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

NCT06511947 | Recruiting Phase 1

• 2 other identifiers: GH001-HV-106-2IRAS Number
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Healthy Volunteers

Keywords

Mebufotenin; 5-MeO-DMT; 5-methoxy-N,N-dimethyltryptamine; GH001; Healthy volunteers; Pharmacokinetics

Outcome Measures

Primary Outcomes (16)

• 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

Study Arms (6)

Part 1, Cohort A

EXPERIMENTAL

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

Part 1, Cohort B

EXPERIMENTAL

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

Part 1, Cohort C

EXPERIMENTAL

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

Part 1, Cohort D (optional)

EXPERIMENTAL

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

Part 1, Cohort E (optional)

EXPERIMENTAL

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

Part 2, Cohort F

EXPERIMENTAL

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

Interventions

5 Methoxy N,N Dimethyltryptamine DRUG

GH001 administered via inhalation

Also known as: Mebufotenin, 5-MeO-DMT, GH001

Part 1, Cohort A; Part 1, Cohort B; Part 1, Cohort C; Part 1, Cohort D (optional); Part 1, Cohort E (optional); Part 2, Cohort F

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GH Research Ireland Limited: lead

Study Sites (1)

GH Research Clinical Trial Site

London, United Kingdom

RECRUITING

MeSH Terms

Interventions

Methoxydimethyltryptamines

Intervention Hierarchy (Ancestors)

N,N-Dimethyltryptamine; Tryptamines; Biogenic Monoamines; Biogenic Amines; Amines; Organic Chemicals; Bufotenin; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Serotonin

Central Study Contacts

GH Research Limited Clinical Trial Enquiries

CONTACT

+353 87 450 3237; clinicaltrials@ghres.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study will include separate single- and multiple-dose parts. Part 1 (Single-Dose Part): An open-label, non-randomized, parallel design where subjects will be assigned to receive single doses of GH001 delivered via a proprietary aerosol delivery device on a single day in three consecutive cohorts (Cohorts A, B, and C) with eight subjects per cohort. Up to two additional cohorts (Cohorts D and E) may be added before Part 2 is initiated. Part 2 (Multiple-Dose Part): An open-label, non-randomized design where up to three escalating doses of GH001 will be administered to subjects via a proprietary aerosol delivery device on a single day in one cohort of 12 subjects (Cohort F).

Study Record Dates

• First Submitted: June 28, 2024
• First Posted: July 22, 2024
• Study Start: August 1, 2024
• Primary Completion: February 1, 2025
• Study Completion: February 1, 2025
• Last Updated: August 7, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)