Tolerability, Pharmacokinetics, and Efficacy of APD371 in Participants With Crohn's Disease Experiencing Abdominal Pain

A Randomized, Open-label, Parallel, Phase 2a Study to Determine the Tolerability, Pharmacokinetics, and Efficacy of APD371 in Participants With Crohn's Disease Experiencing Abdominal Pain

The purpose of this randomized, open-label, parallel, phase 2a study is to determine the tolerability, pharmacokinetics, and efficacy of olorinab in participants with Crohn's disease experiencing abdominal pain.

Study Overview

• Status: Completed
• Conditions: Abdominal Pain; Crohn's Disease
• Intervention / Treatment: Drug: Olorinab

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Brandon, Florida, United States, 33511
      • Clinical Research of Brandon
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Medical Center
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • Wake Research Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati Medical Center
  • Washington
    • Tacoma, Washington, United States, 98405
      • MultiCare Institute for Research and Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• A clinical diagnosis of Crohn's disease for at least 3 months prior to screening corroborated by prior endoscopic and histopathologic documentation consistent with Crohn's disease.
• Quiescent to mildly active inflammatory Crohn's disease defined with a total of simple endoscopy score for Crohn's disease (SES-CD) score of < 10 or fecal calprotectin < 500 mcg/g within 4 weeks before Screening.
• Moderate to severe abdominal pain as defined by average abdominal pain score (AAPS) of >/= 4points on 7 consecutive days of the screening period up to Day -2. AAPS will be based on the 11-point numeric rating scale where 0 (no abdominal pain) to 10 (worst possible abdominal pain).

Key Exclusion Criteria:

• Female participants who are lactating or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 prior to study drug administration.
• Recent history (within 6 months of screening visit) of cerebrovascular disease, Acute Coronary Syndrome, Cerebrovascular accident, Transient ischemic attack, Myocardial infarction, unstable angina.
• Other significant chronic pain conditions that in the opinion of the Investigator may influence the abdominal pain score.
• History of extensive colonic resection, subtotal or total colectomy.
• History of >3 small bowel resections or diagnosis of short bowel syndrome or who have undergone bowel resection within 6 months prior to randomization.
• Chronic active hepatitis B within the last year (unless shown at the time of study entry to be hepatitis B antigen negative) or any history of hepatitis C.
• Evidence of current gastro-intestinal infection (bacterial or parasitic) or significant infection within 45 days of screening.

Note: other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Olorinab 25 mg TID; Participants received olorinab 25 milligrams (mg) tablet by mouth, three times daily (TID) for 8 weeks	Drug: Olorinab; Olorinab active treatment for 8 weeks.; Other Names: APD371
Experimental: Olorinab 100 mg TID; Participants received olorinab 100 mg oral tablets TID for 8 weeks	Drug: Olorinab; Olorinab active treatment for 8 weeks.; Other Names: APD371

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	TEAE was defined as an adverse event (AE) that occurred after first dose of olorinab. A SAE was any untoward medical occurrence that at any dose resulted in the following outcomes: death, was life-threatening, required/prolonged hospitalization, disability/incapacity, congenital anomaly/birth defect, and important medical events. Safety was assessed by monitoring adverse events and clinically relevant changes in vital signs and clinical laboratory results.	Up to approximately 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory - Geometric Mean Maximum Observed Plasma Concentration (Cmax) of Olorinab and Its Metabolites at Week 8	The result for this exploratory endpoint was not reported.	Week 8: Pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose
Exploratory - Median Time for Cmax (Tmax) of Olorinab and Its Metabolites at Week 8	The result for this exploratory endpoint was not reported.	Week 8: Pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose
Exploratory - Mean Area Under the Concentration Time Curve From Time of Dosing to 8 Hours Post-dose (AUC0-8) of Olorinab and Its Metabolites at Week 8	The result for this exploratory endpoint was not reported.	Week 0 (Day 1, Day 2), Week 8 (Day -1), Week 8: Pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose
Exploratory - Mean Change in Abdominal Pain Score (APS) From Trough to Peak at Week 8	The result for this exploratory endpoint was not reported.	Baseline; Week 8
Exploratory - Change From Baseline in Average APS (AAPS)	The result for this exploratory endpoint was not reported.	Baseline; Week 1, 2, 4, 6 and 8
Exploratory - Number of Participants Who Were End-of-treatment Responders	The result for this exploratory endpoint was not reported.	Week 8
Exploratory - Number of Participants Who Were Weekly Responders	The result for this exploratory endpoint was not reported.	Weeks 1, 2, 4, 6, and 8
Exploratory - Number of Pain-free Days Per Week	The result for this exploratory endpoint was not reported.	Week 1, Week 2, Week 4, Week 6, Week 8, and end of treatment
Exploratory - Number of Participants Who Used Pain Rescue Medication	The result for this exploratory endpoint was not reported.	Up to Week 8
Exploratory - Change From Baseline in C-reactive Protein (CRP) Levels at Week 4 and Week 8	The result for this exploratory endpoint was not reported.	Baseline, Week 4, Week 8
Exploratory - Change From Baseline in Fecal Calprotectin Levels at Week 4 and Week 8	The result for this exploratory endpoint was not reported.	Baseline, Week 4, Week 8

Collaborators and Investigators

• Sponsor: Arena Pharmaceuticals

Publications and helpful links

General Publications

• Castro J, Garcia-Caraballo S, Maddern J, Schober G, Lumsden A, Harrington A, Schmiel S, Lindstrom B, Adams J, Brierley SM. Olorinab (APD371), a peripherally acting, highly selective, full agonist of the cannabinoid receptor 2, reduces colitis-induced acute and chronic visceral hypersensitivity in rodents. Pain. 2022 Jan 1;163(1):e72-e86. doi: 10.1097/j.pain.0000000000002314.

Helpful Links

• Safety, Pharmacokinetics, and Efficacy of Olorinab, a Peripherally Acting, Highly Selective, Full Agonist of the Cannabinoid Receptor 2, in a Phase 2a Study of Patients With Chronic Abdominal Pain Associated With Crohn's Disease

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2017
• Primary Completion (Actual): September 10, 2018
• Study Completion (Actual): September 10, 2018

Study Registration Dates

• First Submitted: May 11, 2017
• First Submitted That Met QC Criteria: May 15, 2017
• First Posted (Actual): May 16, 2017

Study Record Updates

• Last Update Posted (Actual): November 2, 2021
• Last Update Submitted That Met QC Criteria: October 5, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms, Digestive; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Abdominal Pain; Crohn Disease
• Other Study ID Numbers: APD371-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No