Opioid-induced Bowel Dysfunction Pivotal Assessment of Lubiprostone (OPAL)

A Multi-center, Randomized, Double-Blinded Study of the Efficacy and Safety of Lubiprostone in Patients With Opioid-induced Bowel Dysfunction (OBD)

The primary purpose of this study is to evaluate the efficacy and safety of lubiprostone administration in patients with opioid-induced bowel dysfunction (OBD).

Study Overview

• Status: Completed
• Conditions: Opioid-Induced Bowel Dysfunction
• Intervention / Treatment: Drug: Placebo; Drug: Lubiprostone

• Study Type: Interventional
• Enrollment (Actual): 437
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T5A 4L8
      • Hermitage Medicentre
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Health Sciences Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare Hamilton
    • London, Ontario, Canada, N5X4E7
      • Pharmaceutical Integrated Research Company
    • Richmond Hill, Ontario, Canada, L4B 3P8
      • DHC Research
• United States
  • Alabama
    • Tuscaloosa, Alabama, United States, 35404
      • Tuscaloosa VA Medical Center
  • Arizona
    • Phoenix, Arizona, United States, 85029
      • Redpoint Research
    • Phoenix, Arizona, United States, 85050
      • HOPE Research Institute, LLC
    • Phoenix, Arizona, United States, 85012
      • Carl T Hayden VA Medical Center
    • Tempe, Arizona, United States, 85222
      • Clinical Research Advantage, Inc. / East Valley Family Physicians, PLC
    • Tempe, Arizona, United States, 85282
      • Premiere Pharamaceutical Research, LLC
    • Tucson, Arizona, United States, 85705
      • Harmony Clinical Research, Inc.
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Martin Bowen Hefley Knee
  • California
    • Arcadia, California, United States, 91007
      • Advanced Pain Institute
    • Bakersfield, California, United States, 93311
      • Pain Institute of CA
    • Chino, California, United States, 91710
      • Catalina Research Institute, LLC
    • Huntington Beach, California, United States, 92647
      • California Pain Center
    • Laguna Hills, California, United States, 92637
      • Shreenath Clinical Service
    • Loma Linda, California, United States, 92354
      • Loma Linda University Physicians Medical Group
    • Long Beach, California, United States, 90822-5201
      • VA Long Beach Healthcare System
    • San Francisco, California, United States, 94117
      • Rider Research Group
  • Colorado
    • Colorado Springs, Colorado, United States, 80904
      • Clinicos, LLC
    • Lakewood, Colorado, United States, 80215
      • Rocky Mountain Gastroenterology Associates
    • Littleton, Colorado, United States, 80120
      • Arapahoe Gastroenterology, PC
    • Littleton, Colorado, United States, 80122
      • Metro Clinical Research, LLC
  • Florida
    • Boca Raton, Florida, United States, 33486
      • Clinical Trial Management of Boca Raton, Inc.
    • Jacksonville, Florida, United States, 32257
      • Florida Institute of Medical Research
    • Jupiter, Florida, United States, 33458
      • Drug Study Institute
    • Naples, Florida, United States, 34102
      • Gastroenterology Group Of Naples
    • Niceville, Florida, United States, 32578
      • Kenneth W. Ponder, MD PA
    • North Miami, Florida, United States, 33161
      • North Miami Research, Inc.
    • Ocala, Florida, United States, 34471
      • Renstar Inc.
    • Ormond Beach, Florida, United States, 32174
      • Peninsula Research, Inc
    • Pinellas Park, Florida, United States, 33782
      • DMI Research, Inc.
    • Plantation, Florida, United States, 33324
      • Sunrise Medical Research, Inc.
    • Port Orange, Florida, United States, 32129
      • Accord Clinical Research, LLC
    • Saint Petersburg, Florida, United States, 33709
      • Meridien Research
    • Sarasota, Florida, United States, 34233
      • Lovelace Scientific Resources, Inc.
    • Tampa, Florida, United States, 33613
      • Stedman Clinical Trials
    • Tampa, Florida, United States, 33603
      • Clinical Research of West Florida, Inc.
  • Georgia
    • Augusta, Georgia, United States, 30901
      • Advanced Pain Management
    • Calhoun, Georgia, United States, 30701
      • Global Research Partners & Consultants, Incs.
    • Decatur, Georgia, United States, 30035
      • Q Clinical Research
  • Illinois
    • Chicago, Illinois, United States, 60616
      • Apex Medical Research, AMR, Inc.
    • Chicago, Illinois, United States, 60617
      • Claude Mandel Medical Center
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Medisphere Medical Research Center
    • Evansville, Indiana, United States, 47630
      • Advanced Pain Care Clinic
    • Indianapolis, Indiana, United States, 46260
      • Davis Clinic, PC
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Louisiana
    • Lafayette, Louisiana, United States, 70503
      • Gulf Coast Research, LLC
    • Monroe, Louisiana, United States, 71201
      • Delta Research Partners, LLC
    • Shreveport, Louisiana, United States, 71103
      • Louisiana Research Center, LLC
  • Maryland
    • Baltimore, Maryland, United States, 21228
      • Rehabilitation Team West, PA
    • Columbia, Maryland, United States, 21045
      • Columbia Medical Practice/ RxTrials, Inc.
    • Hagerstown, Maryland, United States, 21742
      • Washington County Hospital Association - The Center for Clinical Research
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center, Harvard Medical School
    • Wellesley Hills, Massachusetts, United States, 02481
      • MedVadis Research Corporation
  • Michigan
    • Chesterfield, Michigan, United States, 48047
      • Clinical Research Institute of Michigan, LLC
    • Interlochen, Michigan, United States, 49643
