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.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 439
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Health Sciences Center
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35242
      • The Birmingham Pain Center
    • Hueytown, Alabama, United States, 35023
      • Simon Williamson Clinic, PC
    • Mobile, Alabama, United States, 36608
      • Alabama Orthopedic Clinic
  • Arizona
    • Mesa, Arizona, United States, 85203
      • Clinical Research Advantage, Inc./ Mesa Family Medical Center
    • Tempe, Arizona, United States, 85282
      • Clinical Research Advantage, Inc.
    • Tucson, Arizona, United States, 85712
      • Quality of Life Medical & Research Center, LLC
    • Tucson, Arizona, United States, 85741
      • Genova Clinical Research, Inc.
    • Tucson, Arizona, United States, 85705
      • Harmony Clinical Research, Inc.
    • Tucson, Arizona, United States, 85710-3539
      • Verona Clinical Research, Inc.
    • Tucson, Arizona, United States, 85741
      • Pusch Ridge Family Medicine / WC Clinical Research
  • California
    • Anaheim, California, United States, 92801
      • Advanced Clinical Research Institute
    • Anaheim, California, United States, 92801
      • Orange County Clinical Trials, Inc.
    • Chula Vista, California, United States, 91910
      • Gregory J. Wiener, MD PC
    • Garden Grove, California, United States, 92840
      • Digestive and Liver Disease Specialists
    • Garden Grove, California, United States, 92843
      • RX Clinical Research, Inc
    • Laguna Hills, California, United States, 92653
      • Physicians Clinical Research Corporation
    • Loma Linda, California, United States, 92354
      • Loma Linda University Physicians Medical Group
    • Long Beach, California, United States, 90807
      • HealthCare Partners Medical Group
    • Los Angeles, California, United States, 90036
      • Impact Clinical Trials
    • Los Angeles, California, United States, 90095
      • The Regents of the University of California, Los Angeles
    • Pasadena, California, United States, 91105
      • Pasadena Rehabilitation Institute
    • Sacramento, California, United States, 95831
      • Northern California Research Corporation
    • Solana Beach, California, United States, 92075
      • SB Family Medicine
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Lynn Institute Of The Rockies
    • Pueblo, Colorado, United States, 81001
      • Lynn Institute of Pueblo
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Advanced Diagnostic Pain Treatment Center
    • Ridgefield, Connecticut, United States, 06877
      • International Research Clinicians of Conneticut
    • Trumbull, Connecticut, United States, 06611
      • New England Research Associates, LLC
  • Florida
    • Brooksville, Florida, United States, 34613
      • Meridien Research
    • Clermont, Florida, United States, 34711
      • South Lake Pain Institute
    • Daytona Beach, Florida, United States, 32117
      • International Medical Research
    • Daytona Beach, Florida, United States, 32117
      • Century Clinical Research
    • Fort Myers, Florida, United States, 33916
      • Clinical Physiology Associates/Clinical Study Center
    • Gainesville, Florida, United States, 32607
      • Southeaster Integrated Medical, PL d/b/a Florida Medical Research Institute
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach Research Center
  • Georgia
    • Dawsonville, Georgia, United States, 30534
      • North Georgia Premier Research
    • Decatur, Georgia, United States, 30034
      • Best Clinical Research
    • Marietta, Georgia, United States, 30060
      • Drug Studies America
    • Stockbridge, Georgia, United States, 30281
      • Pinnacle Trials Inc.
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Rosemark Women Care Specialists
    • Nampa, Idaho, United States, 83686
      • Saltzer Medical Group
  • Illinois
    • Bloomington, Illinois, United States, 61701
      • Millenium Pain Center
    • Chicago, Illinois, United States, 60612
      • University of Illinois Medical Center
    • Peoria, Illinois, United States, 61614
      • Redhead Research Inc., dba Research Associates of Central Illinois
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Integrated Clinical Trial Services, Inc.
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • The Pain Treatment Center of the Bluegrass and Ballard Wright, MD PSC
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Gulf Coast Research, LLC
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
    • Shreveport, Louisiana, United States, 71103
      • The Willis-Knighton Pain Management Center
  • Maryland
    • Bethesda, Maryland, United States, 20814
      • Pain and Rehabilitation Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • The Brigham and Women's Hospital
  • Michigan
    • Benzonia, Michigan, United States, 49616
      • Professional Clinical Research, Benzonia
    • Dearborn, Michigan, United States, 48124
      • Center for Clinical Studies
    • Flint, Michigan, United States, 48504
      • Apex Medical Research, AMR, Inc.
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • Digestive Health Specialists, PA
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Impact Clinical Trials, Las Vegas
    • Las Vegas, Nevada, United States, 89106
      • Office of Stephen H. Miller, MD
    • Reno, Nevada, United States, 89557
      • University of Nevada
  • New Jersey
    • Camden, New Jersey, United States, 08103
      • Cooper Health System
    • Stratford, New Jersey, United States, 08084
      • UMDNJ
    • Voorhees, New Jersey, United States, 08043
      • Partners in Primary Care
    • Watchung, New Jersey, United States, 07069
      • Abraham D. Morganoff, MD PA
  • New York
    • Fulton, New York, United States, 13069
      • Northway Medical Associates
    • Great Neck, New York, United States, 11021
      • Long Island Clinical Research Associates, LLP
    • Great Neck, New York, United States, 11023
      • Long Island Gastrointestinal Research Group
    • Rochester, New York, United States, 14642
      • University of Rochester
  • North Carolina
    • Durham, North Carolina, United States, 27704
      • Diversified Research
    • Greensboro, North Carolina, United States, 27408
      • Medoff Medical/ Vital re:Search
    • Statesville, North Carolina, United States, 28625
      • Carolina Pharmaceutical Research
    • Winston-Salem, North Carolina, United States, 27103
      • Center for Clinical Research, LLC
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • St. Alexius Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • COR Clinical Research, LLC
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Pain Research of Oregon, LLC
    • Portland, Oregon, United States, 97219
      • Affinity Research
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18104
      • Private Practice of Dr. Hasan
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center
    • Uniontown, Pennsylvania, United States, 15401
      • Preferred Primary Care Physicians
  • Rhode Island
    • Cumberland, Rhode Island, United States, 02864
      • Partners in Clinical Research
    • Providence, Rhode Island, United States, 02905
      • University Gastroenterology
  • South Carolina
    • North Charleston, South Carolina, United States, 29406
      • Trident Institute of Medical Research, LLC
  • Tennessee
    • Chattanooga, Tennessee, United States, 37403
      • Southeastern Clinical Research
    • Hendersonville, Tennessee, United States, 37075
      • Comprehensive Pain Specialists, PLLC
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University - Interventional Pain Center
    • Savannah, Tennessee, United States, 38372
      • Integrity Clinical Research, LLC
  • Texas
    • Dallas, Texas, United States, 75216
      • Dallas VA Research Corporation, Inc.
    • Dallas, Texas, United States, 75234
      • Bexar Clinical Trials, LLC
    • Odessa, Texas, United States, 79761
      • Permian Research Foundation
    • Richardson, Texas, United States, 75082
      • Bexar Clinical Trials, LLC
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Salt Lake Research, PLLC
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Digestive and Liver Disease Specialists
    • Richmond, Virginia, United States, 23298
      • General Clinical Research Center, Virginia Commonwealth University, North Hospital
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53295
      • Clement J. Zablocki VA Medical Center
    • Milwaukee, Wisconsin, United States, 53221
      • Metro Physicians a Division of Wheaton Franciscan Medical Group

