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.

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 Of the 19 patients who had informed consent from their parent/legally acceptable representative, one was withdrawn as a screen failure and was excluded from the safety and efficacy analyses; thus, 18 patients completed the study.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.