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

Irritable Bowel Syndrome With Diarrhea Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04129619
• Other study ID #: OM-201
• Status: Completed
• Phase: Phase 2
• Start date: November 22, 2019
• Est. completion date: October 4, 2021

Study information

• Verified date: March 2022
• Source: OrphoMed, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 321
• Est. completion date: October 4, 2021
• Est. primary completion date: October 4, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diarrhea
• Irritable Bowel Syndrome
• Irritable Bowel Syndrome With Diarrhea
• Syndrome

Intervention

Drug:
• ORP-101
Oral tablet
• Placebo
Oral tablet

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
OrphoMed, Inc.	PPD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change from Baseline in Daily Abdominal Discomfort Scores	Discomfort: Change from baseline in daily abdominal discomfort scores	Week 12
Secondary	Change from Baseline in Daily Abdominal Bloating Scores	Bloating: Change from baseline in daily abdominal bloating scores	Week 12
Secondary	Number of Bowel Movements Per Day	Frequency: Change from baseline in mean number of bowel movements per day	Week 12
Secondary	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

External Links

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