      • Professional Clinical Research, Inc.
    • Lansing, Michigan, United States, 48917
      • PCM Medical Services
    • Paw Paw, Michigan, United States, 49079
      • Women's Health Care Specialists, PC
    • Traverse City, Michigan, United States, 49684
      • Medical Research Associates
    • Troy, Michigan, United States, 48098
      • Center for Digestive Health
  • Minnesota
    • Edina, Minnesota, United States, 55435
      • MAPS Applied Research Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Mississippi
    • Flowood, Mississippi, United States, 39232
      • Precise Research, Inc.
  • Missouri
    • Saint Louis, Missouri, United States, 63117
      • Medex Healthcare Research
  • Montana
    • Missoula, Montana, United States, 59802
      • Montana Neuroscience Institute Foundation / Montana Spine and Pain Center
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Creighton University Medical Center
  • Nevada
    • Las Vegas, Nevada, United States, 89123
      • Advanced Biomedical Research of America
    • Las Vegas, Nevada, United States, 89146
      • Lovelace Scientific Resources, Inc.
  • New Jersey
    • Cedar Knolls, New Jersey, United States, 07927
      • Gastroenterology Research Associates
    • Elizabeth, New Jersey, United States, 07202
      • Central Jersey Medical Research Center
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Hospital, Institute for Clinical Research
    • Voorhees, New Jersey, United States, 08043
      • Advanced Pain Consultants
  • New York
    • New York, New York, United States, 10022
      • Research Across America
    • New York, New York, United States, 10004
      • Medex Healthcare Research, Inc.
    • New York, New York, United States, 10016
      • New York University Pain Management Center
    • Valley Stream, New York, United States, 11580
      • North American Partners
    • Williamsville, New York, United States, 14221
      • Upstate Clinical Research Associates
  • North Carolina
    • Asheboro, North Carolina, United States, 27203
      • Randolph Medical Associates
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Greenville, North Carolina, United States, 27834
      • Carolina Research
    • Harrisburg, North Carolina, United States, 28075
      • Carolina Digestive Health Associates
    • High Point, North Carolina, United States, 27262
      • Peters Medical Research, LLC
    • Lexington, North Carolina, United States, 27295
      • Triangle Medical Research
    • New Bern, North Carolina, United States, 28562
      • Southern Gastroenterology Associates
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Valley Medical Primary Care
    • Cincinnati, Ohio, United States, 45238
      • Glenway Family Medicine
    • Columbus, Ohio, United States, 43210-1228
      • The Ohio State University Medical Center
    • Dayton, Ohio, United States, 45432
      • Urgent Care Specialists
    • Marion, Ohio, United States, 43302
      • RAS Health Ltd.
    • Toledo, Ohio, United States, 43614
      • University of Toledo - Health Science Campus
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
    • Oklahoma City, Oklahoma, United States, 73134
      • Memorial Clinical Research
    • Oklahoma City, Oklahoma, United States, 73112
      • Paradigm Research Professionals, LLP
  • Oregon
    • Medford, Oregon, United States, 97504
      • Medford Medical Clinic, LLP
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital - Neurosciences and Pain Research
    • Philadelphia, Pennsylvania, United States, 19414
      • Einstein Pain Institute
    • Yardley, Pennsylvania, United States, 19067
      • Jeffry A. Lindenbaum DO, PC
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • Baptist Medical Tower Suite 740
    • Milan, Tennessee, United States, 38358
      • Integrity Clinical Research, LLC
  • Texas
    • Hurst, Texas, United States, 76054
      • Texas Familicare Clinical Research
    • Longview, Texas, United States, 75605
      • DCOL Center for Clinical Research
    • Richardson, Texas, United States, 75082
      • Bexar Clinical Trials, LLC
  • Utah
    • Ogden, Utah, United States, 84405
      • Advance Research Institute
    • Salt Lake City, Utah, United States, 84124
      • Highland Clinical Research
    • Salt Lake City, Utah, United States, 84132-2410
      • University of Utah
  • Virginia
    • Christiansburg, Virginia, United States, 24073
      • New River Valley Research Institute
    • Portsmouth, Virginia, United States, 23707
      • Hampton Roads Institute for Performance and Sports Medicine (HIPS)
    • Richmond, Virginia, United States, 23249
      • McGuire Research Institute
  • Washington
    • Bellevue, Washington, United States, 98004
      • Northwest Gastroenterology Associates
    • Spokane, Washington, United States, 99204
      • Daniel R. Coulston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Consistent treatment for chronic, non-cancer-related pain with any full agonist opioid for at least 30 days prior to screening.
• Diagnosis of opioid-induced bowel dysfunction as confirmed during the screening period.
• If patient has a history of chronic constipation, condition must have been exacerbated by initiation of opioid treatment.
• Use of prescribed or over-the-counter (OTC) medication that affects gastrointestinal motility (other than opioid therapy) must be discontinued during the study.
• If treated for clinical depression with selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or monoamine oxidase (MAO) inhibitors, treatment must have been at a stable dose for at least 30 days prior to screening.
• Use of laxative and stool softeners (with the exception of approved rescue medications) must be discontinued while on study.

