Pharmacokinetics of GH001 in Healthy Volunteers

A Phase 1 Study to Determine the Pharmacokinetics and Pharmacodynamics of Single and Multiple Inhaled Doses of GH001 in Healthy Volunteers

The primary objective of this study is to investigate the serum pharmacokinetics of 5-MeO-DMT and its metabolite, bufotenine in healthy volunteers in a double-blind, placebo-controlled, randomized study design with single, inhaled doses of GH001 and in an open-label, non-randomized study design with intra-subject dose-escalation of GH001. As a secondary objective, the safety and tolerability of GH001, the mental health and well-being of the subjects after GH001 dosing(s), the pharmacodynamic profile of GH001 as evaluated by its psychoactive effects, and cognitive measures are also assessed.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: 5 Methoxy N,N Dimethyltryptamine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 1

Contacts and Locations

Study Locations

• Netherlands
  • Groningen, Netherlands
    • GH Research Clinical Trial Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject has a body mass index (BMI) in the range of 18.5 and 35.0 kg/m2 (inclusive);
• Subject is in good physical health in the opinion of the principal investigator (PI);
• Subject is in good mental health in the opinion of the PI and clinical psychologist;

Exclusion Criteria:

• Has known allergies or hypersensitivity or any other contraindication to 5-MeO-DMT;
• Has received any investigational medication within the last 4 weeks;
• Has a medical condition, which renders the subject unsuitable for the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A - 6 mg single-dose; A single, inhaled dose of GH001 6 mg or placebo (randomized as 8 active and 2 placebo subjects)	Drug: 5 Methoxy N,N Dimethyltryptamine; GH001 administered via inhalation; Other Names: GH001; 5-MeO-DMT; Drug: Placebo; GH001 Placebo administered via inhalation; Other Names: GH001 Placebo
Experimental: Group B - 12 mg single-dose; A single, inhaled dose of GH001 12 mg or placebo (randomized as 8 active and 2 placebo subjects)	Drug: 5 Methoxy N,N Dimethyltryptamine; GH001 administered via inhalation; Other Names: GH001; 5-MeO-DMT; Drug: Placebo; GH001 Placebo administered via inhalation; Other Names: GH001 Placebo
Experimental: Group C - 18 mg single-dose; A single, inhaled dose of GH001 18 mg or placebo (randomized as 8 active and 2 placebo subjects)	Drug: 5 Methoxy N,N Dimethyltryptamine; GH001 administered via inhalation; Other Names: GH001; 5-MeO-DMT; Drug: Placebo; GH001 Placebo administered via inhalation; Other Names: GH001 Placebo
Experimental: Group D - Individualized Dosing Regimen, 1-hour interval; Administration of up to 3 inhaled doses of GH001 within a single day (6 mg, followed by 12 mg, followed by 18 mg) with a 1-hour dose interval (8 subjects)	Drug: 5 Methoxy N,N Dimethyltryptamine; GH001 administered via inhalation; Other Names: GH001; 5-MeO-DMT
Experimental: Group E - Individualized Dosing Regimen, 2-hour interval; Administration of up to 3 inhaled doses of GH001 within a single day (6 mg, followed by 12 mg, followed by 18 mg) with a 2-hour dose interval (8 subjects)	Drug: 5 Methoxy N,N Dimethyltryptamine; GH001 administered via inhalation; Other Names: GH001; 5-MeO-DMT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The pharmacokinetic (PK) parameters derived from laboratory assay results of the systemic levels of 5-MeO-DMT and bufotenine	For PK analyses, blood samples will be collected before and up to 4 hours after the administration of GH001 to determine 5-MeO-DMT and bufotenine serum concentrations.	up to 4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety: Adverse Event (AE) reporting	Adverse events reported in the study and coded by MedDRA.	Up to 30 days
Safety: Frequency of clinically significant changes from baseline in electrocardiogram (ECG) recording	Clinically significant changes in ECG include any significant change in rate or rhythm as determined by the principal investigator	Up to 7 days
Safety: Frequency of clinically significant changes from baseline in vital signs measurement	Vital signs include heart rate (beats per minute), blood pressure (mmHg), respiratory rate (breaths per minute), oxygen saturation (%), and temperature (degrees celsius). Changes are defined as any clinically significant change from baseline as determined by the principal investigator	Up to 7 days
Safety: Frequency of clinically significant changes from baseline in safety laboratory tests of blood and urine	Safety laboratory analyses are analyses of blood samples (biochemistry, hematology) and urine samples (urinalysis). Changes are defined as any clinically significant change from baseline as determined by the principal investigator.	Up to 7 days
Safety: Frequency of clinically significant changes from baseline in Peak Flow Respirometry	Peak Flow is assessed using a standard peak flow respirometer, with the assessment done three times and the best of the three scores recorded as the final score (liters/minute).	1 hour after dosing
