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 mg or 100 mg three times daily (TID) 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 (standard deviation [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.
Conclusion
Patients with quiescent to mildly active CD receiving olorinab experienced mild-to-moderate AEs and an improvement in abdominal pain scores in this study.
Olorinab (APD371), a peripherally acting, highly selective, full agonist of the cannabinoid receptor 2, reduces colitis-induced acute and chronic visceral hypersensitivity in rodents
