Objectives: Pediatric functional constipation is common; effective, easily administered treatment options are limited. Lubiprostone is an oral chloride channel protein-2 activator that stimulates gastrointestinal fluid secretion, softens stools, and facilitates bowel movements (BMs). We evaluated the safety and effectiveness of lubiprostone in children and adolescents with functional constipation.
Methods: Patients ≥12 kg, 17 years or younger, and with <3 spontaneous BMs (SBMs; ie, BMs that did not occur within 24 hours of rescue medication use) per week were enrolled at 22 US general pediatric and pediatric gastroenterology centers (January 2007-October 2008). Patients received 4 weeks of open-label lubiprostone at doses of 12 μg once daily (QD), 12 μg twice daily (BID), or 24 μg BID based on age and weight. The primary endpoint was SBM frequency during week 1 versus baseline.
Results: Of 127 enrolled patients, 124 were treated and analyzed (12 μg QD, n = 27; 12 μg BID, n = 65; 24 μg BID, n = 32), and 109 completed the study. The mean age of treated patients was 10.2 years (range 3-17 years); 65 were boys. Mean SBM frequency significantly increased compared with baseline at week 1 (3.1 vs. 1.5 SBMs/week, P < 0.0001). SBM frequency was improved significantly from baseline overall (P < 0.0001) and for individual dose groups (P ≤ 0.0062) during weeks 2, 3, and 4. Common (≥5%) adverse events included nausea (18.5%), vomiting (12.1%), diarrhea (8.1%), abdominal pain (7.3%), and headache (5.6%). Two patients experienced serious adverse events (unrelated abdominal pain; unrelated sickle cell crisis).
Conclusions: Lubiprostone was efficacious and well tolerated in children and adolescents with functional constipation.