PI-014 - RESULTS OF A PHASE 1 CLINICAL TRIAL (GH001-HV-103) TO DETERMINE THE SAFETY AND TOLERABILITY OF MEBUFOTENIN (5-MEO-DMT), ADMINISTERED VIA INHALATION (GH001) IN HEALTHY SUBJECTS.

P. Dogterom¹, T. Terwey², C. Svendsen², P. O'Grady², K. Abd-Elaziz³; ¹QPS Netherlands, QPS Netherlands, Groningen, The Netherlands, ²GH Research, Dublin, Ireland, ³QPS Netherlands, Groningen, Netherlands.

Background: Mebufotenin (5-MeO-DMT) is a potent psychoactive compound of the tryptamine class. It acts as a non-selective serotonin (5-HT) agonist with highest affinity for the 5-HT1A receptor. A previous open-label, Phase 1 trial in healthy subjects indicated that pulmonary inhalation of mebufotenin as GH001 is well tolerated when administered as single doses or as an individualized dosing regimen (IDR) of up to three escalating doses. We report data from an additional Phase 1 clinical trial (NCT05163691) that extended the investigation of the safety and tolerability of GH001, administered as single escalating doses or as an IDR.

Methods: Forty-six healthy male and female subjects, aged 18 to ˂ 65 years, participated in this trial. In Part 1, which had a double-blind, randomized design, single escalating doses of GH001 (6, 12 and 18 mg) or placebo (8:2 per dose level) were administered. Part 2 had an open-label design in which GH001 was administered as an IDR of up to three escalating doses (6, 12 and 18 mg). There was a scheduled interval of 1 hour (cohort 1, n=8) or 2 hours (cohort 2, n=8) between subsequent doses in the IDR.
All enrolled subjects in Parts 1 and 2 were dosed as per the protocol and monitored individually on Day 1 with follow-up visits for safety on Days 7 and 30.

Results: All treatment-emergent adverse events (TEAEs) were mild in severity and resolved spontaneously. There were no SAEs.
In Part 1, a total of 20 TEAEs were reported by 12/24 subjects receiving GH001. The most commonly reported TEAEs were headache, crying, and tachycardia. A higher percentage of subjects in the 18 mg group experienced a TEAE.
In Part 2, a total of 12 TEAEs were reported by 9/16 subjects. The most commonly reported TEAEs were fatigue, crying, headache and nasal congestion.
Temporary increases in heart rate and blood pressure were observed shortly after administration of GH001 but were deemed not clinically relevant and there were no other noteworthy changes in vital signs parameters. Additionally, no clinically relevant changes in ECG, safety laboratory analyses, peak flow, cognitive function, or psychiatric symptom scales, including the C-SSRS, were reported.

Conclusion: This trial demonstrated that GH001 administered via inhalation as single doses or as an IDR was well tolerated at the tested doses in healthy subjects.