Clinical trial NCT04129619: A Comparison of the Effects of ORP-101 Versus Placebo in Adult Patients With Irritable Bowel Syndrome With Diarrhea (IBS-D)
Official title: A Double-Blind, Placebo-Controlled, Phase 2, Responsive Adaptive Randomization Study of ORP-101 in Patients With Irritable Bowel Syndrome With Diarrhea (IBS-D)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Irritable Bowel Syndrome With Diarrhea
Keywords: Irritable Bowel Syndrome
IBS
Lead sponsor: OrphoMed, Inc.
Sponsor class: INDUSTRY
Collaborators: name: PPD Development, LP
First posted: 2019-10-17
Enrollment: 321
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Are Composite Responders Based on Improvements From Baseline in Daily Worst Abdominal Pain and Daily Stool Consistency Scores
timeFrame: Week 12
Secondary outcomes:
measure: Percentage of Participants Who Are Responders in Daily Worst Abdominal Pain Scores
timeFrame: Week 12
measure: Percentage of Participants Who Are Responders in Daily Stool Consistency Scores
timeFrame: Baseline to Week 12
measure: Percentage of Participants Who are Responders in IBS Global Symptom Scores
timeFrame: Week 12
measure: Percentage of Participants Who are Responders in IBS Adequate Relief Scores
timeFrame: Week 12
measure: Percentage of Participants Who Are Modified Composite Responders Based on Responder Endpoints
timeFrame: Week 12
measure: Change from Baseline in Daily Abdominal Discomfort Scores
timeFrame: Week 12
measure: Change from Baseline in Daily Abdominal Bloating Scores
timeFrame: Week 12
measure: Number of Bowel Movements Per Day
timeFrame: Week 12
measure: Number of Bowel Incontinence Free Days
timeFrame: Week 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Achieve Clinical Research (Site 155)
state: Alabama
city: Chandler
country: United States
facility: Synexus Clinical Research US, Inc. - Phoenix Southeast (Site 123)
state: Arizona
city: Phoenix
country: United States
facility: Elite Clinical Studies - Phoenix (Site 116)
state: Arizona
city: Tucson
country: United States
facility: Del Sol Research Management - BTC (Site 165)
state: Arizona
city: Tucson
country: United States
facility: Synexus Clinical Research US, Inc. - Orange Grove Family Practice (Site 118)
state: Arizona
city: Tucson
country: United States
facility: Del Sol Research Management - BTC (Site 130)
state: Arizona
city: Little Rock
country: United States
facility: Preferred Research Partners - ClinEdge (Site 103)
state: Arkansas
city: Little Rock
country: United States
facility: Applied Research Center (Site 158)
state: Arkansas
city: Bristol
country: United States
facility: Connecticut Clinical Research Foundation (Site 136)
state: Connecticut
city: Boynton Beach
country: United States
facility: Imagine Research of Palm Beach County (Site 187)
state: Florida
city: Lakeland
country: United States
facility: Meridien Research - Lakeland (Site 167)
state: Florida
city: Lauderdale Lakes
country: United States
facility: Precision Clinical Research LLC (Site 139)
state: Florida
city: Maitland
country: United States
facility: Meridien Research, Maitland - Inpatient (Site 141)
state: Florida
city: Oviedo
country: United States
facility: Oviedo Medical Research (Site 140)
state: Florida
city: Pompano Beach
country: United States
facility: Clinical Research Center of Florida (Site 186)
state: Florida
city: Saint Petersburg
country: United States
facility: Meridien Research - St. Petersburg (Site 132)
state: Florida
city: Atlanta
country: United States
facility: Agile Clinical Research Trials, LLC (Site 163)
state: Georgia
city: Columbus
country: United States
facility: Gastrointestinal Diseases, Inc. Research (Site 137)
state: Georgia
city: Savannah
country: United States
facility: Meridian Clinical Research (Site 169)
state: Georgia
city: Suwanee
country: United States
facility: In Quest Medical Research, LLC (Site 131)
state: Georgia
city: Valdosta
country: United States
facility: GNP Research (Site 145)
state: Georgia
city: Boise
country: United States
facility: Northwest Clinical Trials - ClinEdge (Site 133)
state: Idaho
city: Chicago
country: United States
facility: Synexus Clinical Research US, Inc. - Chicago (Site 120)
state: Illinois
city: Brownsburg
country: United States
facility: Investigators Research Group, LLC (Site 188)
state: Indiana
city: Evansville
country: United States
facility: Synexus Clinical Research US, Inc. - Allaw (Site 102)
state: Indiana
city: Wichita
country: United States
facility: Alliance for Multispecialty Research, LLC (Site 159)
state: Kansas
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center (Site 115)
state: Massachusetts
city: Richfield
country: United States
facility: AES-DRS-Synexus Clinical Research US, Inc.-Minneapolis (site 114)
state: Minnesota
city: Saint Louis
country: United States
facility: Sundance Clinical Research (Site 175)
state: Missouri
city: Omaha
country: United States
facility: Synexus Clinical Research US, Inc. - Omaha (Site 113)
state: Nebraska
city: Papillion
country: United States
facility: Synexus Clinical Research US, Inc. - McGill Family Practice, P.C. (Site 126)
state: Nebraska
city: Las Vegas
country: United States
facility: Jubilee Clinical Research - BTC (Site 162)
state: Nevada
city: Las Vegas
country: United States
facility: Sierra Clinical Research (Site 179)
state: Nevada
city: Albuquerque
country: United States
facility: Lovelace Scientific Resources Inc. (Site 176)
state: New Mexico
city: Brooklyn
country: United States
facility: NY Scientific (Site 153)
state: New York
city: Great Neck
country: United States
facility: Long Island Gastrointestinal Research Group LLP (Site 107)
state: New York
city: Jamaica
country: United States
facility: Synexus Clinical Research US, Inc. - Queens (Site 119)
state: New York
city: Newburgh
country: United States
facility: Mid Hudson Medical Research PLLC (Site 174)
state: New York
city: Williamsville
country: United States
facility: Upstate Clinical Research Associates LLC - ClinEdge (Site 164)
state: New York
city: Charlotte
country: United States
facility: OnSite Clinical Solutions, LLC - ClinEdge (Site 147)
state: North Carolina
city: Charlotte
country: United States
facility: OnSite Clinical Solutions, LLC - ClinEdge (Site 146)
state: North Carolina
city: High Point
country: United States
facility: Peters Medical Research, LLC - ClinEdge (SIte 111)
state: North Carolina
city: Salisbury
country: United States
facility: PMG Research of Salisbury LLC (Site 110)
state: North Carolina
city: Wilmington
country: United States
facility: PMG Research of Wilmington (Site 185)
state: North Carolina
city: Winston-Salem
country: United States
facility: PMG Research of Winston-Salem (Site 124)
state: North Carolina
city: Akron
country: United States
facility: Synexus Clinical Research US, Inc. - Akron (Site 122)
state: Ohio
city: Cincinnati
country: United States
facility: Hometown Urgent Care and Research (Site 150)
state: Ohio
city: Cincinnati
country: United States
facility: Synexus Clinical Research US, Inc. - Cincinnati (Site 127)
state: Ohio
city: Columbus
country: United States
facility: Synexus Clinical Research US, Inc. - Columbus (Site 108)
state: Ohio
city: Columbus
country: United States
facility: Hometown Urgent Care and Research (Site 149)
state: Ohio
city: Columbus
country: United States
facility: Remington Davis Inc (Site 144)
state: Ohio
city: Dayton
country: United States
facility: PriMed Clinical Research - ClinEdge (Site 121)
state: Ohio
city: Dayton
country: United States
facility: Hometown Urgent Care and Research (Site 151)
state: Ohio
city: Oklahoma City
country: United States
facility: Medical Research international (Site 180)
state: Oklahoma
city: Philadelphia
country: United States
facility: Tristar Clinical Investigations, P.C. (Site 168)
state: Pennsylvania
city: Uniontown
country: United States
facility: Frontier Clinical Research, LLC (Site 171)
state: Pennsylvania
city: Fort Mill
country: United States
facility: Piedmont Research Partners LLC - BTC (Site 157)
state: South Carolina
city: Greer
country: United States
facility: Synexus clinical Research US, Inc. - Greer (Site 105)
state: South Carolina
city: Chattanooga
country: United States
facility: WR-ClinSearch, LLC (Site 129)
state: Tennessee
city: Jackson
country: United States
facility: The Jackson Clinic PA - ClinEdge (Site 135)
state: Tennessee
city: Knoxville
country: United States
facility: New Phase Research & Development (Site 181)
state: Tennessee
city: Austin
country: United States
facility: Benchmark Research - Austin (Site 178)
state: Texas
city: Georgetown
country: United States
facility: Advanced Medical Trials (SIte 142)
state: Texas
city: Houston
country: United States
facility: Pioneer Research Solutions (Site 125)
state: Texas
city: Missouri City
country: United States
facility: Synergy Group US, LLC - Missouri City - Hunt (Site 156)
state: Texas
city: Pearland
country: United States
facility: DM Clinical Research - LinQ Research - ERN (Site 109)
state: Texas
city: San Antonio
country: United States
facility: Synexus Clinical Research US, Inc. - San Antonio (Site 112)
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas Incorporated - ClinEdge (Site 134)
state: Texas
city: Murray
country: United States
facility: Synexus Clinical Research US, Inc. - Salt Lake City (Site 101)
state: Utah
city: Ogden
country: United States
facility: Advanced Research Institute (Site 117)
state: Utah
city: Newport News
country: United States
facility: Health Research of Hampton Roads Inc. (Site 173)
state: Virginia
city: Petersburg
country: United States
facility: The Center of Gastrointestinal Health (Site 152)
state: Virginia
city: Bellevue
country: United States
facility: Northwest Clinical Research Center - ClinEdge (Site 148)
state: Washington
city: Morgantown
country: United States
facility: Exemplar Research, Inc. - Morgantown (Site 172)
state: West Virginia
Study officials:
References: