Lubiprostone for Pediatric Functional Constipation: Randomized, Controlled, Double-Blind Study With Long-term Extension

Abstract

BACKGROUND & AIMS:Pediatric functional constipation (PFC) is a common problem in children that causes distress and presents treatment challenges to health care professionals. We conducted a randomized, placebo-controlled trial (study 1) in patients with PFC (6-17 years of age) to evaluate the efficacy and safety of lubiprostone, followed by an open-label extension for those who completed the placebo-controlled phase (study 2). METHODS:Study 1 (NCT02042183) was a phase 3, multicenter, randomized, double-blind, placebocontrolled, 12-week study evaluating the efficacy and safety of lubiprostone 12 mg twice daily (BID) and 24 mg BID. Study 2 (NCT02138136) was a phase 3, long-term, open-label extension of study 1. In both studies, lubiprostone doses were based on patients' weight. Efficacy was assessed solely based on study 1, with a primary endpoint of overall spontaneous bowel movement (SBM) response (increase of ‡1 SBM/wk vs baseline and ‡3 SBMs/wk for ‡9 weeks, including 3 of the final 4 weeks). RESULTS:606 patients were randomized to treatment (placebo: n [ 202; lubiprostone: n [ 404) in study 1. No statistically significant difference in overall SBM response rate was observed between the lubiprostone and placebo groups (18.5% vs 14.4%; P ¼ .2245). Both the 12-mg BID and 24-mg BID doses of lubiprostone were well tolerated in the double-blind and extension phases, with a safety profile consistent with that seen in adult studies. CONCLUSIONS:Lubiprostone did not demonstrate statistically significant effectiveness over placebo in children and adolescents with PFC but did demonstrate a safety profile similar to that in adults. (Clin-icalTrials.gov: Number: NCT02042183; Number: NCT02138136).

Safety of Lubiprostone in Pediatric Patients With Functional Constipation

“…In a separate lubiprostone study in PFC, following a 12-week treatment period, there was no statistically significant difference in the primary endpoint of overall spontaneous bowel movement (SBM) response rate between the lubiprostone and placebo groups (18.5% for lubiprostone vs 14.4% for placebo; treatment difference = 4.1%; P = 0.2245). Some of the secondary endpoints deemed clinically important in the FDA review (abdominal pain, painfulness of SBM, and frequency of incontinence episodes) were also assessed, but no statistically significant differences were observed after adjusting for multiple comparisons ( 23 ).…”

Functional Constipation and Dyssynergic Defecation in Children

“…The importance of withholding behavior in children has also been suggested as a potential explanation for the disappointing results of pediatric trials investigating novel pharmacological agents which have proven to be effective in adults, such as prucalopride and lubiprostone (67)(68)(69). Inclusion of children with severe withholding behavior may negatively affect study outcomes investigating pharmacological agents, if these agents do not target anorectal dysfunction.…”

The magnitude and management of functional constipation at pediatric gastroenterology clinics: A survey study of various countries

“…Recent multicenter randomized-controlled studies found, however, that prucalopride and lubiprostone were not more effective than placebo in children with FC. 29,30 It should be noted, however, that both studies were carried out in children with FC rather than CI.…”