Lubiprostone in Children With Functional Constipation

A Multicentre, Randomised, Placebo-controlled, Double-blinded Study of the Efficacy, Safety, and Pharmacokinetics of Lubiprostone in Paediatric Subjects Aged ≥ 6 Years to < 18 Years With Functional Constipation

Study to determine if children (6-17 years old) with functional constipation will respond to being treated with lubiprostone for 12 weeks.

Study Overview

• Status: Completed
• Conditions: Constipation - Functional
• Intervention / Treatment: Drug: Lubiprostone; Drug: Placebo

Detailed Description

Dose administration details:

• Participants with a body weight <50 kg at baseline received Lubiprostone 12 mcg BID for 12 weeks. If the dose was safe but did not show any efficacy at Week 1, dosage was increased to 24 mcg BID.
• Participants with a body weight >50 kg at baseline received Lubiprostone 24 mcg BID for 12 weeks. If the dose was unsafe at Week 1, dosage was decreased to 12 mcg BID.

• Study Type: Interventional
• Enrollment (Actual): 606
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brussel, Belgium, 01090
    • Universitair Kinderziekenhuis Brussel
  • Leuven, Belgium, 03000
    • University Hospital Gasthuisberg
  • Montegnee, Belgium, 04420
    • CHC - Clinique Saint-Joseph
• Canada
  • Montreal, Canada, H3T 1C5
    • Sainte Justine University Health Center
  • Ontario
    • London, Ontario, Canada, N6C 2V5
      • London Health Sciences Centre
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 5N4
      • Centre de recherche du CHUS
• France
  • Bordeaux, France, 33000
    • CHU-Bordeaux
  • Bron, France, 69677
    • Groupe Hospitalier Est
  • Paris, France, 75012
    • Armand-Trousseau Teaching Hospital
  • Paris-Cedex, France, 75743
    • Hopital Necker
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Emma Children's Hospital
  • Breda, Netherlands, 4800 RK
    • Amphia ziekenhuis
  • Rotterdam, Netherlands, 3079 DZ
    • Maasstad Hospital Rotterdam
  • Zwolle, Netherlands, 8025 AB
    • Isala Klinieken
• Poland
  • Bialystok, Poland, 15-274
    • Medical University of Bialystok
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki
  • Krakow, Poland, 31-159
    • ATOPIA Poradnie Specjalistyczne
  • Lodz, Poland, 91-738
    • Medical University of Lodz
  • Lodz, Poland, 93-338
    • Szpital Pediatryczny ICZMP
  • Rzeszow, Poland, 35-210
    • Gabinet Lekarski Bartosc Korczowski
  • Warszaw, Poland, 00-632
    • Children's Memorial Health Institute
  • Warszaw, Poland, 04-730
    • Children's Memorial Health Institute
  • Warszawa, Poland, 01-231
    • Przychodnia Specjalistyczna PROSEN
• United Kingdom
  • Canterbury, United Kingdom, CT1 3NG
    • Kent and Canterbury Hospital
  • Darlington, United Kingdom, DL3 6HZ
    • Darlington Memorial Hospital
  • Glasgow, United Kingdom, G3 8SJ
    • Royal Hospital for Sick Children
  • London, United Kingdom, E1 1BB
    • Royal London Hospital
  • London, United Kingdom, WC1N 3JH
    • Great Ormond Street Hospital For Children NHS Foundation Trust
  • London, United Kingdom, SW10 9NH
    • Chelsea And Westminster Hospital NHS Foundation Trust
  • Sheffield, United Kingdom, S10 2TH
    • Sheffield Children Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama Pediatric Gastroenterology
    • Mobile, Alabama, United States, 36604
      • University of South Alabama Women's and Children's Hospital
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
    • Phoenix, Arizona, United States, 85008
      • Arizona Children's Center at Maricopa Medical Center
  • Arkansas
    • Fayetteville, Arkansas, United States, 72703
      • Northwest Arkansas Pediatric Clinic
    • Little Rock, Arkansas, United States, 72202
      • Arkansas Children's Hospital Research Institute
    • Little Rock, Arkansas, United States, 72212
      • Applied Clinical Research of Arkansas
  • California
    • Costa Mesa, California, United States, 92626
      • WCCT Global
    • Loma Linda, California, United States, 92350
      • Loma Linda University Health Care
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
  • Colorado
    • Colorado Springs, Colorado, United States, 80910
      • McB Clinical Research
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours/Alfred I. DuPont Hospital for Children
  • District of Columbia
    • Washington, District of Columbia, United States, 20020
      • Emmerson Clinical Research
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida
    • Hialeah, Florida, United States, 33016
      • Palmetto Professional Research
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic
    • Miami, Florida, United States, 33142
      • Acevedo Clinical Research Associates
    • Miami Lakes, Florida, United States, 33014
      • Savin Medical Group Research Center
    • Orlando, Florida, United States, 32819
      • Digestive & Liver Center of Florida
    • Pensacola, Florida, United States, 32504
      • Nemours Childrens Clinic
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Children's Center for Digestive Healthcare/GI Care for Kids
  • Illinois
    • Park Ridge, Illinois, United States, 60068
      • Center for Children's Digestive Health
    • Peoria, Illinois, United States, 61602
      • Methodist Medical Center
  • Indiana
    • Newburgh, Indiana, United States, 47630
      • PediaResearch, LLC - Newburgh
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • UnityPoint Health Des Moines/ Blank Children's Clinic
