NATIONAL HARBOR, MD. — Lubiprostone significantly improved spontaneous bowel movement frequency and associated symptoms in a multicenter, open-label study of 109 children with functional constipation.
Lubiprostone, which stimulates intestinal fluid secretion via chloride channel activation, is approved for the treatment of chronic idiopathic constipation in adults. This phase IV study assessed the safety and efficacy of oral lubiprostone in children and adolescents with functional constipation.
Lubiprostone offers the option of taking a small pill, as an alternative to drinking 240 mL or more of polyethylene glycol, Dr. Paul E. Hyman said at the annual meeting of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.
To qualify for the study, which was sponsored by Sucampo Pharmaceuticals Inc., potential participants had to be less than 18 years of age, at least 12 kg in weight, and capable of swallowing capsules without chewing. The children had to have fewer than three spontaneous bowel movements (SBMs) per week and meet at least one of the following criteria: at least half of the SBMs were hard or with at least moderate pain, or they had large-diameter stools once weekly or less.
A total of 124 children received lubiprostone, with the dosage based on weight: 27 received 12 mcg/day, 65 received 12 mcg twice a day, and 32 received 24 mcg twice a day. A total of 109 children completed the 4-week study. Each child served as his or her own control during a 2-week baseline period prior to the 4-week treatment.
In the intent-to-treat analysis, improvements in SBM frequency were significant in all dosage groups. Overall, there was a doubling, from 1.5 SBMs/week at baseline to approximately 3/week at weeks 1, 2, 3, and 4 of the study. There also were statistically significant reductions in straining and pain during SBMs beginning at week 1 and maintained through week 4, and significant improvement in consistency at all four time points, compared with baseline, said Dr. Hyman, professor of pediatrics and head of the division of gastroenterology in the department of pediatrics at Louisiana State University, New Orleans.
The percentage of patients using rescue medications—such as oral laxatives, suppositories, or enemas—after 3 days without defecation decreased from 29% during the 2-week baseline period to 10% during week 1, 22% during week 2, and 14% at weeks 3 and 4.
About half of the patients were full or moderate responders. The most common treatment-related adverse events were nausea (14.5%), vomiting (9%), and headache (3%), which diminished after the patients were advised to take lubiprostone with food.
Dr. Hyman is a consultant to Sucampo.