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

Cystic Fibrosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00880100
• Other study ID #: UMT12CF08-01
• Status: Completed
• Phase: Phase 3
• First received: April 9, 2009
• Last updated: February 17, 2015
• Start date: April 2009
• Est. completion date: November 2009

Study information

• Verified date: February 2015
• Source: Forest Laboratories
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 6 Years

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cystic Fibrosis
• Exocrine Pancreatic Insufficiency
• Fibrosis
• Pancreatic Insufficiency

Intervention

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.

Locations

Country	Name	City	State
United States	University of Michigan Health System Cystic Fibrosis Center	Ann Arbor	Michigan
United States	The Children's Hospital	Aurora	Colorado
United States	Rainbow Babies and Children's Hospital - Cystic Fibrosis Center	Cleveland	Ohio
United States	Children's Medical Center of Dayton	Dayton	Ohio
United States	Duke University Medical Center	Durham	North Carolina
United States	Helen DeVos Children's Hospital-Spectrum Health Research Department	Grand Rapids	Michigan
United States	Pennsylvania State University and the Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	UW Hospital and Clinics	Madison	Wisconsin
United States	Respiratory Diseases of Children and Adolescents	Oklahoma City	Oklahoma
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	Virginia Commonwealth University	Richmond	Virginia
United States	University of Utah	Salt Lake City	Utah
United States	Sanford Children's Specialty Clinic	Sioux Falls	South Dakota
United States	SUNY Upstate Medical University	Syracuse	New York

Sponsors (1)

Lead Sponsor	Collaborator
Forest Laboratories

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)	No
Other	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)	No
Primary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No