er in patients with lower no-treatment (placebo) CFA values than in patients with higher no-treatment (placebo) CFA values. There were no differences in response to Creon by age or gender, with similar responses to Creon observed in male and female patients, and in younger (under 18 years of age) and older patients.
The coefficient of nitrogen absorption (CNA) was determined by a 72-hour stool collection during both treatments, when nitrogen excretion was measured and nitrogen ingestion from a controlled diet was estimated (based on the assumption that proteins contain 16% nitrogen). Each patient's CNA during placebo treatment was used as their no-treatment CNA value.
In Study 1, mean CNA was 86% with Creon treatment compared to 49% with placebo treatment. The mean difference in CNA was 37 percentage points in favor of Creon treatment with 95% CI: (31, 42) and p<0.001.
In Study 2, mean CNA was 80% with Creon treatment compared to 45% with placebo treatment. The mean difference in CNA was 35 percentage points in favor of Creon treatment with 95% CI: (26, 45) and p<0.001.
Chronic Pancreatitis or Pancreatectomy
A randomized, double-blind, placebo-controlled, parallel group study was conducted in 54 adult patients, ages 32 to 75 years, with EPI due to chronic pancreatitis or pancreatectomy. The final analysis population was limited to 52 patients; 2 patients were excluded due to protocol violations. Ten patients had a history of pancreatectomy (7 were treated with Creon). In this study, patients received placebo for 5 days (run-in period), followed by pancreatic enzyme replacement therapy as directed by the investigator for 16 days; this was followed by randomization to Creon or matching placebo for 7 days of treatment (double-blind period). Only patients with CFA less than 80% in the run-in period were randomized to the double-blind period. The dose of Creon during the double-blind period was 72,000 lipase units per main meal (3 main meals) and 36,000 lipase units per snack (2 snacks). All patients consumed a high-fat diet (greater than or equal to 100 grams of fat per day) during the treatment period.
The CFA was determined by a 72-hour stool collection during the run-in and double-blind treatment periods, when both fat excretion and fat ingestion were measured. The mean change in CFA from the run-in period to the end of the double-blind period in the Creon and Placebo groups is shown in Table 3.
Table 3: Change in CFA in the Chronic Pancreatitis and Pancreatectomy Trial (Run-in Period to End of Double-Blind Period) *p<0.0001
Creon
n = 24 Placebo
n = 28
CFA [%]
Run-in Period (Mean, SD) 54 (19) 57 (21)
End of Double-Blind Period (Mean, SD) 86 (6) 66 (20)
Change in CFA * [%]
Run-in Period to End of Double-Blind Period (Mean, SD) 32 (18) 9 (13)
Treatment Difference (95% CI) 21 (14, 28)
Subgroup analyses of the CFA results showed that mean change in CFA was greater in patients with lower run-in period CFA values than in patients with higher run-in period CFA values. Only 1 of the patients with a history of total pancreatectomy was treated with Creon in the study. That patient had a CFA of 26% during the run-in period and a CFA of 73% at the end of the double-blind period. The remaining 6 patients with a history of partial pancreatectomy treated with Creon on the stu
