Table 2.
Clinical trials of pancrelipase products approved by the US Food and Drug Administration for treatment of pancreatic exocrine insufficiency
| Drug | Study | Study design/duration/number of subjects | Disease | Results | Adverse effects | Evidence level |
|---|---|---|---|---|---|---|
| Creon® | Safdi et al32 | DBRPC, 2 weeks, 27 adults, (Creon, n = 14; placebo, n = 13) | Chronic pancreatitis | Change in CFA was significantly greater with pancrelipase versus placebo (36.7% and 12.1%); tool consistency/frequency, and fat excretion improved significantly in pancrelipase-treated patients | Six TEAEs occurred in 3 subjects treated with pancrelipase treatment versus 11 TEAEs in 5 subjects treated with placebo; there was no evidence of hyperuricemia |
1 |
| Whitcomb et al33 | DBRPC, 1 week, 54 adults, (Creon, n = 25; placebo, n = 29) | Chronic pancreatitis or pancreatic surgery | Changes from baseline in CFA (31.9% versus 8.7%; P < 0.0001) and CAN (35.2% versus 8.9%; P = 0.0005) were significantly greater with pancrelipase versus placebo | TEAEs were reported in 5 patients (20.0%) treated with pancrelipase versus 6 patients (20.7%) treated with placebo; the most common events were gastrointestinal events and metabolism/nutrition disorders | 1 | |
| Gubergrits et al34 | Open-label, 6 months 48 adults | Chronic pancreatitis or pancreatic surgery | Body weight increased by 2.7 ± 3.4 kg (P < 0.0001) and daily stool frequency decreased by −1.0 ± 1.3 (P < 0.001); increase in body weight was greater in lean patients (BMI < 18.5 kg/m2) than in patients with a BMI > 18.5 kg/m2 | Four patients (7.8%) experienced treatment-related AEs | 3 | |
| Stern et al41 | DBRPC, 1 week, 36 adults, (Creon, n = 18; placebo, n = 18), 38 pediatric/adolescent patients (Creon, n = 18; placebo, n = 20) | Cystic fibrosis | CFA decreased significantly (P < 0.001) with placebo (adults, 36.9%; pediatric/adolescents, 34.9%) from the open-label to double-blind phase of the study, while no change was observed in pancrelipase-treated patients (adults, 2%; pediatric/adolescents, 3.25%) | One serious AE occurred, ie, hospitalization for pulmonary exacerbation. More patients treated with placebo (adults, 67%; pediatric/adolescents, 70%) reported TEAEs than patients treated with pancrelipase (adults, 39%; pediatric/adolescents, 61%) |
1 | |
| Trapnell et al42 | DBRPC, 5-day, two-way crossover, 32 patients, (Creon, n = 16; placebo, n = 16) | Cystic fibrosis | Mean CFA (88.6% versus 49.6%; P < 0.01) and CNA (85.1% versus 49.9%; P < 0.001) were significantly greater with pancrelipase versus placebo | Symptom improvement was greater with pancrelipase than placebo; fewer patients treated with pancrelipase (18.8%) reported TEAEs than patients treated with placebo (38.7%); the most common TEAEs were gastrointestinal disorders (eg, abdominal pain and flatulence) |
1 | |
| Colombo et al43 | Open-label, 2 weeks, 12 infants | Cystic fibrosis | Pancrelipase significantly increased mean CFA from 58.0% at baseline to 84.7% (P = 0.0013); pancrelipase also significantly decreased mean stool fat excretion (from 13.3 to 5.3 g/day; P = 0.001) | Pancrelipase was well tolerated and decreased fat malabsorption; no serious AEs were reported | 3 | |
| Graff et al45 | DBRPC, 5 days, two-way crossover, 16 children aged 7–11 years | Cystic fibrosis | Mean (SE) CFA was significantly greater with pancrelipase versus placebo (82.8% [2.7%] versus 47.4% [2.7%]; P < 0.001); pancrelipase significantly improved stool fat, weight, and nitrogen, and significantly reduced daily stool frequency (all, P < 0.001) | TEAEs were reported in 5 patients (29.4%) treated with pancrelipase and in 9 patients (56.3%) treated with placebo; the most common AEs were gastrointestinal disorders; there were no serious AEs | 1 | |
| Zenpep® | Toskes et al35 | DBR, dose-response, crossover, ≤6 days 72 adults (available CFA values) | Chronic pancreatitis | CFA was higher in patients treated with low-dose (88.9%) and high-dose (89.9%) pancrelipase versus placebo (82%; P < 0.001; n = 72) with no difference between doses (P = 0.228); CNA (P < 0.001), body weight (P ≤ 0.021), and BMI (P ≤ 0.020) also increased with both doses of pancrelipase compared with baseline | Percentage of days with PEI symptoms decreased with both doses | 1 |
| Wooldridge et al44 | DBRPC, crossover 1week, open-label, 2 weeks, 33 adults | Cystic fibrosis | CFA (88.3% versus 62.8%; P < 0.001) and CNA (87.2% versus 65.7%; P < 0.001) were significantly greater with pancrelipase versus placebo | Nineteen patients (56%) treated with pancrelipase and 16 patients (50%) treated with placebo experienced ≥1 TEAE; there were no serious TEAEs | 1 | |
| Pancreaze® | Trapnell et al46 | DBRPC, 1 week 26 adults and 14 pediatric patients (Pancreaze, n = 20; placebo, n = 20) | Cystic fibrosis | Mean changes in CFA (−1.5% ± 5.9% versus −34.1% ± 23.0%; P < 0.001) and CNA (1.3% ± 4.7% versus −26.5% ± 15.3%; P < 0.001) were significantly smaller with pancrelipase versus placebo | TEAEs were reported in 8 patients (40%) treated with pancrelipase and in 12 patients (60%) treated with placebo; the most common AEs were gastrointestinal disorders; no unexpected AEs were reported | 2 |
Notes: CFA (%) = [(fat intake grams − fat exertion grams)/fat intake grams] × 100; CNA (%) = [(nitrogen intake grams − nitrogen exertion grams)/nitrogen intake grams] × 100.
Abbreviations: DBRPC, double-blind, randomized, placebo-controlled trial; DBR, double-blind, randomized trial; TEAEs, treatment-emergent adverse events; AE, adverse event; CFA, coefficient of fat absorption; CNA, coefficient of nitrogen absorption; BMI, body mass index; SE, standard error of the mean.