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

NCT03924947 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: M16-1112017-000578-12
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 13

Brief 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.

Conditions

Cystic Fibrosis

Keywords

Cystic Fibrosis; Creon; Pancrelipase; ABT-SLV-245; Exocrine Pancreatic Insufficiency (EPI)

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Coefficient of Nitrogen Absorption (CNA)

  Up to Day 8 of each DB treatment period

• Stool Fat

  Up to Day 8 of each DB treatment period

• Stool Weight

  Up to Day 8 of each DB treatment period

Study Arms (4)

Part 1 Double-Blind Creon MP / Creon

EXPERIMENTAL

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

Part 1 Double-Blind Creon / Creon MP

EXPERIMENTAL

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

Part 2 Double-Blind Creon AAPIS / Creon

EXPERIMENTAL

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

Part 2 Double-Blind Creon / Creon AAPIS

EXPERIMENTAL

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

Interventions

Pancrelipase DRUG

Delayed release capsules

Also known as: Creon, ABT-SLV-245, Creon MP

Part 1 Double-Blind Creon / Creon MP; Part 1 Double-Blind Creon MP / Creon

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AbbVie: lead

Study Sites (13)

University of Southern California /ID# 164571

Los Angeles, California, 90033, United States

Location

Landon Pediatric Foundation /ID# 215411

Ventura, California, 93003-3099, United States

Location

Nemours Children's Health System /ID# 164553

Jacksonville, Florida, 32207, United States

Location

Central FL Pulmonary Orlando /ID# 164558

Orlando, Florida, 32803, United States

Location

The Cystic Fibrosis Institute /ID# 210757

Northfield, Illinois, 60093, United States

Location

University of Iowa Hospitals and Clinics /ID# 164551

Iowa City, Iowa, 52242, United States

Location

Via Christi Research /ID# 214266

Wichita, Kansas, 67214-2878, United States

Location

UH Cleveland Medical Center /ID# 206095

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Main Campus /ID# 212853

Cleveland, Ohio, 44195, United States

Location

Nationwide Children's Hospital /ID# 225628

Columbus, Ohio, 43205-2664, United States

Location

Children's Hospital of Philadelphia - Main /ID# 208114

Philadelphia, Pennsylvania, 19104-4319, United States

Location

Vanderbilt University Medical Center /ID# 213434

Nashville, Tennessee, 37232-0011, United States

Location

Virginia Commonwealth University Medical Center Main Hospital /ID# 164574

Richmond, Virginia, 23219, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Cystic Fibrosis; Exocrine Pancreatic Insufficiency

Interventions

Pancrelipase

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Intervention Hierarchy (Ancestors)

Lipase; Carboxylic Ester Hydrolases; Esterases; Hydrolases; Enzymes; Enzymes and Coenzymes; Pancreatic Extracts; Tissue Extracts; Complex Mixtures

Results Point of Contact

• Title: Global Medical Services
• Organization: AbbVie

abbvieclinicaltrials@abbvie.com

800-633-9110

Study Officials

• ABBVIE INC.

  AbbVie

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 18, 2019
• First Posted: April 23, 2019
• Study Start: October 23, 2019
• Primary Completion: July 11, 2022
• Study Completion: July 11, 2022
• Last Updated: September 28, 2023
• Results First Posted: September 28, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• 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/

Locations

US (13)