A Study to Compare US Marketed Creon Manufactured With a Modernized Process at an Alternate Manufacturing Site and Manufactured With the Approved Manufacturing Process at an Alternate Active Pharmaceutical Ingredient Site, in Participants With Exocrine Pancreatic Insufficiency Due to Cystic Fibrosis

Cystic Fibrosis Clinical Trial

Official title:

A Phase 4 Study to Compare US Marketed Creon Drug Product With Drug Product Manufactured With a Modernized Process at an Alternate Manufacturing Site and With Drug Product Manufactured With the Approved Manufacturing Process at an Alternate Active Pharmaceutical Ingredient Site, in Subjects With EPI Due to Cystic Fibrosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03924947
• Other study ID #: M16-111
• Secondary ID: 2017-000578-12
• Status: Completed
• Phase: Phase 4
• Start date: October 23, 2019
• Est. completion date: July 11, 2022

Study information

• Verified date: September 2023
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Part 1 is a study to demonstrate that Creon (pancrelipase) delayed release (DR) capsules manufactured with a modernized process (MP) is non-inferior to currently marketed pancrelipase DR capsules in participants with exocrine pancreatic insufficiency (EPI) due to cystic fibrosis (CF), as measured by coefficient of fat absorption (CFA). Part 2 is a study to demonstrate that Creon (pancrelipase) manufactured with an alternate active pharmaceutical ingredient site (AAPIS) is non-inferior to currently marketed active control (Creon®) in participants with EPI due to CF, as measured by CFA. Safety is evaluated in each part.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: July 11, 2022
• Est. primary completion date: July 11, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

Inclusion Criteria:

• Participant has a documented diagnosis of Cystic Fibrosis (CF) confirmed by:

• a sweat chloride test >= 60 mmol/L, and/or

• documented CF-causing cystic fibrosis transmembrane conductance regulator (CFTR) mutations and clinical features of CF.

• Participant has diagnosis of moderate to severe Exocrine Pancreatic Insufficiency (EPI), as determined by Fecal Elastase 1 (FE-1) < 15 µg/g at screening.

• Participant has EPI that is currently clinically controlled (no clinically overt steatorrhea or diarrhea) under treatment with a commercially available Pancreatic Enzyme Replacement Therapy (PERT), on an individually established dose regimen for more than 3 months prior to Screening, with a daily dose not exceeding 4,000 Lipase Units (LU)/g fat/day or 10,000 LU/kg/day.

• Participant is available for two (if participating in one of the parts) or four (if participating in both parts) hospitalization/confinement periods of 6 to 8 days each during the expected study window.

• Participant is able to consume a diet with 100 g fat/day, a minimum of 1 g/kg of protein/day and normal to low fiber content.

Exclusion Criteria:

• BMI percentile for age less than 10% in participants less than 18 years of age.

• Participant has a history of any of the following gastrointestinal disorders (acute pancreatitis within 6 months prior to Visit 2, chronic pancreatitis, fibrosing colonopathy, distal intestinal obstruction syndrome (DIOS) within 6 months prior to Visit 2, C. difficile infection within 6 months prior to Visit 2, celiac disease, gastric bypass or partial/total gastrectomy, Crohn's disease or other inflammatory bowel disease, small bowel surgery (other than minor resection due to meconium ileus without resultant malabsorption syndrome), or any type of malignancy involving the digestive tract in the last 5 years).

• Participant has a history of any clinically significant endocrine, respiratory (except mild asthma or CF related lung disease), neurological, cardiac, renal, hepatic (including Hepatitis B or C), hematologic or psychiatric disease or disorder, or any other uncontrolled medical illness which might limit participation in or completion of the study.

• Participant requires concomitant treatment with any medication not allowed by the protocol or a prohibited medication is expected to be needed during the study.

• Participant is currently receiving nutritional supplementation via tube feeding (nasogastric, gastrostomy, jejunostomy).

