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

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

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.

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis
• Intervention / Treatment: Drug: Pancrelipase

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • University of Southern California /ID# 164571
    • Ventura, California, United States, 93003-3099
      • Landon Pediatric Foundation /ID# 215411
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Health System /ID# 164553
    • Orlando, Florida, United States, 32803
      • Central FL Pulmonary Orlando /ID# 164558
  • Illinois
    • Northfield, Illinois, United States, 60093
      • The Cystic Fibrosis Institute /ID# 210757
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics /ID# 164551
  • Kansas
    • Wichita, Kansas, United States, 67214-2878
      • Via Christi Research /ID# 214266
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • UH Cleveland Medical Center /ID# 206095
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Main Campus /ID# 212853
    • Columbus, Ohio, United States, 43205-2664
      • Nationwide Children's Hospital /ID# 225628
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-4319
      • Children's Hospital of Philadelphia - Main /ID# 208114
  • Tennessee
    • Nashville, Tennessee, United States, 37232-0011
      • Vanderbilt University Medical Center /ID# 213434
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth University Medical Center Main Hospital /ID# 164574

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 Double-Blind Creon MP / Creon; After receiving open-label currently marketed Creon delayed release (Creon DR) capsules during a pre-randomization period, participants receive double-blind Creon DR capsules manufactured by modernized process pellets (Creon MP) in treatment period 1, followed by double-blind Creon DR capsules in treatment period 2. Participants also receive open-label currently marketed Creon DR for an interval of up to 28 days between periods 1 and 2, and during a 30-day follow-up period after period 2.	Drug: Pancrelipase; Delayed release capsules; Other Names: Creon; ABT-SLV-245; Creon AAPIS
Experimental: Part 1 Double-Blind Creon / Creon MP; After receiving open-label currently marketed Creon DR capsules during a pre-randomization period, participants receive double-blind Creon DR capsules in treatment period 1, followed by double-blind Creon MP in treatment period 2. Participants also receive open-label currently marketed Creon DR for an interval of up to 28 days between periods 1 and 2, and during a 30-day follow-up period after period 2.	Drug: Pancrelipase; Delayed release capsules; Other Names: Creon; ABT-SLV-245; Creon AAPIS
Experimental: Part 2 Double-Blind Creon AAPIS / Creon; After receiving open-label currently marketed Creon DR capsules during a pre-randomization period, participants receive double-blind Creon DR capsules manufactured at an alternate active pharmaceutical ingredient site (Creon AAPIS) in treatment period 1, followed by double-blind Creon DR capsules in treatment period 2. Participants also receive open-label currently marketed Creon DR for an interval of up to 28 days between periods 1 and 2, and during a 30-day follow-up period after period 2.	Drug: Pancrelipase; Delayed release capsules; Other Names: Creon; ABT-SLV-245; Creon AAPIS
Experimental: Part 2 Double-Blind Creon / Creon AAPIS; After receiving open-label currently marketed Creon DR capsules during a pre-randomization period, participants receive double-blind Creon DR capsules in treatment period 1, followed by double-blind Creon AAPIS in treatment period 2. Participants also receive open-label currently marketed Creon DR for an interval of up to 28 days between periods 1 and 2, and during a 30-day follow-up period after period 2.	Drug: Pancrelipase; Delayed release capsules; Other Names: Creon; ABT-SLV-245; Creon AAPIS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: ABBVIE INC., AbbVie

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): October 23, 2019
• Primary Completion (Actual): July 11, 2022
• Study Completion (Actual): July 11, 2022

Study Registration Dates

• First Submitted: April 18, 2019
• First Submitted That Met QC Criteria: April 22, 2019
• First Posted (Actual): April 23, 2019

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Cystic Fibrosis; Pancrelipase; Creon; Exocrine Pancreatic Insufficiency (EPI); ABT-SLV-245
• 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: M16-111; 2017-000578-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes