A Comparison of the Effects of ORP-101 Versus Placebo in Adult Patients With Irritable Bowel Syndrome With Diarrhea (IBS-D)

A Double-Blind, Placebo-Controlled, Phase 2, Responsive Adaptive Randomization Study of ORP-101 in Patients With Irritable Bowel Syndrome With Diarrhea (IBS-D)

This study will evaluate the effects of ORP-101 versus placebo on stool consistency and abdominal pain in patients with Irritable Bowel Syndrome with Diarrhea (IBS-D). It will also assess the safety and tolerability of ORP-101 in patients with IBS-D.

Study Overview

• Status: Completed
• Conditions: Irritable Bowel Syndrome With Diarrhea
• Intervention / Treatment: Drug: Placebo; Drug: ORP-101

Detailed Description

The objectives of this study are to evaluate the efficacy, safety and tolerability of ORP-101 in patients with IBS-D. This is a randomized, double-blind, placebo-controlled, 3-arm, 12-week, parallel proof-of-concept study with 2 active arms (50 mg and 100 mg ORP-101, QD) and 1 matching placebo arm, using a responsive adaptive randomization approach. After screening, patients who qualify will enter the baseline symptom assessment period, during which they will be instructed on completion of an electronic diary for daily collection of data related to their IBS symptoms, bowel function and loperamide rescue usage (not allowed during baseline).

Patients who meet all entry criteria will be randomized to receive one of two different doses of ORP-101 tablets or placebo for 12 weeks. The study drug will be taken once daily, approximately 30 minutes prior to breakfast. Patients will return to the clinic on Days 14, 28, 56, 84 (12 weeks) and 2 weeks after dosing has completed (Day 98) for a follow-up visit.

Study subjects will include both male and female adults. Approximately 320 patients with IBS-D will be randomized to receive study drug or placebo. Randomization will be stratified by history of cholecystectomy/gallbladder agenesis.

