Trial Outcomes & Findings for Efficacy and Safety Study of Creon IR in Subjects With Pancreatic Exocrine Insufficiency Due to Cystic Fibrosis (NCT NCT02415959)
NCT ID: NCT02415959
Last Updated: 2016-04-04
Results Overview
CFA is calculated from fat intake and fat excretion, according to the formula: CFA (%) = 100 \[fat intake - fat excretion\] / fat intake
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
70 participants
Primary outcome timeframe
End of the 6 to 7 days double-blind treatment period
Results posted on
2016-04-04
Participant Flow
Participant milestones
| Measure |
Creon IR Low Dose
Creon IR 300 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 30,000 lipase units)
Creon IR
|
Creon IR Medium Dose
Creon IR 1,200 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 120,000 lipase units)
Creon IR
|
Creon IR High Dose
Creon IR 2,400 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 240,000 lipase units)
Creon IR
|
Creon IR Maximum Dose
Creon IR 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon IR
|
Creon® (DR/GR)
Creon® (DR/GR) 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon® (DR/GR)
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
14
|
14
|
14
|
14
|
14
|
|
Overall Study
COMPLETED
|
14
|
13
|
14
|
13
|
14
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
0
|
1
|
0
|
Reasons for withdrawal
| Measure |
Creon IR Low Dose
Creon IR 300 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 30,000 lipase units)
Creon IR
|
Creon IR Medium Dose
Creon IR 1,200 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 120,000 lipase units)
Creon IR
|
Creon IR High Dose
Creon IR 2,400 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 240,000 lipase units)
Creon IR
|
Creon IR Maximum Dose
Creon IR 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon IR
|
Creon® (DR/GR)
Creon® (DR/GR) 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon® (DR/GR)
|
|---|---|---|---|---|---|
|
Overall Study
Adverse Event
|
0
|
1
|
0
|
0
|
0
|
|
Overall Study
Protocol Violation
|
0
|
0
|
0
|
1
|
0
|
Baseline Characteristics
Efficacy and Safety Study of Creon IR in Subjects With Pancreatic Exocrine Insufficiency Due to Cystic Fibrosis
Baseline characteristics by cohort
| Measure |
Creon IR Low Dose
n=14 Participants
Creon IR 300 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 30,000 lipase units)
Creon IR
|
Creon IR Medium Dose
n=14 Participants
Creon IR 1,200 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 120,000 lipase units)
Creon IR
|
Creon IR High Dose
n=14 Participants
Creon IR 2,400 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 240,000 lipase units)
Creon IR
|
Creon IR Maximum Dose
n=14 Participants
Creon IR 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon IR
|
Creon® (DR/GR)
n=14 Participants
Creon® (DR/GR) 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon® (DR/GR)
|
Total
n=70 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
4 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
26 Participants
n=10 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
10 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
44 Participants
n=10 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
|
Age, Continuous
|
24.7 years
STANDARD_DEVIATION 7.6 • n=5 Participants
|
22.9 years
STANDARD_DEVIATION 8.5 • n=7 Participants
|
22.0 years
STANDARD_DEVIATION 7.3 • n=5 Participants
|
19.7 years
STANDARD_DEVIATION 8.4 • n=4 Participants
|
22.6 years
STANDARD_DEVIATION 7.1 • n=21 Participants
|
22.4 years
STANDARD_DEVIATION 7.7 • n=10 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
33 Participants
n=10 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
37 Participants
n=10 Participants
|
|
Region of Enrollment
Hungary
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
3 participants
n=4 Participants
|
3 participants
n=21 Participants
|
15 participants
n=10 Participants
|
|
Region of Enrollment
Czech Republic
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
1 participants
n=5 Participants
|
1 participants
n=4 Participants
|
1 participants
n=21 Participants
|
5 participants
n=10 Participants
|
|
Region of Enrollment
Poland
|
6 participants
n=5 Participants
|
6 participants
n=7 Participants
|
6 participants
n=5 Participants
|
6 participants
n=4 Participants
|
6 participants
n=21 Participants
|
30 participants
n=10 Participants
|
|
Region of Enrollment
Spain
|
4 participants
n=5 Participants
|
4 participants
n=7 Participants
|
4 participants
n=5 Participants
|
4 participants
n=4 Participants
|
4 participants
n=21 Participants
|
20 participants
n=10 Participants
|
PRIMARY outcome
Timeframe: End of the 6 to 7 days double-blind treatment periodPopulation: Full Analysis set. Four randomized subjects excluded because no post-baseline efficacy data (two non-completers and two subjects whose stools were mixed-up with each other at the analytical laboratory).
