PMID- 20441244
OWN - NLM
STAT- MEDLINE
DCOM- 20100722
LR  - 20211020
IS  - 1173-2563 (Print)
IS  - 1173-2563 (Linking)
VI  - 30
IP  - 6
DP  - 2010
TI  - Safety and tolerability of a new formulation of pancrelipase delayed-release 
      capsules (CREON) in children under seven years of age with exocrine pancreatic 
      insufficiency due to cystic fibrosis: an open-label, multicentre, 
      single-treatment-arm study.
PG  - 351-64
LID - 10.2165/11533390-000000000-00000 [doi]
AB  - Exocrine pancreatic insufficiency (EPI) is a deficiency of digestive enzymes 
      caused by diseases such as cystic fibrosis (CF). Patients with EPI due to CF 
      require pancreatic enzyme replacement therapy (PERT) in order to maintain 
      adequate nutrition. A new formulation of pancrelipase delayed-release capsules 
      (CREON) recently received US FDA approval and has demonstrated efficacy and 
      safety in patients with CF aged > or =7 years. The objectives of this study were 
      to observe the safety and tolerability of new formulation pancrelipase 
      delayed-release capsules (study drug) versus the standard of care PERT (standard 
      therapy) in children aged <7 years with CF and EPI. Secondary objectives were to 
      assess the ease of accurate dosing of study drug, monitor clinical symptoms and 
      compare the efficacy of both treatments. This was an open-label, multicentre, 
      single-treatment-arm study in children aged <7 years with a confirmed diagnosis 
      of CF and EPI. After the screening period (approximately 14 days), all patients 
      entered a 3-day assessment period on their usual PERT (standard therapy), 
      followed by the study drug treatment phase (10-14 days; target dose 8000 lipase 
      units/kg bodyweight/day), which included a second 3-day assessment period. The 
      safety and tolerability of both treatments were documented by recording adverse 
      events (AEs). Clinical symptoms (mean daily stool frequency, abdominal pain, 
      stool consistency and flatulence) were monitored and ease of accurate dosing, as 
      judged by caregivers, was reported. Efficacy was determined by comparison of 
      percent stool fat in spot stool samples collected during both 3-day assessment 
      periods. Of the 19 patients who had informed consent from their parent/legally 
      acceptable representative, one was withdrawn as a screen failure and was excluded 
      from the safety and efficacy analyses; thus, 18 patients completed the study. The 
      median age (range) was 23 (4-71) months and 13 (72%) were male. During study drug 
      treatment, patients received a mean +/- SD dose in lipase units/kg bodyweight/day 
      of 7542 +/- 1335 versus 6966 +/- 3392 on standard therapy. Overall, nine (50%) 
      patients had at least one treatment-emergent AE (TEAE) whilst receiving either 
      treatment. All TEAEs in this study were reported as mild and none resulted in 
      patient discontinuation. The caregivers had a slight preference for study drug 
      over standard therapy in terms of ease of accurate dosing: six (33.3%) caregivers 
      thought the study drug was easier to dose while only one (5.6%) thought the study 
      drug was harder to dose than standard therapy. Clinical symptom assessment 
      results were similar between treatments. There was no clinically meaningful 
      difference (significance not tested) between study drug and standard therapy in 
      the mean +/- SD percent of stool fat: 28.1 +/- 9.9 and 27.9 +/- 8.9, 
      respectively. In this study in children aged <7 years with EPI due to CF, the new 
      formulation pancrelipase delayed-release capsules (CREON) were clinically 
      comparable with standard therapy in terms of safety, tolerability and efficacy.
FAU - Graff, Gavin R
AU  - Graff GR
AD  - Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA. 
      ggraff@hmc.psu.edu
FAU - McNamara, John
AU  - McNamara J
FAU - Royall, James
AU  - Royall J
FAU - Caras, Steven
AU  - Caras S
FAU - Forssmann, Kristin
AU  - Forssmann K
LA  - eng
PT  - Clinical Trial
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
PL  - New Zealand
TA  - Clin Drug Investig
JT  - Clinical drug investigation
JID - 9504817
RN  - 0 (Capsules)
RN  - 0 (Delayed-Action Preparations)
RN  - 0 (Gastrointestinal Agents)
RN  - 53608-75-6 (Pancrelipase)
SB  - IM
MH  - Capsules
MH  - Child, Preschool
MH  - Cystic Fibrosis/*complications
MH  - Delayed-Action Preparations
MH  - Enzyme Replacement Therapy/methods
MH  - Exocrine Pancreatic Insufficiency/*drug therapy/etiology
MH  - Female
MH  - Gastrointestinal Agents/administration & dosage/*adverse effects/therapeutic use
MH  - Humans
MH  - Infant
MH  - Male
MH  - Pancrelipase/administration & dosage/*adverse effects/therapeutic use
EDAT- 2010/05/06 06:00
MHDA- 2010/07/23 06:00
CRDT- 2010/05/06 06:00
PHST- 2010/05/06 06:00 [entrez]
PHST- 2010/05/06 06:00 [pubmed]
PHST- 2010/07/23 06:00 [medline]
AID - 1 [pii]
AID - 10.2165/11533390-000000000-00000 [doi]
PST - ppublish
SO  - Clin Drug Investig. 2010;30(6):351-64. doi: 10.2165/11533390-000000000-00000.