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.
*Louisiana State University and Children's Hospital, New Orleans, LA
†Nationwide Children's Hospital, Columbus, OH
‡Boys Town National Research Hospital, Boys Town, NE
§Digestive Healthcare Center, Hillsborough, NJ
||Sucampo Pharmaceuticals, Zug, Switzerland and Bethesda, MD.
Address correspondence and reprint requests to Paul E. Hyman, MD, Department of Pediatrics, Children's Hospital, 200 Henry Clay Avenue, New Orleans, LA 70118 (e-mail: email@example.com).
Received 4 February, 2013
Accepted 27 August, 2013
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http://www.clinicaltrials.gov registration no.: NCT00452335.
This study was financially supported by Sucampo Pharma Americas, and Takeda Pharmaceuticals. Editorial assistance for manuscript preparation was funded by Takeda Pharmaceuticals, and was provided by Craig D. Albright, PhD, and Michael J. Theisen, PhD, of Complete Healthcare Communications.
P.E.H. was a consultant to Sucampo Pharma Americas. C.D. received research support from Takeda Pharmaceuticals, relative to performing this study and has received an unrestricted educational grant from Sucampo Pharma Americas. L.L.P. received research support from Sucampo Pharma Americas, relative to performing this study. N.N.Y. received research support from Sucampo Pharma Americas, relative to performing this study. R.U. is the president and a director of Sucampo AG, is an employee of Sucampo Pharma Americas, and is a shareholder in Sucampo Pharmaceuticals.