CFA is calculated from fat intake and fat excretion, according to the formula: CFA (%) = 100 \[fat intake - fat excretion\] / fat intake
Outcome measures
| Measure |
Creon IR Low Dose
n=13 Participants
Creon IR 300 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 30,000 lipase units)
Creon IR
|
Creon IR Medium Dose
n=13 Participants
Creon IR 1,200 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 120,000 lipase units)
Creon IR
|
Creon IR High Dose
n=14 Participants
Creon IR 2,400 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 240,000 lipase units)
Creon IR
|
Creon IR Maximum Dose
n=13 Participants
Creon IR 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon IR
|
Creon® (DR/GR)
n=13 Participants
Creon® (DR/GR) 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon® (DR/GR)
|
|---|---|---|---|---|---|
|
Coefficient of Fat Absorption (CFA)
|
71.0 percentage of fat intake
Standard Deviation 12.4
|
70.9 percentage of fat intake
Standard Deviation 13.9
|
71.8 percentage of fat intake
Standard Deviation 15.2
|
75.9 percentage of fat intake
Standard Deviation 9.2
|
92.3 percentage of fat intake
Standard Deviation 3.7
|
SECONDARY outcome
Timeframe: End of the 6 to 7 days double-blind treatment periodPopulation: Full Analysis set. Four randomized subjects excluded because no post-baseline efficacy data (two non-completers and two subjects whose stools were mixed-up with each other at the analytical laboratory).
CNA is calculated from nitrogen intake and nitrogen excretion, according to the formula: CNA (%) = 100 \[nitrogen intake - nitrogen excretion\] / nitrogen intake)
Outcome measures
| Measure |
Creon IR Low Dose
n=13 Participants
Creon IR 300 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 30,000 lipase units)
Creon IR
|
Creon IR Medium Dose
n=13 Participants
Creon IR 1,200 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 120,000 lipase units)
Creon IR
|
Creon IR High Dose
n=14 Participants
Creon IR 2,400 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 240,000 lipase units)
Creon IR
|
Creon IR Maximum Dose
n=13 Participants
Creon IR 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon IR
|
Creon® (DR/GR)
n=13 Participants
Creon® (DR/GR) 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon® (DR/GR)
|
|---|---|---|---|---|---|
|
Coefficient of Nitrogen Absorption (CNA)
|
71.0 percentage of nitrogen intake
Standard Deviation 10.0
|
73.2 percentage of nitrogen intake
Standard Deviation 6.4
|
76.2 percentage of nitrogen intake
Standard Deviation 8.1
|
79.9 percentage of nitrogen intake
Standard Deviation 7.3
|
84.8 percentage of nitrogen intake
Standard Deviation 4.3
|
SECONDARY outcome
Timeframe: End of the 6 to 7 days double-blind treatment periodPopulation: Full Analysis set. Four randomized subjects excluded because no post-baseline efficacy data (two non-completers and two subjects whose stools were mixed-up with each other at the analytical laboratory).
Total amount of fat excreted during the stool collection period in grams.
Outcome measures
| Measure |
Creon IR Low Dose
n=13 Participants
Creon IR 300 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 30,000 lipase units)
Creon IR
|
Creon IR Medium Dose
n=13 Participants
Creon IR 1,200 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 120,000 lipase units)
Creon IR
|
Creon IR High Dose
n=14 Participants
Creon IR 2,400 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 240,000 lipase units)
Creon IR
|
Creon IR Maximum Dose
n=13 Participants
Creon IR 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon IR
|
Creon® (DR/GR)
n=13 Participants
Creon® (DR/GR) 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon® (DR/GR)
|
|---|---|---|---|---|---|
|
Stool Fat Content
|
87.5 gram per 72 hours
Standard Deviation 37.5
|
87.1 gram per 72 hours
Standard Deviation 41.0
|
84.1 gram per 72 hours
Standard Deviation 44.9
|
73.0 gram per 72 hours
Standard Deviation 28.2
|
23.5 gram per 72 hours
Standard Deviation 11.3
|
SECONDARY outcome
Timeframe: End of the 6 to 7 days double-blind treatment periodPopulation: Full Analysis set. Four randomized subjects excluded because no post-baseline efficacy data (two non-completers and two subjects whose stools were mixed-up with each other at the analytical laboratory).
