Pharmacokinetics of GH001 in Healthy Volunteers

Study Overview
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Brief Summary
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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.

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

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: 5 Methoxy N,N Dimethyltryptamine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This study will include separate single- and multiple-dose parts. Single-dose Part: A double-blind, placebo-controlled, randomized, parallel-group design with single, inhaled doses of GH001 in 3 groups of 10 subjects (randomized as 8 active and 2 placebo subjects per group): Group A: single inhaled dose of 6 mg GH001 Group B: single inhaled dose of 12 mg GH001 Group C: single inhaled dose of 18 mg GH001 Multiple-Dose Part: An open-label, non-randomized administration of up to 3 inhaled doses of GH001 within a single day (6 mg, followed by 12 mg, followed by 18 mg) with two different dose intervals (8 subjects per group): Group D: 1-hour interval Group E: 2-hour interval
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A - 6 mg single-dose<br>A single, inhaled dose of GH001 6 mg or placebo (randomized as 8 active and 2 placebo subjects) | Drug: 5 Methoxy N,N Dimethyltryptamine<br>* GH001 administered via inhalation<br>* Other names: 5-MeO-DMT;Drug: Placebo<br>* GH001 Placebo administered via inhalation<br>* Other names: GH001 Placebo;|
| Experimental: Group B - 12 mg single-dose<br>A single, inhaled dose of GH001 12 mg or placebo (randomized as 8 active and 2 placebo subjects) | Drug: 5 Methoxy N,N Dimethyltryptamine<br>* GH001 administered via inhalation<br>* Other names: 5-MeO-DMT;Drug: Placebo<br>* GH001 Placebo administered via inhalation<br>* Other names: GH001 Placebo;|
| Experimental: Group C - 18 mg single-dose<br>A single, inhaled dose of GH001 18 mg or placebo (randomized as 8 active and 2 placebo subjects) | Drug: 5 Methoxy N,N Dimethyltryptamine<br>* GH001 administered via inhalation<br>* Other names: 5-MeO-DMT;Drug: Placebo<br>* GH001 Placebo administered via inhalation<br>* Other names: GH001 Placebo;|
| Experimental: Group D - Individualized Dosing Regimen, 1-hour interval<br>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<br>* GH001 administered via inhalation<br>* Other names: 5-MeO-DMT;|
| Experimental: Group E - Individualized Dosing Regimen, 2-hour interval<br>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<br>* GH001 administered via inhalation<br>* Other names: 5-MeO-DMT;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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5-MeO-DMT, 5-methoxy-N,N-dimethyltryptamine, 5-methoxy-dimethyltryptamine, Healthy Volunteers, Pharmacokinetics