Use of Ultrase® MT12 in Young Cystic Fibrosis Children (CF)

Efficacy and Safety of Ultrase MT12 in the Control of Steatorrhea in Cystic Fibrosis (CF) and Pancreatic Insufficient (PI) Children Aged 2 to 6 Years Old

Multicenter, explorative, phase IIIb, open-label study to assess the efficacy and safety of Ultrase® MT12, in the control of steatorrhea and clinical signs and symptoms of malabsorption in CF children with pancreatic insufficiency (PI). This study is sponsored by Aptalis Pharma (formerly Axcan).

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis; Pancreatic Insufficiency
• Intervention / Treatment: Drug: Ultrase® MT12

Detailed Description

This is a multicenter, explorative, phase IIIb, open-label study in patients with CF and PI. The study consists of a screening visit (visit 1), followed by a baseline phase of 9 days (plus a 5-day window if necessary) during which the regular pancreatic enzyme will be maintained and 10 stool samples will be collected over 5 days, for baseline evaluation of steatorrhea. Afterward, a treatment phase of 19 days (plus a 5-day window if necessary) with Ultrase® MT12 will follow (the usual pancreatic enzyme will be replaced by Ultrase® MT12). Over the last 5 days of the treatment phase, 10 additional stool samples will be collected, for evaluation of steatorrhea.

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • The Children's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-0212
      • University of Michigan Health System Cystic Fibrosis Center
    • Grand Rapids, Michigan, United States, 40503
      • Helen DeVos Children's Hospital-Spectrum Health Research Department
  • New York
    • Syracuse, New York, United States, 13203
      • SUNY Upstate Medical University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Rainbow Babies and Children's Hospital - Cystic Fibrosis Center
    • Dayton, Ohio, United States, 45404
      • Children's Medical Center of Dayton
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Oklahoma City, Oklahoma, United States, 73112
      • Respiratory Diseases of Children and Adolescents
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Pennsylvania State University and the Milton S. Hershey Medical Center
    • Pittsburgh, Pennsylvania, United States, 15213
      • Children's Hospital of Pittsburgh of UPMC
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117-5039
      • Sanford Children's Specialty Clinic
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • UW Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 6 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients aged 2 to 6 years inclusively
• Patients with current diagnosis of CF based on one or more typical clinical features of CF or a sibling with CF or a positive newborn screening and at least either with sweat chloride test greater than or equal to 60 millimoles/liter (mmol/L) by quantitative pilocarpine iontophoresis on two separate occasions or two identifiable CF-causing mutations
• Patients with presence of PI as demonstrated by fecal elastase (FE-1) less than 100 microgram/gram (mcg/g) of stools (performed by ScheBo test) and requiring pancreatic enzyme supplementation
• Patients who are able to eat a high-fat diet calculated at a value between 2g to 4g fat/kg of body weight per day during the whole study and having a current adequate nutritional status based on the body mass index (BMI) greater than or equal to fifth percentile
• Patients receiving current treatment of PI with pancreatic enzymes
• The parent or legal guardian signed informed consent form (ICF) and is mentally able to understand and comply with the study procedures

Exclusion Criteria:

• Patients currently receiving or received an Ultrase® MT product (MT12, MT18, MT20) for PI in the last 30 days
• Patients having known contraindication, sensitivity or hypersensitivity to Ultrase® or to any porcine protein
• Patients with presence of a medical condition known to increase fecal fat loss or that could compromise study results or the study patient safety
• Patients with current diagnosis or history of complete distal intestinal obstruction syndrome (DIOS) in the past 6 months or who had 2 or more episodes of incomplete DIOS in the past year
• Patients with use of any prohibited medication or product at study entry and during the course of the study
• Patients with chronic use of narcotics
• Patients with use of bowel stimulants and/or laxatives more than once a week
• Patients with presence of acute pancreatitis or exacerbation of chronic pancreatic disease
• Patients with presence of an acute infection that needed to be treated with oral or intravenous (IV) broad-spectrum antibiotics
• Patients having history of significant bowel resection; small bowel resection for meconium ileus at birth and appendectomy were accepted. Patients with Presence of dysmotility disorders
• Patients with presence of chronic or severe abdominal pain
• Patients unable to comply with diet requirement
• Patients receiving enteral tube feeding overnight at study entry or who will need to receive enteral tube feeding overnight during the course of the study
• Patients with history of or a current diagnosis of clinically significant portal hypertension
• Patients with presence of poorly controlled diabetes according to the Investigator's clinical judgment
• Patients having any condition or pre-study laboratory abnormality or history of any illness which, in the opinion of the Investigator, might have put the patient at risk, prevented the patient from completing the study, or otherwise affect the outcome of the study
• Patient with use of any investigational drug within 30 days prior to the date of signature of the ICF

