat). Following an overnight fast (without
      eating) of at least 10 hours, patients will be intubated (ie, have a tube inserted through
      their nose into the small intestine [duodenum]) in order to collect samples of fluid from
      their stomach and intestine before and after treatment in treatment periods 1 and 2. In
      treatment period 1, patients will be given the study treatment (Treatment A or Treatment B)
      orally (by mouth) over a 20-25 minute period, followed by a 2-hour sample collection period.
      After the sample completion period, the intubation tube will be removed and patients will
      have a washout period of at least 48 hours where they will rest and not receive treatment. At
      the end of the washout period, patients will enter treatment period 2 and receive the second
      study treatment. Patient's may be required to stay overnight for observation after the
      completion of the sample collection in Period 2, otherwise, patients will be permitted to
      leave the study center on Day 1 of treatment period 2 following a physical examination and
      collection of blood and urine samples for safety assessments. The primary outcome in the
      study is to evaluate the pharmacokinetics (enzyme activity) of intraduodenal enzyme (lipase,
      amylase, and protease) delivery of a single dose of 3 pancrelipase MT 21 capsules in gastric
      and duodenal fluid samples collected from patients before treatment and at 15 minute
      intervals up to 2 hours after treatment on Day 1 during each treatment period. During the
      study, the safety and tolerability of study drug will be monitored from the time of screening
      (Day -21) through to the end of the study procedures performed on Day 1 of treatment period 2
      by evaluating adverse events (side effects), results from clinical laboratory tests (serum
      chemistry, hematology, and urinalysis), vital signs (blood pressure, pulse, respiratory rate,
      and body temperature) measurements, and findings from physical examinations reported. Adverse
      events reported by patients were also monitored for up to 30 days following discharge from
      the study center. On Day 1 of the first treatment period, patients will receive Treatment A
      (a high-fat liquid meal of 500 ml of Ensure Plus) OR Treatment B (3 pancrelipase microtablet
      (MT) 21 capsules taken orally by mouth in addition to a high-fat liquid meal of 500 ml of
      Ensure Plus) ingested within 20-25 minutes. After a 2-day washout period, in the second
      treatment period, patients who received Treatment A in period 1 will receive Treatment B and
      patients who received Treatment B will receive Treatment A.
    

Intervention name(s): Ensure Plus; Pancrelipase in combination with Ensure Plus
Intervention type(s): Dietary Supplement; Drug
Intervention description(s): A high-fat liquid meal of 500 ml of Ensure Plus; 3 pancrelipase MT 21 capsules containing a total of 63,000 USP units of lipase with a high-fat liquid meal of 500 ml of Ensure Plus.
Intervention MeSH terms: Vitamin K; Pancrelipase; Pancreatin
Intervention model: Crossover Assignment
Keywords: Pancrelipase; PANCREASE MT; Cross-Over Studies; Duodenum; Intestine, Small; Lipase; Amylases; Peptide Hydrolases; Intubation; Safety; Capsules