TY - JOUR
T1 - Lubiprostone for Pediatric Functional Constipation: Randomized, Controlled, Double-Blind Study With Long-term Extension
AU - Benninga, Marc A.
AU - Hussain, Sunny Z.
AU - Sood, Manu R.
AU - Nurko, Samuel
AU - Hyman, Paul
AU - Clifford, Robert A.
AU - O'Gorman, Molly
AU - Losch-Beridon, Taryn
AU - Mareya, Shadreck
AU - Lichtlen, Peter
AU - di Lorenzo, Carlo
N1 - Funding Information: Funding This study was supported by Takeda Development Center Americas, Inc, Lexington, MA and Mallinckrodt Pharmaceuticals, Bedminster, NJ . While the sponsors were involved with study design, analysis, and interpretation of the data, the decision to submit the manuscript was the sole decision of the authors. Publisher Copyright: © 2021 AGA Institute
PY - 2021
Y1 - 2021
N2 - 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, placebo-controlled, 12-week study evaluating the efficacy and safety of lubiprostone 12 μg twice daily (BID) and 24 μg 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 = .2245). Both the 12-μg BID and 24-μg 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. (ClinicalTrials.gov: Number: NCT02042183; Number: NCT02138136).
AB - 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, placebo-controlled, 12-week study evaluating the efficacy and safety of lubiprostone 12 μg twice daily (BID) and 24 μg 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 = .2245). Both the 12-μg BID and 24-μg 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. (ClinicalTrials.gov: Number: NCT02042183; Number: NCT02138136).
KW - Clinical Trial
KW - Defecation
KW - Incontinence
KW - Stools
UR - http://www.scopus.com/inward/record.url?scp=85111914477&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.cgh.2021.04.005
DO - https://doi.org/10.1016/j.cgh.2021.04.005
M3 - Article
C2 - 33838349
SN - 1542-3565
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
ER -