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ultrase® MT12	Drug: Ultrase® MT12; Ultrase® MT12 capsules will be given orally daily based on investigator's discretion to a maximum dose of 2,500 lipase units per kilogram (kg) body weight per meal or snack for 19 to 24 days during the treatment phase. Total maximum dose not to exceed 10,000 lipase units/kg/day.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With Control of Steatorrhea	Control of steatorrhea was defined as a less than 30 percent (%) of fat in stools as measured by nuclear magnetic resonance (NMR) spectroscopy in all stool samples which are collected at baseline phase (usual pancreatic enzymes) during which the patients were on their prescribed pancreatic enzyme product (PEP) and during the 5-day collection period of the treatment phase during which the PEP was replaced with Ultrase MT12.	A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Patients With Normal Stool Frequency	Normal stool frequency was defined as having less than 4 bowel movements per day in baseline phase (usual pancreatic enzymes) during which the patients were on their prescribed pancreatic enzyme product (PEP) and 5-day collection period of the Treatment Phase during which the PEP was replaced with Ultrase MT12.	A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)
Percentage of Stools With Normal Consistency	Normal consistency of stool was defined as hard and formed or soft and formed consistency. Abnormal consistency was defined as loose and unformed stool or liquid stools and diarrhea. Percentage of stools with normal consistency of each patient was calculated from normal consistency of stools by the patient per day. Mean percentage of stools with normal consistency in baseline phase (usual pancreatic enzymes) during which the patients were on their prescribed pancreatic enzyme product (PEP) and 5-day collection period of the treatment phase during which the PEP was replaced with Ultrase MT12, for total patients was summarized.	A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)
Percentage of Stools With Abnormal Characteristics	Stools of abnormal characteristics were defined as bulky/large, foul-smelling and/or oily stools. Mean percentage of stools with abnormal characteristics in baseline phase (usual pancreatic enzymes) during which the patients were on their prescribed pancreatic enzyme product (PEP) and 5-day collection period of the treatment phase during which the PEP was replaced with Ultrase MT12, for total patients was summarized.	A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)
Mean Number of Days Without Abdominal Complaints	Abdominal complaints were defined as the reporting of abdominal pain and/or unusual and excessive flatulence/gas production. Mean number of days without abdominal complaints in baseline phase (usual pancreatic enzymes) during which the patients were on their prescribed pancreatic enzyme product (PEP) and 5-day collection period of the treatment phase during which the PEP was replaced with Ultrase MT12, for total patients was summarized.	A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Weight of Stools	The total weight of stools in grams (g) is the total weight obtained during the stool collection period regardless of the number of stools that had been collected during this same collection period. Mean total weight of stools in baseline phase (usual pancreatic enzymes) during which the patients were on their prescribed pancreatic enzyme product (PEP) and 5-day collection period of the treatment phase during which the PEP was replaced with Ultrase MT12, for total patients was summarized.	A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)
Percentage of Days With Abdominal Pain and Excessive Flatulence	Mean percentage of days with abdominal complaints during baseline phase (BP) and the 5-day collection period of the treatment phase for total patients was summarized. Abdominal complaints were defined as the reporting of abdominal pain and/or unusual and excessive flatulence/gas production. Mean number of days abdominal pain (AP) and excessive flatulence (EF) in baseline phase (usual pancreatic enzymes) during which the patients were on their prescribed pancreatic enzyme product (PEP) and 5-day collection period of the treatment phase during which the PEP was replaced with Ultrase MT12, for total patients was summarized.	A period of 19 to 24 days, from Baseline (Visit 2) to Day 15 to19 of Treatment Phase (Visit 3)

Collaborators and Investigators

• Sponsor: Forest Laboratories

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (Actual): November 1, 2009
• Study Completion (Actual): November 1, 2009

Study Registration Dates

• First Submitted: April 9, 2009
• First Submitted That Met QC Criteria: April 9, 2009
• First Posted (Estimate): April 13, 2009

Study Record Updates

• Last Update Posted (Actual): March 16, 2017
• Last Update Submitted That Met QC Criteria: February 8, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Abdominal pain; Steatorrhea; Malabsorption of fat; Pancreatic enzymes; Greasy stools
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Pancreatic Diseases; Fibrosis; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Gastrointestinal Agents; Pancrelipase; Pancreatin
• Other Study ID Numbers: UMT12CF08-01