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Children's Hospital
  • Kansas
    • Wichita, Kansas, United States, 67205
      • Heartland Research Associates
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville Research Foundation Inc. Kosair Charities Pediatric Clinical Research Unit
    • Owensboro, Kentucky, United States, 42301
      • PediaResearch, LLC - Owensboro
  • Louisiana
    • New Orleans, Louisiana, United States, 70118
      • Children's Hospital
    • Shreveport, Louisiana, United States, 71101
      • Willis-Knighton Physician Network
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Children's Center
    • Silver Spring, Maryland, United States, 20910
      • Virgo-Carter Pediatrics
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • University of Mississippi Medical Center
    • Jackson, Mississippi, United States, 39202
      • Gastrointestinal Associates, PA
  • Missouri
    • Kansas City, Missouri, United States, 64145
      • The Children's Mercy Hospital
  • Nebraska
    • Bellevue, Nebraska, United States, 68005
      • Pioneer Clinical Research
    • Lincoln, Nebraska, United States, 68504
      • Midwest Children's Health Research Institute
  • New York
    • Buffalo, New York, United States, 14222
      • Digestive Diseases and Nutrition Center Women and Childrens Hospital of Buffalo
    • Jackson Heights, New York, United States, 11372
      • Smart Medical Research, Inc.
    • New York, New York, United States, 10032
      • Morgan Stanley Children's Hospital of New York Presbyterian
    • New York, New York, United States, 10021
      • NY Presbyterian Weill Cornell
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • UNC School of Medicine
  • Ohio
    • Beavercreek, Ohio, United States, 45431
      • PriMed Clinical Research
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital
    • Toledo, Ohio, United States, 43606
      • Toledo Children's Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Cyn3rgy Research
  • Pennsylvania
    • Erie, Pennsylvania, United States, 16506
      • Square-1 Clinical Research, Inc.
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Philadelphia, Pennsylvania, United States, 19134
      • St. Christopher's Hospital for Children/Drexel University
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh UPMC
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • AAPRI Clinical Research
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Coastal Clinical Research
    • Charleston, South Carolina, United States, 29412
      • Coastal Pediatric Associates - James Island
    • Greenville, South Carolina, United States, 29615
      • Greenville Health System
    • Mount Pleasant, South Carolina, United States, 29464
      • Coastal Pediatrics Associates - Mount Pleasant
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • The Jackson Clinic, P.C.
    • Memphis, Tennessee, United States, 38105
      • Le Bonheur Children's Hospital
    • Nashville, Tennessee, United States, 37232
      • Monroe Carell Junior Children's Hospital at Vanderbilt
  • Texas
    • Amarillo, Texas, United States, 79106
      • Texas Tech University Health Sciences Center
    • Austin, Texas, United States, 78756
      • Austin Center for Clinical Research
    • Baytown, Texas, United States, 77521
      • A1 Clinical Research
    • Corpus Christi, Texas, United States, 78413
      • 3rd Coast Research Associates
    • Dallas, Texas, United States, 75390
      • Childrens Medical Center Dallas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Laredo, Texas, United States, 78041
      • Envision Clinical Research, LLC
    • Longview, Texas, United States, 75605
      • DCOL Center for Clinical Research
    • Sealy, Texas, United States, 77474
      • Medical Clinics of Sealy
  • Utah
    • Logan, Utah, United States, 84341
      • Bridgerland Clinical Research
    • Salt Lake City, Utah, United States, 84132
      • Primary Children's Medical Center
    • Syracuse, Utah, United States, 84075
      • Wee Care Pediatrics
  • Vermont
    • Burlington, Vermont, United States, 05445
      • University of Vermont Medical Center
  • Virginia
    • Charlottesville, Virginia, United States, 22902
      • Pediatric Research of Charlottesville, LLC
    • Fairfax, Virginia, United States, 22031
      • INOVA Pediatric Digestive Diseases Center
    • Norfolk, Virginia, United States, 23507
      • The Children's Hospital of the King's Daughter
    • Roanoke, Virginia, United States, 24014
      • Pediatric Gastroenterology Carilion Medical Center
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinicial Research Center
    • Richland, Washington, United States, 99352
      • Zain Research LLC
    • Tacoma, Washington, United States, 98405
      • MultiCare Health System Institute for Research and Innovation
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 58226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Medically-confirmed diagnosis of Functional Constipation per Rome III Diagnostic Criteria for Childhood Functional Constipation
• At least 6 years of age but less than 18 years of age at the time of randomisation
• Only stable dose of selective serotonin re-uptake inhibitors (SSRIs), serotonin-specific reuptake inhibitor (SNRIs), or monoamine oxidase inhibitors (MAO) inhibitors are allowed if subject is taking antidepressants