• Study Type: Interventional
• Enrollment (Actual): 321
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research (Site 155)
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Synexus Clinical Research US, Inc. - Phoenix Southeast (Site 123)
    • Phoenix, Arizona, United States, 85018
      • Elite Clinical Studies - Phoenix (Site 116)
    • Tucson, Arizona, United States, 85712
      • Del Sol Research Management - BTC (Site 165)
    • Tucson, Arizona, United States, 85741
      • Synexus Clinical Research US, Inc. - Orange Grove Family Practice (Site 118)
    • Tucson, Arizona, United States, 85745
      • Del Sol Research Management - BTC (Site 130)
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Preferred Research Partners - ClinEdge (Site 103)
    • Little Rock, Arkansas, United States, 72212
      • Applied Research Center (Site 158)
  • Connecticut
    • Bristol, Connecticut, United States, 06010
      • Connecticut Clinical Research Foundation (Site 136)
  • Florida
    • Boynton Beach, Florida, United States, 33435
      • Imagine Research of Palm Beach County (Site 187)
    • Lakeland, Florida, United States, 33803
      • Meridien Research - Lakeland (Site 167)
    • Lauderdale Lakes, Florida, United States, 33319
      • Precision Clinical Research LLC (Site 139)
    • Maitland, Florida, United States, 32751
      • Meridien Research, Maitland - Inpatient (Site 141)
    • Oviedo, Florida, United States, 32765
      • Oviedo Medical Research (Site 140)
    • Pompano Beach, Florida, United States, 33060
      • Clinical Research Center of Florida (Site 186)
    • Saint Petersburg, Florida, United States, 33709
      • Meridien Research - St. Petersburg (Site 132)
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Agile Clinical Research Trials, LLC (Site 163)
    • Columbus, Georgia, United States, 31904
      • Gastrointestinal Diseases, Inc. Research (Site 137)
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research (Site 169)
    • Suwanee, Georgia, United States, 30024
      • In Quest Medical Research, LLC (Site 131)
    • Valdosta, Georgia, United States, 31605
      • GNP Research (Site 145)
  • Idaho
    • Boise, Idaho, United States, 83704
      • Northwest Clinical Trials - ClinEdge (Site 133)
  • Illinois
    • Chicago, Illinois, United States, 60602
      • Synexus Clinical Research US, Inc. - Chicago (Site 120)
  • Indiana
    • Brownsburg, Indiana, United States, 46112
      • Investigators Research Group, LLC (Site 188)
    • Evansville, Indiana, United States, 47714
      • Synexus Clinical Research US, Inc. - Allaw (Site 102)
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Alliance for Multispecialty Research, LLC (Site 159)
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center (Site 115)
  • Minnesota
    • Richfield, Minnesota, United States, 55423
      • AES-DRS-Synexus Clinical Research US, Inc.-Minneapolis (site 114)
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Sundance Clinical Research (Site 175)
  • Nebraska
    • Omaha, Nebraska, United States, 68144
      • Synexus Clinical Research US, Inc. - Omaha (Site 113)
    • Papillion, Nebraska, United States, 68046
      • Synexus Clinical Research US, Inc. - McGill Family Practice, P.C. (Site 126)
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Jubilee Clinical Research - BTC (Site 162)
    • Las Vegas, Nevada, United States, 89106
      • Sierra Clinical Research (Site 179)
  • New Mexico
    • Albuquerque, New Mexico, United States, 87108
      • Lovelace Scientific Resources Inc. (Site 176)
  • New York
    • Brooklyn, New York, United States, 11235
      • NY Scientific (Site 153)
    • Great Neck, New York, United States, 11023
      • Long Island Gastrointestinal Research Group LLP (Site 107)
    • Jamaica, New York, United States, 11432
      • Synexus Clinical Research US, Inc. - Queens (Site 119)
    • Newburgh, New York, United States, 12553
      • Mid Hudson Medical Research PLLC (Site 174)
    • Williamsville, New York, United States, 14221
      • Upstate Clinical Research Associates LLC - ClinEdge (Site 164)
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • OnSite Clinical Solutions, LLC - ClinEdge (Site 147)
    • Charlotte, North Carolina, United States, 28277
      • OnSite Clinical Solutions, LLC - ClinEdge (Site 146)
    • High Point, North Carolina, United States, 27262
      • Peters Medical Research, LLC - ClinEdge (SIte 111)
    • Salisbury, North Carolina, United States, 28144
      • PMG Research of Salisbury LLC (Site 110)
    • Wilmington, North Carolina, United States, 28401
      • PMG Research of Wilmington (Site 185)
    • Winston-Salem, North Carolina, United States, 27103
      • PMG Research of Winston-Salem (Site 124)
  • Ohio
    • Akron, Ohio, United States, 44311
      • Synexus Clinical Research US, Inc. - Akron (Site 122)
    • Cincinnati, Ohio, United States, 45215
      • Hometown Urgent Care and Research (Site 150)
    • Cincinnati, Ohio, United States, 45236
      • Synexus Clinical Research US, Inc. - Cincinnati (Site 127)
    • Columbus, Ohio, United States, 43212
      • Synexus Clinical Research US, Inc. - Columbus (Site 108)
    • Columbus, Ohio, United States, 43214
      • Hometown Urgent Care and Research (Site 149)
    • Columbus, Ohio, United States, 43215
      • Remington Davis Inc (Site 144)
    • Dayton, Ohio, United States, 45419
      • PriMed Clinical Research - ClinEdge (Site 121)
    • Dayton, Ohio, United States, 45424
      • Hometown Urgent Care and Research (Site 151)
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73109
      • Medical Research international (Site 180)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19114
      • Tristar Clinical Investigations, P.C. (Site 168)
    • Uniontown, Pennsylvania, United States, 15401
      • Frontier Clinical Research, LLC (Site 171)
  • South Carolina
    • Fort Mill, South Carolina, United States, 29707
      • Piedmont Research Partners LLC - BTC (Site 157)
    • Greer, South Carolina, United States, 29651
      • Synexus clinical Research US, Inc. - Greer (Site 105)
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • WR-ClinSearch, LLC (Site 129)
    • Jackson, Tennessee, United States, 38305
      • The Jackson Clinic PA - ClinEdge (Site 135)
    • Knoxville, Tennessee, United States, 37909
      • New Phase Research & Development (Site 181)
  • Texas
    • Austin, Texas, United States, 78704
      • Benchmark Research - Austin (Site 178)
    • Georgetown, Texas, United States, 78628
      • Advanced Medical Trials (SIte 142)
    • Houston, Texas, United States, 77099
      • Pioneer Research Solutions (Site 125)
    • Missouri City, Texas, United States, 77459
      • Synergy Group US, LLC - Missouri City - Hunt (Site 156)
    • Pearland, Texas, United States, 77584
      • DM Clinical Research - LinQ Research - ERN (Site 109)
    • San Antonio, Texas, United States, 48229
      • Synexus Clinical Research US, Inc. - San Antonio (Site 112)
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas Incorporated - ClinEdge (Site 134)
  • Utah
    • Murray, Utah, United States, 84123
      • Synexus Clinical Research US, Inc. - Salt Lake City (Site 101)
    • Ogden, Utah, United States, 84405
      • Advanced Research Institute (Site 117)
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads Inc. (Site 173)
    • Petersburg, Virginia, United States, 23805
      • The Center of Gastrointestinal Health (Site 152)
  • Washington
    • Bellevue, Washington, United States, 98007
      • Northwest Clinical Research Center - ClinEdge (Site 148)
  • West Virginia
    • Morgantown, West Virginia, United States, 26505
      • Exemplar Research, Inc. - Morgantown (Site 172)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willing and able to comply with protocol, including completion of electronic daily diary as required.
• Has a diagnosis of IBS-D (Irritable Bowel Syndrome with Diarrhea) and meets the Rome IV Criteria, by history, for both IBS and IBS-D.
• Has abdominal pain intensity score, and stool consistency as determined by protocol and assessed by Investigator for the week prior to randomization.
• Has not used loperamide within the 14 days prior to randomization.
• Is on a stable diet for the past 12 weeks and is not planning to change lifestyle and/or diet during study.

Exclusion Criteria:

• History of clinically relevant pancreatic conditions including pancreatitis, pancreas divisum, or Sphincter of Oddi (SO) dysfunction with pancreatic manifestations.
• History of biliary pathology including acute cholecystitis within 6 months or biliary pain including post-cholecystectomy pain.
• Patients who have had biliary sphincterotomy with post-procedure persistent abnormal liver function transaminases (LFTs).
• Planned elective surgery within the next 4 months.
• Significant and/or severe medical illnesses such as cardiovascular, neurological, infectious, renal, hepatic or respiratory disorders that would interfere with the patient's medical care, participation in, or conduct of the study.
• History of intestinal obstruction, stricture, toxic megacolon, GI (gastro-intestinal) perforation, fecal impaction, gastric banding, bariatric surgery, adhesions, ischemic colitis, or impaired intestinal circulation (e.g. aorto-iliac disease).
• History of lactose intolerance uncontrolled on a lactose-free diet, or other malabsorption syndromes (e.g. fructose malabsorption).
• Dysphagia or difficulty swallowing pills.
• History of inflammatory bowel disease, celiac disease, Clostridium difficile colitis or have had recent unexplained GI bleeding within 3 months prior to screening.
• History of major gastric, hepatic, pancreatic or intestinal surgery (appendectomy, hemorrhoidectomy, or polypectomy allowed as long as occurred > 3 months prior to trial screening; uncomplicated laparoscopic or open cholecystectomy is allowed if no history of post-operative biliary tract pain and surgery occurred > 3 months prior to screening).
• Patients >40 years of age at high risk for colon cancer must have had a screening colonoscopy within the past 3 years prior to trial screening visit or > 50 years of age, must have had a normal screening colonoscopy within the past 10 years prior to trial screening visit. Patients with Lynch Syndrome or Familial Polyposis are excluded from the study.

Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo, once daily	Drug: Placebo; Oral tablet
Experimental: ORP-101 50 mg; ORP-101 (50 mg) once daily	Drug: ORP-101; Oral tablet; Other Names: dibuprenorphine-ethyl-ether
Experimental: ORP-101 100 mg; ORP-101 (100 mg), once daily	Drug: ORP-101; Oral tablet; Other Names: dibuprenorphine-ethyl-ether

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Are Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain and Daily Stool Consistency Scores	Composite responders are defined as participants who met the daily response criteria for at least 50% of the days with diary entries over the 12-week interval. A participant must meet both of the following criteria on a given day to be a daily responder: 1) Daily pain response: worst abdominal pain scores in the past 24 hours improved by ≥30% compared to baseline (average of daily worst abdominal pain the week prior to randomization). 2) Average of daily stool consistency response for all reported bowel movements on the specific day: Bristol Stool Scale (BSS) score <5 (ie, score of 1, 2, 3, or 4) or the absence of a bowel movement if accompanied by ≥30% improvement in worst abdominal pain compared to baseline pain.	Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Are Responders in Daily Worst Abdominal Pain Scores	Pain responders over the interval from Weeks 1-12 are defined as those patients who meet the daily pain response criteria for at least 50% of days with diary entry during the interval. To be eligible to be a responder, a patient must have a minimum of 60 days of diary entries over the 12-week interval.	Week 12
Percentage of Participants Who Are Responders in Daily Stool Consistency Scores	Stool consistency responders over the interval from Weeks 1-12 are defined as those patients who meet the daily stool consistency response criteria for at least 50% of days with diary entry during the interval. To be eligible to be a responder, a patient must have a minimum of 60 days of diary entries over the 12-week interval.	Baseline to Week 12
Percentage of Participants Who are Responders in IBS Global Symptom Scores	IBS Global Symptom Score: Change from baseline for interval from Weeks 1-12: A responder is defined as a patient who has an IBS global symptom score of 0 (none) or 1 (mild) or daily IBS symptom score improved by ≥ 2.0 compared to the average in the week prior to randomization. A minimum of 60 days of diary entries over the 12-week interval is required for responders.	Week 12
Percentage of Participants Who are Responders in IBS Adequate Relief Scores	IBS Adequate Relief: Percent of responders over the interval from Weeks 1-12. Responders are defined as those patients with a weekly response of "Yes" to adequate relief of their IBS symptoms for at least 50% of the total weeks during the interval.	Week 12
Percentage of Participants Who Are Modified Composite Responders Based on Responder Endpoints	A modified composite responder endpoint in which a daily responder will be defined as having both: 1) Pain response: worst abdominal pain score in the past 24 hours improved ≥ 30% compared to the average in the week prior to randomization. 2) Stool consistency response: all bowel movements on the specific day must have BSFS score < 5 or the absence of a bowel movement if accompanied by ≥ 30% improvement in worst abdominal pain.	Week 12
Change from Baseline in Daily Abdominal Discomfort Scores	Discomfort: Change from baseline in daily abdominal discomfort scores	Week 12
Change from Baseline in Daily Abdominal Bloating Scores	Bloating: Change from baseline in daily abdominal bloating scores	Week 12
Number of Bowel Movements Per Day	Frequency: Change from baseline in mean number of bowel movements per day	Week 12
Number of Bowel Incontinence Free Days	Change from baseline in mean number of bowel incontinence episodes per day as well as the number of incontinence-free days	Week 12

Collaborators and Investigators

• Sponsor: OrphoMed, Inc.
• Collaborators: PPD

Publications and helpful links

Helpful Links

• FDA Safety Alerts and Recalls
• For potential patients/subjects, if interested in the study, please visit this website and complete the survey

Study record dates

Study Major Dates

• Study Start (Actual): November 22, 2019
• Primary Completion (Actual): October 4, 2021
• Study Completion (Actual): October 4, 2021

Study Registration Dates

• First Submitted: October 15, 2019
• First Submitted That Met QC Criteria: October 15, 2019
• First Posted (Actual): October 17, 2019

Study Record Updates

• Last Update Posted (Actual): March 4, 2022
• Last Update Submitted That Met QC Criteria: March 3, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Irritable Bowel Syndrome; IBS
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Disease; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Colonic Diseases, Functional; Colonic Diseases; Intestinal Diseases; Syndrome; Irritable Bowel Syndrome; Diarrhea; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Anesthetics, Inhalation; Ether
• Other Study ID Numbers: OM-201

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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