Olorinab in Irritable Bowel Syndrome With Predominant Constipation (IBS-C) and Irritable Bowel Syndrome With Predominant Diarrhea (IBS-D)
- Registration Number
- NCT04043455
- Lead Sponsor
- Arena Pharmaceuticals
- Brief 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 273
-
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:
- Colonoscopy (within 10 years of Visit 1 [Screening])
- Flexible sigmoidoscopy and double contrast barium enema (within 5 years of Visit 1 [Screening])
- Computed tomography colonography (within 5 years of Visit 1 [Screening])
Main Study
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Olorinab (Long-Term Extension) Olorinab Participants will receive olorinab based on their treatment assignment in the Main Study. Olorinab medium dose (Main Study) Olorinab - Olorinab high dose (Main Study) Olorinab - Placebo (Main Study) Placebo - Olorinab low dose (Main Study) Olorinab -
- Primary Outcome Measures
Name Time Method Main Study: Change From Baseline in Average Abdominal Pain Score (AAPS) at Week 12 Baseline and 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.
Main Study: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Up to 14 Weeks 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.
LTE Period: Number of Participants With TEAEs and SAEs Up to 54 Weeks 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.
Main Study: Number of Participants With Clinically Significant Abnormal Laboratory Parameters Baseline to Week 14 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.
LTE Study: Number of Participants With Clinically Significant Abnormal Laboratory Parameters Baseline to Week 54 (of LTE) 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.
Main Study: Number of Participants With Clinically Significant Abnormal Vital Signs Baseline to Week 14 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.
LTE Study: Number of Participants With Clinically Significant Abnormal Vital Signs Baseline to Week 54 (of LTE) 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.
- Secondary Outcome Measures
Name Time Method Main Study: Percentage of Participants Achieving a Greater Than or Equal to (>=) 30% Improvement in AAPS at Week 12 Baseline and 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.
Main Study: Percentage of Participants Achieving a >= 30% Improvement in AAPS From Baseline for at Least 6 of the 12 Weeks Baseline and Week 12 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.
Main Study: Percent Change From Baseline in AAPS at Week 12 Baseline and 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.
Main Study: Change From Baseline in Number of Pain-Free Days at Week 12 Baseline and 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.
Main Study: Maximum Concentration (Cmax) of Olorinab 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 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.
Main Study: Time of Maximum Concentration After Drug Administration (Tmax) of Olorinab 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 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.
Main Study: Plasma Trough Concentrations (Ctrough) of Olorinab Pre dose on Day 1, Day 2 and Weeks 2, 4, 8, 10 and 12 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.
Trial Locations
- Locations (69)
Accel Research Sites - Birmingham Clinical Research Unit
🇺🇸Birmingham, Alabama, United States
Clinical Research Associates, LLC
🇺🇸Huntsville, Alabama, United States
East Valley Gastroenterology and Hepatology Associates
🇺🇸Chandler, Arizona, United States
Gilbert Center for Family Medicine
🇺🇸Gilbert, Arizona, United States
Alliance Research Institute
🇺🇸Canoga Park, California, United States
GW Research, Inc.
🇺🇸Chula Vista, California, United States
Kindred Medical Institute for Clinical Trials, LLC
🇺🇸Corona, California, United States
TriWest Research Associates, LLC
🇺🇸El Cajon, California, United States
Diagnamics Inc.
🇺🇸Encinitas, California, United States
Prime Care Clinical Research
🇺🇸Laguna Hills, California, United States
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