Exclusion Criteria:

• Any gastrointestinal (GI) condition, other than constipation and/or irritable bowel syndrome (IBS), affecting GI motility or defecation
• Untreated faecal impaction at the time of screening
• Medical/surgical condition that might interfere with the absorption, distribution, metabolism, or excretion of the study medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lubiprostone; Participants receive lubiprostone twice daily (BID) up to 12 weeks	Drug: Lubiprostone; 12 or 24 mcg soft capsules of lubiprostone for oral administration, depending on baseline weight and response during week 1; Other Names: Amitiza
Placebo Comparator: Placebo; Participants receive placebo BID up to 12 weeks	Drug: Placebo; 0 mcg soft capsules of placebo for oral administration; Other Names: Matching Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Classified as Overall Responders at Week 12	An overall responder is defined as a participant who qualified as a weekly responder for 9 of the 12 treatment weeks, with durability demonstrated by at least 3 of the responder weeks occurring during the last 4 weeks of the treatment period. A weekly responder is defined as a participant who has at least 3 spontaneous bowel movements during the week, and at least one more than at baseline.	at Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Number of SBMs Observed Each Week for 12 Weeks	Data provided is based on observed cases. Baseline is the average of the 2 weeks before being randomized. Participants are summarized by actual dose received after week 1.	within 12 Weeks

Collaborators and Investigators

• Sponsor: Sucampo Pharma Americas, LLC
• Collaborators: Sucampo AG

Publications and helpful links

General Publications

• Benninga MA, Hussain SZ, Sood MR, Nurko S, Hyman P, Clifford RA, O'Gorman M, Losch-Beridon T, Mareya S, Lichtlen P, Di Lorenzo C. Lubiprostone for Pediatric Functional Constipation: Randomized, Controlled, Double-Blind Study With Long-term Extension. Clin Gastroenterol Hepatol. 2022 Mar;20(3):602-610.e5. doi: 10.1016/j.cgh.2021.04.005. Epub 2021 Apr 7.

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2013
• Primary Completion (Actual): July 27, 2016
• Study Completion (Actual): July 27, 2016

Study Registration Dates

• First Submitted: January 17, 2014
• First Submitted That Met QC Criteria: January 17, 2014
• First Posted (Estimate): January 22, 2014

Study Record Updates

• Last Update Posted (Actual): July 21, 2020
• Last Update Submitted That Met QC Criteria: July 20, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Constipation; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Lubiprostone
• Other Study ID Numbers: SAG/0211PFC-1131; 2013-004384-31 (EUDRACT_NUMBER); EMEA-000245-PIP01-08 (Other Identifier: EMEA Paediatric Investigational Plan)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Basic results are provided here, with statistical results and discussion reserved for publications.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No