Clinical Trial: Control of Steatorrhea in Participants With Cystic Fibrosis and Exocrine Pancreatic Insufficiency

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: An Open-label, Multicenter, Randomized, Cross-over Study to Compare the Safety and Efficacy of PANZYTRAT® 25,000 to KREON® 25,000 in the Control of Steatorrhea in Subjects Aged 7 Years and O

Brief Summary: This study by Aptalis (formerly Axcan) assesses the efficacy and safety of Panzytrat® 25,000 compared to Kreon® 25,000 in the control of steatorrhea in participants with cystic fibrosis (CF) and exocrine pancreatic insufficiency (EPI).

Detailed Summary:

This is an open-label, Phase IV, multicenter, randomized, two-period cross-over study to compare the efficacy and safety of Panzytrat® 25,000 to Kreon® 25,000 in participants aged 7 years and older suffering from CF and EPI. The study consists of a qualification phase (5 to 15 days); two treatment periods of 14 days each (plus a 3-day window if needed) and a 3-day stool collection will be performed from Days 12 to 15.

A safety follow-up phone call will be arranged 7-10 days after completion of the treatment phase or after an early discontinuation.


Sponsor: Forest Laboratories

Current Primary Outcome: Percent Coefficient of Fat Absorption (CFA) [ Time Frame: Day 12 up to Day 15 in first and second treatment periods ]

Percent CFA was calculated as ([fat intake - fat excretion]/fat intake)*100, determined in the stools which were collected over a 3-day period (Day 12 to morning of Day 15) during each treatment period. Least squares mean percent (%) CFA was calculated for Day 12 to Day 15 in first and second treatment periods. Percent CFA was based on log transformed data.


Original Primary Outcome: Coefficient of Fat Absorption [ Time Frame: During 72 hours after 14 days of treatment ]

Current Secondary Outcome:

  • Mean Daily Number of Stools [ Time Frame: Day 12 up to Day 15 in first and second treatment periods ]
    Mean daily number of stools of each participant was calculated from frequency of stools by the participant per day. Mean daily number of stools during the collection period (Day 12 to Day 15 in first and second treatment periods) for total participants was summarized.
  • Percentage of Stools With Normal Consistency [ Time Frame: Day 12 up to Day 15 in first and second treatment periods ]
    Normal consistency of stool was defined as formed hard, normal or soft stool and abnormal consistency was defined as loose and unformed, liquid stool and diarrhea. Percentage of stools with normal consistency of each participant was calculated as the number of stools with normal consistency relative to the total number of stools during the collection period. Mean percentage of stool with normal consistency during the collection period (Day 12 to Day 15 in first and second treatment periods) for total participants was summarized.
  • Total Weight of Stools [ Time Frame: Day 12 up to Day 15 in first and second treatment periods ]
    Mean total weight of stools was calculated for Day 12 to Day 15 in first and second treatment periods.
  • Mean Weight Per Stool Sample [ Time Frame: Day 12 up to Day 15 in first and second treatment periods ]
    Mean weight per stool sample was calculated for Day 12 to Day 15 in first and second treatment periods.
  • Relative Frequency of Days With Abdominal Symptoms [ Time Frame: Day 1 up to Day 15 in first and second treatment periods ]
    Abdominal symptoms included abdominal pain and flatulence. Symptoms were classified by severity as mild (no impairment of daily activities), moderate (slight impairment of daily activities), or severe (unable to perform daily activities). For each type of abdominal symptom, the relative frequency of days with the symptom for each participant in a treatment period was calculated as the number of days in which the symptom was reported divided by the total number of days in which the abdominal symptom case report form (CRF) was completed. Mean relative frequency of days with abdominal symptoms was calculated during each treatment period (Day 1 to Day 15).
  • Percentage of Participants With Abdominal Distension [ Time Frame: Day 1 up to Day 15 in first and second treatment periods ]
    Abdominal distension is a sense of increased abdominal pressure by the participant that involves an actual measurable change in the circumference of a participant's abdomen on physical examination. Percentage of participants with abdominal distension was calculated for each treatment period (Day 1 to Day 15).
  • Percent Coefficient of Fat Absorption (CFA) Based on Concomitant Use of Proton Pump Inhibitors (PPIs) [ Time Frame: Day 12 up to Day 15 in first and second treatment periods ]
    Percent CFA was calculated as ([fat intake - fat excretion]/fat intake)*100, determined in the stools which were collected over a 3-day period (Day 12 to morning of Day 15) during each treatment period. Least squares mean percent (%) CFA was calculated for Day 12 to Day 15 in first and second treatment periods. Percent CFA was based on log transformed data. Percent CFA was calculated separately for participants who used and did not use acid suppressing therapy (PPIs) during the study.
  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 30 days after last dose ]
    An AE was defined as any untoward medical occurrence regardless of its causal relationship to study drug. A TEAE was defined as any event not present prior to exposure to study drug or any event already present that worsens in either intensity or frequency following exposure to test drug. A SAE was defined as any event that results in death, is immediately life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect or is assessed as medically important.
  • Nutritional Status as Assessed by Body Weight [ Time Frame: Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation ]
    Mean body weight was calculated at end of treatment (within 3 days after Day 15 of first and second treatment periods).
  • Nutritional Status as Assessed by Body Mass Index (BMI) [ Time Frame: Baseline, end of treatment (within 3 days after Day 15 of first and second treatment periods) or early discontinuation ]
    Nutritional status of participants was assessed by determining their BMI. BMI was calculated by dividing body weight (kg) by square of height in meter (m). Mean BMI was calculated at end of treatment (within 3 days after Day 15 of first and second treatment periods).
  • Nutritional Status as Assessed by Electrolytes Level [&nb