Total amount of stool weight during the collection period in grams
Outcome measures
| Measure |
Creon IR Low Dose
n=13 Participants
Creon IR 300 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 30,000 lipase units)
Creon IR
|
Creon IR Medium Dose
n=13 Participants
Creon IR 1,200 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 120,000 lipase units)
Creon IR
|
Creon IR High Dose
n=14 Participants
Creon IR 2,400 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 240,000 lipase units)
Creon IR
|
Creon IR Maximum Dose
n=13 Participants
Creon IR 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon IR
|
Creon® (DR/GR)
n=13 Participants
Creon® (DR/GR) 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon® (DR/GR)
|
|---|---|---|---|---|---|
|
Stool Weight
|
889.0 gram per 72 hours
Standard Deviation 294.2
|
905.3 gram per 72 hours
Standard Deviation 225.7
|
793.8 gram per 72 hours
Standard Deviation 279.8
|
755.7 gram per 72 hours
Standard Deviation 383.2
|
545.7 gram per 72 hours
Standard Deviation 256.3
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From randomization to end of Double Blind period plus 1 day, i.e. up to 7/8 daysTreatment emergent adverse events will be summarized per treatment group
Outcome measures
| Measure |
Creon IR Low Dose
n=14 Participants
Creon IR 300 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 30,000 lipase units)
Creon IR
|
Creon IR Medium Dose
n=14 Participants
Creon IR 1,200 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 120,000 lipase units)
Creon IR
|
Creon IR High Dose
n=14 Participants
Creon IR 2,400 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 240,000 lipase units)
Creon IR
|
Creon IR Maximum Dose
n=14 Participants
Creon IR 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon IR
|
Creon® (DR/GR)
n=14 Participants
Creon® (DR/GR) 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon® (DR/GR)
|
|---|---|---|---|---|---|
|
Treatment Emergent Adverse Events
|
10 participants
|
9 participants
|
7 participants
|
9 participants
|
7 participants
|
Adverse Events
Creon IR Low Dose
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Creon IR Medium Dose
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Creon IR High Dose
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Creon IR Maximum Dose
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
Creon® (DR/GR)
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Creon IR Low Dose
n=14 participants at risk
Creon IR 300 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 30,000 lipase units)
Creon IR
|
Creon IR Medium Dose
n=14 participants at risk
Creon IR 1,200 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 120,000 lipase units)
Creon IR
|
Creon IR High Dose
n=14 participants at risk
Creon IR 2,400 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 240,000 lipase units)
Creon IR
|
Creon IR Maximum Dose
n=14 participants at risk
Creon IR 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon IR
|
Creon® (DR/GR)
n=14 participants at risk
Creon® (DR/GR) 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon® (DR/GR)
|
|---|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
infective pulmonary exacerbation due to CF
|
0.00%
0/14
|
0.00%
0/14
|
7.1%
1/14 • Number of events 1
|
0.00%
0/14
|
0.00%
0/14
|
Other adverse events
| Measure |
Creon IR Low Dose
n=14 participants at risk
Creon IR 300 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 30,000 lipase units)
Creon IR
|
Creon IR Medium Dose
n=14 participants at risk
Creon IR 1,200 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 120,000 lipase units)
Creon IR
|
Creon IR High Dose
n=14 participants at risk
Creon IR 2,400 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 240,000 lipase units)
Creon IR
|
Creon IR Maximum Dose
n=14 participants at risk
Creon IR 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon IR
|
Creon® (DR/GR)
n=14 participants at risk
Creon® (DR/GR) 4,000 Ph. Eur. U lipase/g fat, proportionally administered five times daily (during 3 meals and 2 snacks) for 6 to 7 days (target total daily dose of 400,000 lipase units)
Creon® (DR/GR)
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
42.9%
6/14 • Number of events 6
|
57.1%
8/14 • Number of events 8
|
42.9%
6/14 • Number of events 6
|
28.6%
4/14 • Number of events 4
|
14.3%
2/14 • Number of events 2
|
|
Gastrointestinal disorders
Flatulence
|
14.3%
2/14 • Number of events 2
|
14.3%
2/14 • Number of events 2
|
42.9%
6/14 • Number of events 6
|
21.4%
3/14 • Number of events 3
|
14.3%
2/14 • Number of events 2
|
|
Gastrointestinal disorders
Abdominal distension
|
21.4%
3/14 • Number of events 3
|
21.4%
3/14 • Number of events 3
|
0.00%
0/14
|
14.3%
2/14 • Number of events 2
|
7.1%
1/14 • Number of events 1
|
|
Gastrointestinal disorders
Diarrhea
|
28.6%
4/14 • Number of events 4
|
28.6%
4/14 • Number of events 4
|
14.3%
2/14 • Number of events 2
|
7.1%
1/14 • Number of events 1
|
7.1%
1/14 • Number of events 1
|
|
Gastrointestinal disorders
faeces soft
|
14.3%
2/14 • Number of events 2
|
7.1%
1/14 • Number of events 1
|
7.1%
1/14 • Number of events 1
|
7.1%
1/14 • Number of events 1
|
14.3%
2/14 • Number of events 2
|
|
Nervous system disorders
Headache
|
7.1%
1/14 • Number of events 1
|
0.00%
0/14
|
7.1%
1/14 • Number of events 1
|
7.1%
1/14 • Number of events 1
|
0.00%
0/14
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place