Safety and Pharmacokinetics of GH002 in Healthy Volunteers

NCT05753956 | Completed Phase 1

• 2 other identifiers: GH002-HV-1052022-002620-13
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objectives of this study are to investigate the safety and serum pharmacokinetics of 5-MeO-DMT in healthy volunteers in a double-blind, placebo-controlled, randomized study design with single, injected doses of GH002 and in an open-label, non-randomized study design with intra-subject dose-escalation of GH002. As secondary objectives, the PK/ pharmacodynamic relationship, PD profile of GH002 as evaluated by its psychoactive effects and impact on cognitive performance, and the serum PK of the metabolite bufotenine are also assessed.

Conditions

Healthy Volunteers

Keywords

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

Outcome Measures

Primary Outcomes (9)

• 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: local tolerance (injection site reactions)

  Local infusion site findings will be assessed as none, mild, moderate and severe for the following signs and symptoms of the applicable site: dryness, redness, swelling, pain, tenderness, and itching and other.

  Up to discharge on dosing day

• Safety and tolerability: Clinically significant changes from baseline in ECG, vital signs and safety laboratory assessments

  Clinically significant changes in ECG include any significant change in rate or rhythm 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 Modified Observer's Assessment of Alertness and Sedation scale (MOAA/S) will be completed before and after GH002 dosing. Scored from 0 (deep sedation) to 5 (alert)

  Up to discharge on dosing day

• 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

  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).

  Up to discharge on dosing day

• Safety and tolerability: Columbia-Suicide Severity Rating Scale (C-SSRS) categorization based on the Columbia Classification Algorithm of Suicide Assessment (C-CASA).

  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.

  Up to 7 days

• The pharmacokinetic (PK) parameters derived from laboratory assay results of the systemic levels of 5-MeO-DMT

  For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH002 to determine 5-MeO-DMT serum concentrations.

  Up to 6 hours

Secondary Outcomes (10)

• Pharmacodynamic assessment: The dose-related psychoactive effects of GH002 as evaluated by a Visual Analogue Scale

  Up to 1 hour after dosing

• Pharmacodynamic assessment: Challenging Experiences Questionnaire (CEQ)

  Up to 1 hour after dosing

• Pharmacodynamic assessment: 30-Question Mystical Experience Questionnaire (MEQ30)

  Up to 1 hour after dosing

• Pharmacodynamic assessment: Duration of the psychoactive effects (PsE)

  Up to 1 hour after dosing

• PK/PD relationship(s) of 5-MeO-DMT

  Up to 1 hour after dosing

Study Arms (8)

Cohort A: Dose A single dose

EXPERIMENTAL

A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects)

Drug: 5 Methoxy N,N Dimethyltryptamine; Drug: Placebo

Cohort B: Dose B single dose

EXPERIMENTAL

A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects)

Drug: 5 Methoxy N,N Dimethyltryptamine; Drug: Placebo

Cohort C: Dose C single dose

EXPERIMENTAL

A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects)

Drug: 5 Methoxy N,N Dimethyltryptamine; Drug: Placebo

Cohort D: Dose D single dose

EXPERIMENTAL

A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects)

Drug: 5 Methoxy N,N Dimethyltryptamine; Drug: Placebo

Cohort E: Dose E single dose

EXPERIMENTAL

A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects)

Drug: 5 Methoxy N,N Dimethyltryptamine; Drug: Placebo

Cohort F: Dose F single dose

EXPERIMENTAL

A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects)

Drug: 5 Methoxy N,N Dimethyltryptamine; Drug: Placebo

Cohort G: Dose G single dose

EXPERIMENTAL

A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects)

Drug: 5 Methoxy N,N Dimethyltryptamine; Drug: Placebo

Cohort J: Individualized Dosing Regimen

EXPERIMENTAL

Administration of up to 3 doses of GH002 within a single day (doses to be confirmed following review of data from single-dose part)

Drug: 5 Methoxy N,N Dimethyltryptamine

Interventions

5 Methoxy N,N Dimethyltryptamine DRUG

GH002 administered via i.v. bolus injection(s)

Also known as: GH002, 5-MeO-DMT

Cohort A: Dose A single dose; Cohort B: Dose B single dose; Cohort C: Dose C single dose; Cohort D: Dose D single dose; Cohort E: Dose E single dose; Cohort F: Dose F single dose; Cohort G: Dose G single dose; Cohort J: Individualized Dosing Regimen

Placebo DRUG

GH002 placebo administered via i.v. bolus injection

Also known as: GH002 placebo

Cohort A: Dose A single dose; Cohort B: Dose B single dose; Cohort C: Dose C single dose; Cohort D: Dose D single dose; Cohort E: Dose E single dose; Cohort F: Dose F single dose; Cohort G: Dose G single dose

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Has a body mass index (BMI) in the range of 18.5 and 35 kg/m2 (inclusive) at Screening.
• Is deemed in good physical health by the investigator.
• Is in good mental health in the opinion of the investigator and clinical psychologist

You may not qualify if:

• Has known allergies or hypersensitivity or any other contra-indication to 5-MeO-DMT.
• Has received any investigational medication, including investigational vaccines, within the 6 weeks prior to baseline
• 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

Groningen, Netherlands

Location

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This study will include separate single and multiple-dose parts. Single-dose Part: A double-blind, placebo-controlled, randomized, dose escalation design with single doses of GH002 delivered by i.v. bolus injection in 7 consecutive cohorts with 8 subjects per cohort (randomized as 6 active and 2 placebo): Cohort A: Dose A Cohort B: Dose B Cohort C: Dose C Cohort D: Dose D Cohort E: Dose E Cohort F: Dose F Cohort G: Dose G Up to 2 additional cohorts may be added before the IDR part is initiated. These will be named cohorts H and I, if needed. Multiple-Dose Part: An open-label, non-randomized design with up to 3 doses of GH002 administered to subjects by i.v. bolus injection(s) on a single day in one cohort of 8 subjects: Cohort J: Individualized Dosing Regimen with GH002. The exact doses of study drug to be administered will be determined after an unblinded review of the safety, PK and PD data from all of the cohorts in the single dose part of the trial

Study Record Dates

• First Submitted: February 23, 2023
• First Posted: March 3, 2023
• Study Start: December 22, 2022
• Primary Completion: November 29, 2023
• Study Completion: November 29, 2023
• Last Updated: January 25, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)