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 (OBD) 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 inhibitor (SSRIs), Serotonin-norepinephrine reuptake inhibitor (SNRIs), or Monoamine oxidase inhibitor (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:

• 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).
• Opioid dose adjustment (+/- 30%), and/or change in opioid agent or route of administration within 30 days of screening.
• Gastrointestinal or abdominal surgical procedures within 90 days prior to screening.
• Non-ambulatory patients, or those who are unable to eat/drink, take oral medications, or to hold down oral medications due to vomiting.
• 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.
• Prior use of Amitiza, lubiprostone, SPI-0211, or RU-0211.

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	Measure Description	Time Frame
Mean Weekly Spontaneous Bowel Movements at Week 8	Spontaneous bowel movements (SBMs) are defined as bowel movements without the aid of drugs.	at Week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Number of Spontaneous Bowel Movements (SBM) Per Week Within 12 Weeks	Average weekly SBM frequency was calculated from data collected from Week 1 through Week 12	within 12 weeks
Number of Participants With the First Post-dose Spontaneous Bowel Movement Within 48 Hours Post-dose	The number of participants who experienced their first post-dose Spontaneous Bowel Movement within 24 and 48 hours after dosing started.	within 48 hours post-dose
Number of Participants Classified as Responders	Number of participants who remained on treatment for at least 8 weeks, and reported at least 3 SBMs for at least half the weeks on study.	within 12 weeks
Mean Change From Baseline in Straining, Stool Consistency, Constipation Severity, Abdominal Bloating, Abdominal Discomfort, and Bowel Habit Regularity	Measures collected over 12-week treatment period were averaged, and the score at baseline was subtracted from the score at week 12 to determine the change from baseline. Straining scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe - higher scores are worse; Stool consistency scale: 0 = very loose, 1 = loose, 2 = normal, 3 = hard, 4 = very hard (little balls) - middle scores are best; Constipation severity scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe - higher scores are worse; Abdominal bloating scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe - higher scores are worse; Abdominal discomfort scale: 0 = absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe - higher scores are worse; Bowel habit regularity scale: 7-point scale, where 1 = very regular and 7 = very irregular - higher scores are worse	within 12 weeks
Participant Reported Outcome of Treatment Effectiveness	Participants rated treatment effectiveness at the end of each treatment week during the study on a 5-point scale, where 0 = not at all effective, 1 = a little bit effective, 2 = moderately effective, 3 = quite a bit effective, 4 = extremely effective. The 12 weekly scores were averaged. Higher scores mean the drug was more effective.	within 12 weeks

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Cryer B, Katz S, Vallejo R, Popescu A, Ueno R. A randomized study of lubiprostone for opioid-induced constipation in patients with chronic noncancer pain. Pain Med. 2014 Nov;15(11):1825-34. doi: 10.1111/pme.12437. Epub 2014 Apr 9.

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 4, 2008
• First Submitted That Met QC Criteria: January 15, 2008
• First Posted (Estimate): January 16, 2008

Study Record Updates

• Last Update Posted (Actual): December 16, 2019
• Last Update Submitted That Met QC Criteria: December 6, 2019
• Last Verified: December 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: OBD0631

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO