Olorinab in Irritable Bowel Syndrome With Predominant Constipation (IBS-C) and Irritable Bowel Syndrome With Predominant Diarrhea (IBS-D)

Irritable Bowel Syndrome Clinical Trial

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Official title:

A Phase 2, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Parallel-Group Study to Evaluate the Safety, Tolerability, and Efficacy of Olorinab in Subjects With Irritable Bowel Syndrome Experiencing Abdominal Pain

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04043455
• Other study ID #: APD371-202
• Status: Terminated
• Phase: Phase 2
• Start date: July 24, 2019
• Est. completion date: April 29, 2021

Study information

• Verified date: September 2022
• Source: Arena Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether olorinab is a safe and effective treatment for abdominal pain in participants with irritable bowel syndrome (IBS).

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 273
• Est. completion date: April 29, 2021
• Est. primary completion date: April 29, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Main Study Inclusion Criteria:

• Diagnosis of irritable bowel syndrome (IBS) with predominant constipation (IBS-C) or predominant diarrhea (IBS-D) according to Rome IV criteria at Visit 1 (Screening)

• Per the Rome IV diagnostic algorithm for IBS, participants 50 years of age and over are to have had one of the following with a result that rules out causes of abdominal pain other than IBS:

1. Colonoscopy (within 10 years of Visit 1 [Screening])

2. Flexible sigmoidoscopy and double contrast barium enema (within 5 years of Visit 1 [Screening])

3. Computed tomography colonography (within 5 years of Visit 1 [Screening])

Main Study Exclusion Criteria:

• Diagnosis of IBS with mixed bowel habits (IBS-M) or unsubtyped IBS (IBS-U)

• Clinically relevant changes in dietary, lifestyle, or exercise regimen within 30 days prior to Visit 1 (Screening) that may confound efficacy assessments in the clinical judgment of the Investigator (or designee)

• Any colonic or major abdominal surgery (eg, bariatric surgery [including gastric banding], stomach surgery, small/large bowel surgery, or abdominal large vessel surgery). History of cholecystectomy is exclusionary for participants with IBS-D. For participants with IBS-C, a history of cholecystectomy more than 6 months prior to Visit 1 (Screening) is allowed. Procedures such as appendectomy, hysterectomy, caesarean section, or polypectomy are allowed as long as they have occurred at least 3 months prior to Visit 1 (Screening).

Long-Term Extension Inclusion Criteria:

•All participants must have completed the Main Study (including both Visit 8 [Week 12] and Visit 9 [Week 14])

Long-Term Extension Exclusion Criteria:

• Participant meets any exclusion criteria from the Main Study at the time of assessing eligibility for the LTE, unless approved by the Sponsor in advance.

• Participant had less than 75% overall compliance with eDiary entries during the Main Study.

• Participant deviated from the prescribed dosage regimen during the Main Study (ie, overall study treatment compliance less than 85% or more than 115%), unless approved by the Sponsor in advance.

Related Conditions & MeSH terms

• Irritable Bowel Syndrome
• Syndrome

Intervention

Drug:
• Olorinab
Olorinab Dose 1 capsule or tablet by mouth, 3 times per day up to 12 weeks
• Olorinab
Olorinab Dose 2 capsule or tablet by mouth, 3 times per day up to 12 weeks
• Olorinab
Olorinab Dose 3 capsule or tablet by mouth, 3 times per day up to 12 weeks
• Placebo
Olorinab matching placebo capsule or tablet by mouth, 3 times per day up to 12 weeks
• Olorinab
Olorinab Dose 2 capsule or tablet by mouth, 3 times per day up to 52 weeks
• Olorinab
Olorinab Dose 3 capsule or tablet by mouth, 3 times per day up to 52 weeks

Locations

Country	Name	City	State
United States	Agile Clinical Research Trials LLC	Atlanta	Georgia
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	Lynn Institute of Denver	Aurora	Colorado
United States	Great Lakes Medical Research	Beachwood	Ohio
United States	Hassman Research Institute	Berlin	New Jersey
United States	Accel Research Sites - Birmingham Clinical Research Unit	Birmingham	Alabama
United States	Clinical Research of Brandon, LLC	Brandon	Florida
United States	Alliance Research Institute	Canoga Park	California
United States	East Valley Gastroenterology and Hepatology Associates	Chandler	Arizona
United States	Clinical Trials of South Carolina	Charleston	South Carolina
United States	Chattanooga Research & Medicine, PLLC	Chattanooga	Tennessee
United States	WR-ClinSearch, LLC	Chattanooga	Tennessee
United States	Claude Mandel Medical Center	Chicago	Illinois
United States	New River Valley Research Institute	Christiansburg	Virginia
United States	GW Research, Inc.	Chula Vista	California
United States	Rapid Medical Research, Inc.	Cleveland	Ohio
United States	Columbus Regional Research Institute	Columbus	Georgia
United States	Kindred Medical Institute for Clinical Trials, LLC	Corona	California
United States	Meridian Clinical Research, LLC	Dakota Dunes	South Dakota
United States	TriWest Research Associates, LLC	El Cajon	California
United States	Diagnamics Inc.	Encinitas	California
United States	MediSphere Medical Research Center, LLC	Evansville	Indiana
United States	Flint Clinical Research, PLLC	Flint	Michigan
United States	Frederick Gastroenterology Associates	Frederick	Maryland
United States	Gastroenterology Associates of Gainesville Georgia	Gainesville	Georgia
United States	Clinical Research of Gastonia	Gastonia	North Carolina
United States	Gilbert Center for Family Medicine	Gilbert	Arizona
United States	Long Island Gastrointestinal Research Group LLP	Great Neck	New York
United States	Medication Management, LLC	Greensboro	North Carolina
United States	Susquehanna Research Group, LLC	Harrisburg	Pennsylvania
United States	Peters Medical Research, LLC	High Point	North Carolina
United States	CroNOLA, LLC	Houma	Louisiana
United States	Biopharma Informatic, LLC	Houston	Texas
United States	Clinical Trial Network	Houston	Texas
United States	Clinical Research Associates, LLC	Huntsville	Alabama
United States	University of Iowa Hospitals and Clinics	Iowa City	Iowa
United States	Research Studies at Fine Digestive Health	Irving	Texas
United States	Center for Pharmaceutical Research, LLC an AMR company	Kansas City	Missouri
United States	Prime Care Clinical Research	Laguna Hills	California
United States	Clinical Trials of SWLA, LLC	Lake Charles	Louisiana
United States	Om Research, Attn: Heather Blunt	Lancaster	California
United States	Clinical Neuroscience Solutions, Inc.	Memphis	Tennessee
United States	Great Lakes Gastroenterology Research, LLC	Mentor	Ohio
United States	Advanced Clinical Research, Attn to: Owen Havey	Meridian	Idaho
United States	Exemplar Research Inc	Morgantown	West Virginia
United States	Coastal Carolina Research Center	Mount Pleasant	South Carolina
United States	Central Sooner Research	Norman	Oklahoma
United States	Lemah Creek Clinical Research	Oakbrook Terrace	Illinois
United States	Digestive Disease Specialists, Inc.	Oklahoma City	Oklahoma
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Care Access Research, Pottsville	Pottsville	Pennsylvania
United States	M3 Wake Research	Raleigh	North Carolina
United States	Clinical Research of Rock Hill	Rock Hill	South Carolina
United States	Oregon Center for Clinical Investigations, Inc. (OCCI, Inc.)	Salem	Oregon
United States	Medical Associates Research Group	San Diego	California
United States	Precision Research Institute	San Diego	California
United States	San Diego Gastroenterology Medical Associates (CTNx)	San Diego	California
United States	WR-Mount Vernon Clinical Research, LLC	Sandy Springs	Georgia
United States	WestGlenGI	Shawnee Mission	Kansas
United States	Louisiana Research Center, LLC	Shreveport	Louisiana
United States	Qps Mra, Llc	South Miami	Florida
United States	Clinical Research Atlanta	Stockbridge	Georgia
United States	Precision Clinical Research, LLC.	Sunrise	Florida
United States	MultiCare Institute for Research & Innovation	Tacoma	Washington
United States	Presicion Research Center Inc	Tampa	Florida
United States	Lynn Institute of Tulsa	Tulsa	Oklahoma
United States	Family Practice Center of Wadsworth, Inc. dba New Venture Medical Research	Wadsworth	Ohio
United States	ACR Gut Whisperer	West Jordan	Utah
United States	Advanced Rx Clinical Research Group, Inc.	Westminster	California

Sponsors (1)

Lead Sponsor	Collaborator
Arena Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Main Study: Change From Baseline in Average Abdominal Pain Score (AAPS) at Week 12	The APS is a single question, 11-point numeric rating scale in which 0 represents no abdominal pain and 10 represents the worst possible abdominal pain. The change in AAPS from Baseline at Week 12 was analyzed using a mixed-effects model repeated measures (MMRM) analysis with treatment, stratification factors, week, and treatment-by-week interaction as factors and Baseline AAPS as a covariate. An unstructured variance-covariance matrix was used for the MMRM analysis.	Baseline and Week 12
Primary	Main Study: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	An adverse event (AE) was any untoward medical occurrence in a participant administered a medicinal product without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as any AE that started or worsened in severity on or after the first dose of study treatment.	Up to 14 Weeks
Primary	LTE Period: Number of Participants With TEAEs and SAEs	An AE was any untoward medical occurrence in a participant administered a medicinal product without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. TEAEs were defined as any AE that started or worsened in severity on or after the first dose of study treatment.	Up to 54 Weeks
Primary	Main Study: Number of Participants With Clinically Significant Abnormal Laboratory Parameters	Blood samples were collected for the analysis of laboratory parameters including serum chemistry, hematology, coagulation, and urinalysis. The investigator was responsible for reviewing laboratory results for clinically significant abnormalities.	Baseline to Week 14
Primary	LTE Study: Number of Participants With Clinically Significant Abnormal Laboratory Parameters	Blood samples were collected for the analysis of laboratory parameters including serum chemistry, hematology, coagulation, and urinalysis. The investigator was responsible for reviewing laboratory results for clinically significant abnormalities.	Baseline to Week 54 (of LTE)
Primary	Main Study: Number of Participants With Clinically Significant Abnormal Vital Signs	Parameters assessed for vital signs included blood pressure (systolic and diastolic blood pressure), heart rate (HR), body temperature, and respiratory rate. The investigator was responsible for reviewing vital signs for clinically significant abnormalities.	Baseline to Week 14
Primary	LTE Study: Number of Participants With Clinically Significant Abnormal Vital Signs	Parameters assessed for vital signs included blood pressure (systolic and diastolic blood pressure), HR, body temperature, and respiratory rate. The investigator was responsible for reviewing vital signs for clinically significant abnormalities.	Baseline to Week 54 (of LTE)
Secondary	Main Study: Percentage of Participants Achieving a Greater Than or Equal to (>=) 30% Improvement in AAPS at Week 12	The percentage of participants achieving a >= 30% improvement in AAPS from Baseline at Week 12 was analyzed using a Cochran-Mantel-Haenszel (CMH) test stratified by the stratification factors. Missing post-baseline AAPS data was imputed using multiple imputation (MI) under the missing at random (MAR) assumption. Participants who were randomized but did not have at least 1 post-Baseline observation were considered non-responders. A >= 30% improvement in AAPS was a reduction in AAPS of 30% or more when compared to Baseline AAPS.	Baseline and Week 12
Secondary	Main Study: Percentage of Participants Achieving a >= 30% Improvement in AAPS From Baseline for at Least 6 of the 12 Weeks	The percentage of participants achieving a >= 30% improvement in AAPS from Baseline for at least 6 of the 12 weeks during the Treatment Period were analyzed using a CMH test stratified by the stratification factors. A >= 30% improvement in AAPS is a reduction in AAPS of 30% or more when compared to Baseline AAPS. Missing post-baseline AAPS data was imputed using MI under the MAR assumption.	Baseline and Week 12
Secondary	Main Study: Percent Change From Baseline in AAPS at Week 12	The percent change in AAPS from Baseline at Week 12 was analyzed using an MMRM analysis with treatment, stratification factors, week, and treatment-by-week interaction as factors and Baseline AAPS as a covariate. Baseline is the last non-missing measurement collected prior to the first dose of study treatment at Day 1.	Baseline and Week 12
Secondary	Main Study: Change From Baseline in Number of Pain-Free Days at Week 12	The change from Baseline at Week 12 in number of pain-free days per week was analyzed using a MMRM analysis with treatment, stratification factors, week, and treatment-by-week interaction as factors and Baseline pain free days as a covariate. Pain-free days were defined as days with a pain score of zero (0). Baseline is the last non-missing measurement collected prior to the first dose of study treatment at Day 1.	Baseline and Week 12
Secondary	Main Study: Maximum Concentration (Cmax) of Olorinab	Blood samples were collected from participants at indicated timepoints after the administration of study treatment to investigate Cmax of Olorinab. Pharmacokinetic (PK) analysis was conducted using standard non-compartmental methods.	On Day 1: Pre-dose and 0.5, 1, 2, 4, and 8 hours post dose and Week 4: Pre-dose and 0.5, 1 and 2 hours post dose
Secondary	Main Study: Time of Maximum Concentration After Drug Administration (Tmax) of Olorinab	Blood samples were collected from participants at indicated timepoints after the administration of study treatment to investigate Tmax of Olorinab. PK analysis was conducted using standard non-compartmental methods.	On Day 1: Pre-dose and 0.5, 1, 2, 4, and 8 hours post dose and Week 4: Pre-dose and 0.5, 1 and 2 hours post dose
Secondary	Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab	Blood samples were collected from participants at indicated time frames after the administration of study treatment to investigate Ctrough of Olorinab. PK analysis was conducted using standard non-compartmental methods.	Pre dose on Day 1, Day 2 and Weeks 2, 4, 8, 10 and 12