Safety of Lubiprostone in Pediatric Patients With Functional Constipation: A Nonrandomized, Open-Label Trial

Abstract

Objectives: Pediatric functional constipation (PFC) affects up to 30% of children. Current treatments often do not sustain symptomatic relief. Lubiprostone is a locally acting chloride channel activator that promotes fluid secretion into the small bowel without affecting serum electrolyte concentrations. We assessed the safety/tolerability of oral lubiprostone as treatment for PFC in a 24-week study.

Methods: This phase 3 open-label safety trial conducted from April-November 2016 at 13 US sites included patients (ages 6-17 years) diagnosed with PFC (Rome III criteria). Patients <50 and ≥50 kg received lubiprostone 12 or 24 mcg twice daily, respectively, for 24 weeks. Safety endpoints included incidence of treatment-emergent adverse events (TEAEs) and changes from baseline in clinical laboratory parameters and vital signs.

Results: Overall, 87 patients receiving lubiprostone, 64.3% (36/56) in the 12-mcg group and 54.8% (17/31) in the 24-mcg group, completed the study. Of 12 TEAEs leading to discontinuation, only upper abdominal pain occurred in >1 patient. TEAEs were mostly mild in intensity, with gastrointestinal disorders (diarrhea, vomiting) most frequently reported. No safety concerns were found in vital signs, abbreviated physical examinations, and laboratory tests. Subgroup analyses assessed an impact of age, sex, and race categories on TEAEs and treatment-related adverse events. Mean investigators' assessments of treatment effectiveness (scale of 0-4) for lubiprostone 12- and 24-mcg groups, respectively, were 2.8 and 2.9 at week 12, and 2.7 and 2.2 at week 24.

Conclusions: Lubiprostone was well tolerated in the pediatric population. The incidence of TEAEs was comparable to that observed in previous clinical trials and in adults.

FIGURE 1

Overview of treatment-emergent adverse events (safety population). ^aTEAE is any event with an onset date on or after the first dose of study medication and with an onset date no more than 7 days after the last dose of study medication. BID = twice daily; n = subgroup of population; TEAE = treatment-emergent adverse event.

FIGURE 2

Treatment-related adverse events reported by ≥5% of patients or GI disorders reported in ≥3% of patients in either lubiprostone treatment group (safety population). GI disorders: diarrhea, nausea, upper abdominal pain, abdominal pain, abdominal distension. BID = twice daily; GI = gastrointestinal; n = subgroup of population; TRAE = treatment-related adverse event.