0760 SUVN-G3031, A Potent And Selective Histamine H3 Receptor Inverse Agonist: Safety, Tolerability And Pharmacokinetics Following Single And Multiple Ascending Doses In Healthy Adult Subjects

Abstract Introduction SUVN-G3031 is a potent and selective histamine H3 receptor inverse agonist currently being developed for the treatment of narcolepsy. SUVN-G3031 produced robust wake promoting and anticataplectic effects in animal model relevant to the disease. This supports its therapeutic utility in the treatment of sleep related disorders like narcolepsy with and without cataplexy. Methods Two Phase 1 studies were conducted to assess safety, tolerability and pharmacokinetics (PK) of SUVN-G3031. In the first study, single ascending doses of 0.1 mg to 20 mg SUVN-G3031 were administered to healthy subjects. For multiple ascending dose cohorts, doses of 1 mg to 6 mg were administered for 14 days. In the second Phase 1 study, effects of food, gender and age on the PK of SUVN-G3031 were assessed. Results SUVN-G3031 absorbed rapidly following single oral administration and the exposures (Cmax and AUC) were dose proportional at the tested doses between 0.1 mg to 20 mg. SUVN-G3031 attained steady state on day six and achieved projected efficacy concentrations following repeated administrations. Food, gender and age had no effect on pharmacokinetics of SUVN-G3031. SUVN-G3031 was well tolerated up to 20 mg/ day single dose and 6 mg repeated dose in healthy adult subjects. There were no serious adverse events reported by any subject during Phase 1 studies. Conclusion SUVN-G3031 was well tolerated in humans with adequate plasma exposures for efficacy and has favorable pharmacokinetics suitable for once a day oral administration. SUVN-G3031 is currently being evaluated in a Phase 2 study as monotherapy for the treatment of narcolepsy with and without cataplexy (ClinicalTrials.gov Identifier: NCT04072380). Support None