Cystic FibrosisPhase 4NCT03924947
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 testing Pancrelipase in people with Cystic Fibrosis, run by AbbVie at 13 sites in United States.
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… Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Pancrelipase
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 13 sitesUnited States
- Study dates
- 23 Oct 2019to 11 Jul 2022
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
UH Cleveland Medical Center /ID# 206095
Cleveland, Ohio, 44106
Cleveland Clinic Main Campus /ID# 212853
Cleveland, Ohio, 44195
Nationwide Children's Hospital /ID# 225628
Columbus, Ohio, 43205-2664
University of Iowa Hospitals and Clinics /ID# 164551
Iowa City, Iowa, 52242
Nemours Children's Health System /ID# 164553
Jacksonville, Florida, 32207
University of Southern California /ID# 164571
Los Angeles, California, 90033
Vanderbilt University Medical Center /ID# 213434
Nashville, Tennessee, 37232-0011
The Cystic Fibrosis Institute /ID# 210757
Northfield, Illinois, 60093
Central FL Pulmonary Orlando /ID# 164558
Orlando, Florida, 32803
Children's Hospital of Philadelphia - Main /ID# 208114
Philadelphia, Pennsylvania, 19104-4319
Virginia Commonwealth University Medical Center Main Hospital /ID# 164574
Richmond, Virginia, 23219
Landon Pediatric Foundation /ID# 215411
Ventura, California, 93003-3099
Via Christi Research /ID# 214266
Wichita, Kansas, 67214-2878
About this study
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
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
- Being tested
- Pancrelipase
- Keywords
- Cystic Fibrosis, Creon, Pancrelipase, ABT-SLV-245, Exocrine Pancreatic Insufficiency (EPI)
- Medical subject headings
- Cystic Fibrosis, Exocrine Pancreatic Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PancrelipaseDrug
Also called Creon, ABT-SLV-245, Creon MP
Delayed release capsules
PancrelipaseDrug
Also called Creon, ABT-SLV-245, Creon AAPIS
Delayed release capsules
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Pancrelipase |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: Up to Day 8 of each DB treatment period
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: Up to Day 8 of each DB treatment period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2019
- Study start23 Oct 2019
- Primary completion11 Jul 2022
- Study completion11 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by AbbVieThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- AbbVie
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- ABBVIE INC., Study director, AbbVie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03924947
- Sponsor's protocol ID
- M16-111
- Other IDs
- 2017-000578-12, 2017
- Status last verified
- Sep 2023
- First submitted
- 18 Apr 2019
- Last updated
- 28 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03924947
- Acronym / sponsor ID
- M16-111
- Conditions
- Cystic Fibrosis
- Keywords
- Cystic Fibrosis, Creon, Pancrelipase, ABT-SLV-245, Exocrine Pancreatic Insufficiency (EPI)
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- AbbVieIndustry (pharma, biotech, devices)
- Study start
- 23 Oct 2019 (actual)
- Primary completion
- 11 Jul 2022 (actual)
- Study completion
- 11 Jul 2022 (actual)
- First posted
- 23 Apr 2019 (actual)
- Results
- Posted 28 Sep 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1 Double-Blind Creon MP / Creon | Experimental | Drug: PancrelipaseAfter 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. |
| Part 1 Double-Blind Creon / Creon MP | Experimental | Drug: PancrelipaseAfter 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. |
| Part 2 Double-Blind Creon AAPIS / Creon | Experimental | Drug: PancrelipaseAfter 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. |
| Part 2 Double-Blind Creon / Creon AAPIS | Experimental | Drug: PancrelipaseAfter 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. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Participant has a documented diagnosis of Cystic Fibrosis (CF) confirmed by:
- 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.
Key exclusion criteria (6 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PancrelipaseAlso: Creon, ABT-SLV-245, Creon MPDelayed release capsules | Drug | Part 1 Double-Blind Creon / Creon MP, Part 1 Double-Blind Creon MP / Creon |
| PancrelipaseAlso: Creon, ABT-SLV-245, Creon AAPISDelayed release capsules | Drug | Part 2 Double-Blind Creon / Creon AAPIS, Part 2 Double-Blind Creon AAPIS / Creon |
Primary outcome
Part 1 Coefficient of Fat Absorption (CFA)
Time frame: Up to Day 8 of each DB treatment period
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.
Part 2 Coefficient of Fat Absorption (CFA)
Time frame: Up to Day 8 of each DB treatment period
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.
3 secondary outcomes
Coefficient of Nitrogen Absorption (CNA)
Time frame: Up to Day 8 of each DB treatment period
Stool Fat
Time frame: Up to Day 8 of each DB treatment period
Stool Weight
Time frame: Up to Day 8 of each DB treatment period
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
ABBVIE INC. study director
AbbVie
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Pancrelipase in people with Cystic Fibrosis, run by AbbVie at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Part 1 Coefficient of Fat Absorption (CFA) (time frame: Up to Day 8 of each DB treatment period). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2023.