Exclusion Criteria:

• Opioid dose adjustment (+/- 30%), and/or change in opioid agent or route of administration within 30 days of screening.
• Non-ambulatory patients, or those who are unable to eat/drink, take oral medications, or to hold down oral medications due to vomiting.
• Treatment with opioid therapy for cancer-related pain, abdominal pain, scleroderma, and/or for the management of drug addiction.
• Patient has been treated for cancer in the past 5 years (with the exception of localized basal cell, squamous cell skin cancer, or in situ cancer that has been resected).
• Gastrointestinal or abdominal surgical procedures within 90 days prior to screening.
• Female patients of childbearing potential who are unable/unwilling to use protocol-specified method(s) of birth control and/or are pregnant, nursing, or plan to become pregnant or nurse during the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lubiprostone; 24 mcg capsules twice daily (BID)	Drug: Lubiprostone; 24 mcg capsules twice daily (BID); Other Names: Amitiza®
Placebo Comparator: Placebo; 0 mcg capsules twice daily (BID)	Drug: Placebo; 0 mcg capsules twice daily (BID); Other Names: No other names

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change From Baseline in Mean Weekly Spontaneous Bowel Movement (SBM) Frequency in Subjects Without Dose Reduction Prior to Week 8	Baseline and Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Mean Weekly SBM Frequency	For overall assessment of change, average weekly rating was calculated from data collected from Week 1 through Week 12.	Baseline, Week 12, and Weeks 1-12
First Post-dose SBM	The number of participants that experienced first post-dose SBM 24 and 48 hour of dose initiation.	24 and 48 hours post-dose
Responder Rate	Number of participants, who remained on treatment for at least 8 weeks, and reported response (>=3 SBMs) for at least 50% of weeks on study.	Up to 12 weeks
Mean Changes From Baseline in Straining, Stool Consistency, Constipation Severity, Abdominal Bloating, Abdominal Discomfort, and Bowel Habit Regularity	Ratings over 12-week treatment period were averaged and difference from baseline score calculated Straining scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe Stool consistency scale: 0 = very loose, 1 = loose, 2 = normal, 3 = hard, 4 = very hard (little balls) Constipation severity scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe Abdominal bloating scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe Abdominal discomfort scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe Bowel habit regularity scale: 7-point scale, where 1 = very regular and 7 = very irregular	Weeks 1-12
Treatment Effectiveness	Treatment effectiveness scale: 0 = not at all effective, 1 = a little bit effective, 2 = moderately effective, 3 = quite a bit effective, 4 = extremely effective	Weeks 1-12

Collaborators and Investigators

• Sponsor: Sucampo Pharma Americas, LLC
• Collaborators: Sucampo Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): March 1, 2009

Study Registration Dates

• First Submitted: January 9, 2008
• First Submitted That Met QC Criteria: January 17, 2008
• First Posted (Estimate): January 18, 2008

Study Record Updates

• Last Update Posted (Actual): December 10, 2019
• Last Update Submitted That Met QC Criteria: December 6, 2019
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Digestive System Diseases; Substance-Related Disorders; Signs and Symptoms, Digestive; Narcotic-Related Disorders; Constipation; Gastrointestinal Diseases; Intestinal Diseases; Opioid-Induced Constipation; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Chloride Channel Agonists; Lubiprostone
• Other Study ID Numbers: OBD0632