• Participant has clinically significant (as per Investigator's judgment) abnormalities in clinical chemistry, hematology, or urinalysis (excluding findings that are associated with CF) such as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels >= 3 times the upper limit of normal values, or clinically significant (investigator opinion) elevation of uric acid.

Related Conditions & MeSH terms

• Cystic Fibrosis
• Exocrine Pancreatic Insufficiency
• Fibrosis

Intervention

Drug:
• Pancrelipase
Delayed release capsules
• Pancrelipase
Delayed release capsules

Locations

Country	Name	City	State
United States	Cleveland Clinic Main Campus /ID# 212853	Cleveland	Ohio
United States	UH Cleveland Medical Center /ID# 206095	Cleveland	Ohio
United States	Nationwide Children's Hospital /ID# 225628	Columbus	Ohio
United States	University of Iowa Hospitals and Clinics /ID# 164551	Iowa City	Iowa
United States	Nemours Children's Health System /ID# 164553	Jacksonville	Florida
United States	University of Southern California /ID# 164571	Los Angeles	California
United States	Vanderbilt University Medical Center /ID# 213434	Nashville	Tennessee
United States	The Cystic Fibrosis Institute /ID# 210757	Northfield	Illinois
United States	Central FL Pulmonary Orlando /ID# 164558	Orlando	Florida
United States	Children's Hospital of Philadelphia - Main /ID# 208114	Philadelphia	Pennsylvania
United States	Virginia Commonwealth University Medical Center Main Hospital /ID# 164574	Richmond	Virginia
United States	Landon Pediatric Foundation /ID# 215411	Ventura	California
United States	Via Christi Research /ID# 214266	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1 Coefficient of Fat Absorption (CFA)	CFA is calculated as 100*[fat intake - fat excretion]/fat intake. Fat intake was determined from fat content of food consumed on Day 3, 4, 5 of each treatment period. Fat excretion was determined from the content in the stool(s) collected after the first blue dyed stool (exclusive) following administration of the first blue dye marker (day 2) and until the first dyed stool (inclusive) following administration of the second blue dye marker (day 5) during each treatment period.	Up to Day 8 of each DB treatment period
Primary	Part 2 Coefficient of Fat Absorption (CFA)	CFA is calculated as 100*[fat intake - fat excretion]/fat intake. Fat intake was determined from fat content of food consumed on Day 3, 4, 5 of each treatment period. Fat excretion was determined from the content in the stool(s) collected after the first blue dyed stool (exclusive) following administration of the first blue dye marker (day 2) and until the first dyed stool (inclusive) following administration of the second blue dye marker (day 5) during each treatment period.	Up to Day 8 of each DB treatment period
Secondary	Coefficient of Nitrogen Absorption (CNA)	The CNA is calculated as 100*[nitrogen intake - nitrogen excretion]/nitrogen intake. Nitrogen intake was determined from protein content of food consumed on Day 3, 4, 5 of each treatment period. Nitrogen excretion was determined from the content in the stool(s) collected after the first blue dyed stool (exclusive) following administration of the first blue dye marker (day 2) and until the first dyed stool (inclusive) following administration of the second blue dye marker (day 5) during each treatment period.	Up to Day 8 of each DB treatment period
Secondary	Stool Fat	Total amount of fat excreted during the stool collection period. Stool fat was determined from the stool fat in the stool(s) collected after the first blue dyed stool (exclusive) following administration of the first blue dye marker (day 2) and until the first dyed stool (inclusive) following administration of the second blue dye marker (day 5) during each treatment period.	Up to Day 8 of each DB treatment period
Secondary	Stool Weight	Stool weight was determined from the net weight of the stool samples collected after the first blue dyed stool (exclusive) following administration of the first blue dye marker (day 2) and until the first dyed stool (inclusive) following administration of the second blue dye marker (day 5) during each treatment period.	Up to Day 8 of each DB treatment period

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