Pharmacokinetics of GH001 Delivered Via a Proprietary Aerosol Delivery Device in Healthy Subjects
NCT Number: NCT06511947
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: Healthy Volunteers
Interventions: DRUG: 5 Methoxy N,N Dimethyltryptamine
Sponsor: GH Research Ireland Limited
Sex: ALL
Age: ADULT
Enrollment: 52
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: PARALLEL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-08-01
Completion Date: 2025-02
Locations: GH Research Clinical Trial Site, London, United Kingdom

Summary:
The primary objectives of this trial are to determine the pharmacokinetic (PK) profile and the safety and tolerability of GH001 delivered via a proprietary aerosol delivery device in healthy subjects after single-dose administration and a single-day individualized dosing regimen (IDR). As secondary objectives, the mebufotenin PK/ pharmacodynamic (PD) relationship, the PD profile of GH001 as evaluated by its psychoactive effects (PsE), the impact on cognitive performance, and the TCmax/2 and TCmax/10 (time taken for Cmax to decrease by 50 and 90%, respectively) are also assessed.

Primary Outcome Measures: Serum PK parameters of mebufotenin - maximum observed concentration (Cmax), For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations., Up to 6 hours|Serum PK parameters of mebufotenin - time of maximum observed concentration (Tmax), For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations., Up to 6 hours|Serum PK parameters of mebufotenin - terminal elimination half-life (t1/2), For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations., Up to 6 hours|Serum PK parameters of mebufotenin - area under the serum concentration-time curve from time zero to the last quantifiable concentration (AUC0-t), For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations., Up to 6 hours|Serum PK parameters of mebufotenin - area under the serum concentration-time curve extrapolated to infinity (AUC0-∞), For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations., Up to 6 hours|Serum PK parameters of mebufotenin - terminal elimination rate constant (λz), For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations., Up to 6 hours|Serum PK parameters of mebufotenin - apparent total body clearance (CL/F), For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations., Up to 6 hours|Serum PK parameters of mebufotenin - apparent steady-state volume of distribution (VSS/F), For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations., Up to 6 hours|Serum PK parameters of mebufotenin - Cmax/AUC0-∞, For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations., Up to 6 hours|Safety and tolerability: incidence of treatment-emergent adverse events, Adverse events reported in the study and coded by MedDRA., Up to 7 days|Safety and tolerability: clinically significant changes from baseline in electrocardiogram (ECG), vital signs, spirometry and safety laboratory assessments, Percentage of subjects with clinically significant changes\* from baseline in ECG (heart rate, RR, QT, PR, and QRS intervals, and QTcF).

Percentage of subjects with clinically significant changes\* from baseline in vital signs (systolic and diastolic blood pressure, respiration rate, heart rate, peripheral oxygen saturation, body temperature).

Percentage of subjects with clinically significant changes\* from baseline in spirometry (forced expiratory volume in 1 second \[FEV1\] and forced vital capacity \[FVC\]).

Percentage of subjects with clinically significant changes\* from baseline in safety laboratory assessments (hematology, biochemistry, and urinalysis).

\*Clinically significant changes as determined by the principal investigator, Up to 7 days|Safety and tolerability: assessment of sedation (Modified Observer's Assessment of Alertness and Sedation [MOAA/S]) following each dose and as part of the discharge evaluation on Day 0, The MOAA/S will be completed before and after GH001 dosing. Scored from 0 (deep sedation) to 5 (alert)., Postdose, up to discharge on dosing day (Day 0)|Safety and tolerability: change from baseline in Clinician Administered Dissociative States Scale (CADSS), The CADSS comprises 19 subjective items, ranging from 0 'not at all' to 4 'extremely. Summed together, these subscales form a total dissociative score. Combined score ranges from 0 to 76., From baseline up to 7 days|Safety and tolerability: assessment of subject discharge readiness at discharge on Day 0, Assessment of Discharge Readiness on the administration day by the principal investigator, using the Clinical Assessment of Discharge Readiness (CADR)., Postdose, at discharge on dosing day (Day 0)|Safety and tolerability: Columbia-Suicide Severity Rating Scale (C-SSRS) categorization., A detailed questionnaire assessing both suicidal behaviour and suicidal ideation., Up to 7 days|Safety and tolerability: Change from baseline in Brief Psychiatric Rating Scale (BPRS)., A scale to measure psychiatric symptoms. Each symptom is rated 1-7 and a total of 18 symptoms are scored. Combined score ranges from 18 to 126 and a higher score means a worse outcome., From baseline up to 7 days