Safety: Frequency of clinically significant changes from baseline in level of sedation	The Modified Observer's Assessment of Alertness and Sedation scale (MOAA/S) will be completed before and after GH001 dosing. Scored from 0 (deep sedation) to 5 (alert)	30 minutes and 1 hour after dosing
Safety: Change from baseline in Clinician Administered Dissociative States Scale (CADSS)	Change from baseline in the 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 30 days
Safety: Assessment of Subject-Discharge readiness	Assessment of Discharge Readiness on the administration day by the Principal Investigator, using the Clinical Global Assessment of Discharge Readiness (CGADR).	up to 3 hours after last study drug administration
Mental Health: Change from baseline in Brief Psychiatric Rating Scale (BPRS)	Change from baseline in the 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 30 days
Mental Health: Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)	Change from baseline in the Columbia-Suicide Severity Rating Scale (C-SSRS). A detailed questionnaire assessing both suicidal behaviour and suicidal ideation. No combined score is created.	Up to 30 days
Pharmacodynamic assessment: The dose-related psychoactive effects of GH001 as evaluated by a Visual Analogue Scale	The Peak Experience Scale (PES) is a Visual Analogue Scale scored from 0-100	up to 1 hour after dosing
Pharmacodynamic assessment: 30-Question Mystical Experience Questionnaire (MEQ30)	The MEQ30 is a validated procedure for assessing the extent of the psychoactive effects experienced by a subject. The validated MEQ30 uses thirty assessment questions across four areas of experience, all scored from 0 to 5.	up to 1 hour after dosing
Pharmacodynamic assessment: Challenging Experiences Questionnaire (CEQ)	Completed by the subject after GH001 administration and assesses seven factors (grief, fear, death, insanity, isolation, physical distress, and paranoia) all scored from 0 to 5.	up to 1 hour after dosing
Pharmacodynamic assessment: Duration of the psychoactive effects (PsE)	The duration of the experience, defined as time in minutes from drug administration to time when the subject reports that any psychoactive symptoms have subsided will be recorded.	up to 1 hour after dosing
Cognitive Function: Change from baseline in Psychomotor Vigilance Task (PVT)	Change from baseline in the Psychomotor Vigilance Test (PVT). A computerized test assessing the reaction time in response to a visual stimulus. Outcome measures are Response Time and the number of attentional lapses (Response Time ≥ 500 msec).	Up to 7 days
Cognitive Function: Change from baseline in Auditory Verbal Learning Test (AVLT)	The AVLT is one of the most widely used word learning tests in clinical research and practice. The test is based on successive auditory presentations of 15-word lists followed by attempted recall. The AVLT outcome measures are the rate of learning as well as the level of recall.	Up to 7 days
Cognitive Function: Change from baseline in Spatial Working Memory (SWM) task	The SWM task requires retention and manipulation of visuo-spatial information. This self-ordered test provides a measure of strategy as well as working memory errors. The test involves a number of colored squares (boxes) shown on the screen which require a selection strategy to fill an empty column. The test takes about 4 minutes to complete. Outcome measures of the SWM include errors and strategy. The computerized Corsi Block will be the version of the SWM task used in this study.	Up to 7 days
Cognitive Function: Change from baseline in Digit Symbol Substitution Task (DSST)	Change from baseline in the Digit Symbol Substitution Test (DSST). A computerized test with the task is to match digits with symbols from encoding list. The number of digits correctly encoded within 3 minutes is the performance measure.	Up to 7 days

Collaborators and Investigators

• Sponsor: GH Research Ireland Limited
• Investigators: Study Director: GH Research Clinical Team, GH Research Ireland Limited

Publications and helpful links

Helpful Links

• GH Research Company Website

Study record dates

Study Major Dates

• Study Start (Actual): June 21, 2021
• Primary Completion (Actual): October 23, 2021
• Study Completion (Actual): November 22, 2021

Study Registration Dates

• First Submitted: November 18, 2021
• First Submitted That Met QC Criteria: December 13, 2021
• First Posted (Actual): December 20, 2021

Study Record Updates

• Last Update Posted (Actual): December 20, 2021
• Last Update Submitted That Met QC Criteria: December 13, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Healthy Volunteers; 5-MeO-DMT; 5-methoxy-N,N-dimethyltryptamine; 5-methoxy-dimethyltryptamine
• 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-103; 2021-000241-40 (EudraCT Number)

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
• product manufactured in and exported from the U.S.: No