Pharmacokinetics of GH001 Delivered Via a Proprietary Aerosol Delivery Device in Healthy Subjects

An Open-label Phase 1 Trial to Determine the Pharmacokinetics, Pharmacodynamics, and Safety of GH001 Administered Via a Proprietary Aerosol Delivery Device in Healthy Subjects

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.

Study Overview

• Status: Recruiting
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: 5 Methoxy N,N Dimethyltryptamine

• Study Type: Interventional
• Enrollment (Estimated): 52
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: GH Research Limited Clinical Trial Enquiries; Phone Number: +353 87 450 3237; Email: clinicaltrials@ghres.com

Study Locations

• United Kingdom
  • London, United Kingdom
    • Recruiting
    • GH Research Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Body mass index (BMI) in the range of 18.5 to 35 kg/m2 (inclusive) at screening
• Good mental health in the opinion of the investigator.
• Normal spirometry (FEV1 of >80% of predicted and FVC of >80% of predicted value) at screening.

Exclusion Criteria:

• Has known allergies or hypersensitivity or any other contraindication to mebufotenin, bufotenin, melatonin or triptans.
• Has received any investigational medication, including investigational vaccines, in the 3 months prior to baseline or is in the follow-up period of another clinical trial at the time of screening for this trial.
• Has a current or past clinically significant condition, which renders the subject unsuitable for the trial according to the investigator's judgement.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1, Cohort A; A single dose inhaled dose of 6 mg GH001 administered via a proprietary aerosol delivery device in eight subjects.	Drug: 5 Methoxy N,N Dimethyltryptamine; GH001 administered via inhalation; Other Names: Mebufotenin, 5-MeO-DMT, GH001
Experimental: Part 1, Cohort B; A single dose inhaled dose of 12 mg GH001 administered via a proprietary aerosol delivery device in eight subjects.	Drug: 5 Methoxy N,N Dimethyltryptamine; GH001 administered via inhalation; Other Names: Mebufotenin, 5-MeO-DMT, GH001
Experimental: Part 1, Cohort C; A single dose inhaled dose of 18 mg GH001 administered via a proprietary aerosol delivery device in eight subjects.	Drug: 5 Methoxy N,N Dimethyltryptamine; GH001 administered via inhalation; Other Names: Mebufotenin, 5-MeO-DMT, GH001
Experimental: Part 1, Cohort D (optional); A single inhaled intermediate dose of 8, 9, 10, 14, 15, or 16 mg GH001 administered via a proprietary aerosol delivery device in eight subjects (optional cohort dependent on study safety group [SSG] review of PK, PD and safety data from Cohorts A, B, and C).	Drug: 5 Methoxy N,N Dimethyltryptamine; GH001 administered via inhalation; Other Names: Mebufotenin, 5-MeO-DMT, GH001
Experimental: Part 1, Cohort E (optional); A single inhaled intermediate dose of 8, 9, 10, 14, 15, or 16 mg GH001 administered via a proprietary aerosol delivery device in eight subjects (optional cohort dependent on SSG review of PK, PD and safety data from Cohorts A, B, and C).	Drug: 5 Methoxy N,N Dimethyltryptamine; GH001 administered via inhalation; Other Names: Mebufotenin, 5-MeO-DMT, GH001
Experimental: Part 2, Cohort F; Up to three escalating inhaled doses of GH001 (doses as determined by Part 1, maximum single inhaled dose of 18 mg) administered via a proprietary aerosol delivery device in 12 subjects.	Drug: 5 Methoxy N,N Dimethyltryptamine; GH001 administered via inhalation; Other Names: Mebufotenin, 5-MeO-DMT, GH001

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: GH Research Ireland Limited

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2024
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: June 28, 2024
• First Submitted That Met QC Criteria: July 15, 2024
• First Posted (Actual): July 22, 2024

Study Record Updates

• Last Update Posted (Actual): August 7, 2024
• Last Update Submitted That Met QC Criteria: August 6, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Healthy volunteers; Pharmacokinetics; 5-MeO-DMT; 5-methoxy-N,N-dimethyltryptamine; Mebufotenin; GH001
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Agents; Serotonin Receptor Agonists; Serotonin Antagonists; Hallucinogens; N,N-Dimethyltryptamine
• Other Study ID Numbers: GH001-HV-106-2; IRAS Number (Other Identifier: 1009720)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No