    Original Secondary Outcome:

    • Stool frequency [ Time Frame: 2 periods of 3 days each ]
    • Stool consistency [ Time Frame: 2 periods of 3 days each ]
    • Stool weight [ Time Frame: 2 periods of 3 days each ]
      Total stool weight and mean weight per stool sample will be assessed
    • Frequency of subject's abdominal symptoms [ Time Frame: During both study treatments (28 to 34 days) ]
      Abdominal pain and excessive flatulence/gas production will be assessed as abdominal symptoms.
    • Presence of abdominal distension [ Time Frame: Visits 1, 3 and 4 ]
    • Role of acid suppression therapy on Coefficient of Fat Absorption [ Time Frame: 2 periods of 3 days each ]
      Each subject will be categorized as an ''acid suppression therapy user'' or a ''non-user''. For both sub-categories (use and no use of acid suppresion therapy), the CFA% measured with the two study drugs will be assessed to see if the use of acid suppresion therapy tends to affect or not the CFA%.
    • Nutritional status of subjects [ Time Frame: Visits 1, 3 and 4 ]
      The nutritional status of subjects will be briefly described at Visit 1 (baseline) with parameters such as body weight and BMI, as well as blood levels of hemoglobin, hematocrit, transferrin, albumin, electrolytes, vitamins A, D and E. Except for vitamins A, D and E, the other blood level parameters will be compared to baseline at Visit 4 and weight and BMI will be compared to baseline at Visits 3 and 4.
    • Number of adverse events reported by the subjects or found during physical examination or blood and urine tests [ Time Frame: From signature of ICF (Visit 1) to completion of the study (scheduled 7-10 days after Visit 4) or until discontinuation of the study ]
    • Severity of subject's abdominal symptoms [ Time Frame: During both study treatments (28 to 34 days) ]
      The severity of abdominal symptoms reported by the subject, respectively abdominal pain and excessive flatulence/gas production will be assessed.
    • Nature of adverse events reported by the subjects or found during physical examination or blood and urine tests [ Time Frame: From signature of ICF (Visit 1) to completion of the study (scheduled 7-10 days after Visit 4) or until discontinuation of the study ]


    Information By: Forest Laboratories

    Dates:
    Date Received: March 28, 2011
    Date Started: April 2011
    Date Completion:
    Last Updated: March 5, 2014
    Last Verified: March 2014