Effect of Olorinab on Gastrointestinal Transit in Patients With Irritable Bowel Syndrome

Study Overview
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Brief Summary
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A Phase 1b study to determine the effect of oral olorinab on gastrointestinal transit in adult participants with irritable bowel syndrome (IBS).

Detailed Description
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This is a single-center, randomized, crossover, double-blind, placebo-controlled study designed to evaluate the effects of olorinab on gastric, small-bowel, and colonic transit in IBS participants with predominant constipation (IBS-C) or with predominant diarrhea (IBS-D).

Official Title
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Effect of Olorinab on Gastrointestinal Transit in Patients With Irritable Bowel Syndrome

Conditions
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Irritable Bowel Syndrome

Intervention / Treatment
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* Drug: Olorinab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of irritable bowel syndrome (IBS) with predominant constipation (IBS-C) or IBS with predominant diarrhea (IBS-D) according to Rome IV criteria at Screening Body mass index (BMI) 18.0 to 40.0 kilograms per square meter (kg/m^2), inclusive at Screening Negative test results for alcohol and selected drugs at Screening and Day 1 Negative hepatitis panel (including hepatitis B surface antigen [HBsAg] and hepatitis C virus antibody [anti-HCV]) and negative for human immunodeficiency virus (HIV) antibody screens at Screening Participants with recent (within 6 months of Screening) or ongoing alarm features (unexplained weight loss, nocturnal symptoms, blood mixed with stool) are to have had a diagnostic colonoscopy prior to Screening and after the onset of alarm features (for participants with alarm features) to exclude non-IBS conditions per the Rome IV diagnostic algorithm for IBS Exclusion Criteria: Pregnant or lactating Structural or metabolic diseases/conditions that affect the gastrointestinal system Diagnosis of IBS with mixed bowel habits (IBS-M) or unsubtyped IBS (IBS-U) Unable to withdraw medications that alter gastrointestinal (GI) transit for 72 hours prior to baseline colonic transit assay through the duration of treatment period, with the exception of rescue medicine usage (bisacodyl and loperamide) Clinically relevant changes in dietary, lifestyle, or exercise regimen within 30 days prior to Screening and for the duration of the study that may confound efficacy assessments in the clinical judgment of the Investigator (or designee)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olorinab, Then Placebo<br>Participants will first receive olorinab, followed by a washout period, and they then will receive placebo. | Drug: Olorinab<br>* Olorinab tablet by mouth, 3 times a day for 4 days with a final dose on Day 5.<br>Drug: Placebo<br>* Olorinab matching placebo tablet by mouth, 3 times a day for 4 days with a final dose on Day 5.<br>|
| Placebo Comparator: Placebo, Then Olorinab<br>Participants will first receive placebo, followed by a washout period, and they then will receive olorinab. | Drug: Olorinab<br>* Olorinab tablet by mouth, 3 times a day for 4 days with a final dose on Day 5.<br>Drug: Placebo<br>* Olorinab matching placebo tablet by mouth, 3 times a day for 4 days with a final dose on Day 5.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Colonic transit geometric center after consumption of radiolabeled meal, based on the delivery of activated charcoal in a methacrylate-coated capsule |  | up to 24 hours 30 minutes after consumption of radiolabeled meal | 
| Gastric emptying half-life (t½) as determined by scintigraphic imaging of radiolabeled meal |  | up to 4 hours 10 minutes after consumption of radiolabeled meal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Colonic transit geometric center after consumption of radiolabeled meal, based on the delivery of activated charcoal in a methacrylate-coated capsule |  | up to 48 hours 30 minutes after consumption of radiolabeled meal | 
| Ascending colon emptying t½ of radiolabeled activated charcoal particles delivered in a methacrylate-coated capsule |  | up to 24 hours 30 minutes after consumption of radiolabeled meal | 
| Gastric emptying after radiolabeled meal |  | at 2 hours ± 10 minutes and 4 hours ± 10 minutes after consumption of radiolabeled meal | 
| Number and severity of adverse events | Safety will be assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results. | Up to approximately 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Olorinab, APD371, Irritable bowel syndrome, IBS, IBS with predominant constipation, IBS-C, IBS with predominant diarrhea, IBS-D