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

Bruce R Yacyshyn; Stephen Hanauer; Preston Klassen; Brett A English; Kathe Stauber; Charles F Barish; Kye Gilder; Stewart Turner; Peter D R Higgins

doi:10.1093/crocol/otaa089

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

Crohns Colitis 360. 2020 Oct 24;3(1):otaa089. doi: 10.1093/crocol/otaa089. eCollection 2021 Jan.

Authors

Bruce R Yacyshyn¹, Stephen Hanauer², Preston Klassen³, Brett A English⁴, Kathe Stauber⁵, Charles F Barish⁶, Kye Gilder⁷, Stewart Turner⁸, Peter D R Higgins⁹

Affiliations

¹ Department of Gastroenterology, University of Cincinnati, Cincinnati, Ohio, USA.
² Department of Gastroenterology and Hepatology, Northwestern University, Chicago, Illinois, USA.
³ Arena Pharmaceuticals Inc., Research and Development, San Diego, California, USA.
⁴ Arena Pharmaceuticals Inc., Clinical Development, San Diego, California, USA.
⁵ Arena Pharmaceuticals Inc., Nonclinical Development and Clinical Pharmacology, San Diego, California, USA.
⁶ Department of Gastroenterology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.
⁷ Arena Pharmaceuticals Inc., Biostatistics and Data Management, San Diego, California, USA.
⁸ Arena Pharmaceuticals Inc., Olorinab Global Program Lead, San Diego, California, USA.
⁹ Department of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA.

Abstract

Background: This randomized, open-label phase 2a study investigated the safety/tolerability, pharmacokinetics, and efficacy of olorinab-a highly selective, peripherally acting, full agonist of the cannabinoid receptor 2-in patients with Crohn's disease (CD) experiencing abdominal pain.

Methods: Eligible subjects 18-80 years of age with quiescent to mildly active CD were randomized to receive olorinab 25 or 100 mg three times daily for 8 weeks. The primary objective was to assess safety/tolerability.

Results: Fourteen subjects received olorinab 25 mg (N = 6) or 100 mg (N = 8). Ten subjects [4 (67%) in the 25-mg group and 6 (75%) in the 100-mg group] reported a total of 34 treatment-emergent adverse events (TEAEs; 32 grade 1/2, not serious events; 2 grade 3, serious, not treatment-related events). No dose reductions or discontinuations due to TEAEs or deaths were reported. Dose-proportional increases in olorinab exposure from 25 to 100 mg were observed, with minimal accumulation at both doses. At week 8, the mean (SD) change from baseline in average abdominal pain score at peak olorinab plasma concentrations was -4.61 (1.77) in the 25-mg group (P = 0.0043) and -4.57 (2.17) in the 100-mg group (P = 0.0036). The change from baseline at week 8 in the mean (SD) number of pain-free days per week was +1.60 (2.61) in the 25-mg group and +2.33 (3.62) in the 100-mg group. No subject required pain medication on study.

Conclusions: Patients with quiescent to mildly active CD receiving olorinab experienced mild-to-moderate adverse events and an improvement in abdominal pain scores in this study.

Keywords: CB2 agonist; Crohn’s disease; cannabinoid; olorinab; pain.