Pharmacokinetics of GH001 in Healthy Volunteers

GH Research Ireland Limited46 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Healthy Volunteers

Interventions

5 Methoxy N,N DimethyltryptamineDRUG

GH001 administered via inhalation

PlaceboDRUG

GH001 Placebo administered via inhalation

Eligibility

Sex: ALLMin age: 18 YearsMax age: 64 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

GH Research Clinical Trial Site

Groningen, Netherlands

Outcomes

Primary Outcomes

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.

Time frame: up to 4 hours

Secondary Outcomes

Safety: Adverse Event (AE) reporting

Adverse events reported in the study and coded by MedDRA.

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: Up to 7 days

Safety: Frequency of clinically significant changes from baseline in Peak Flow Respirometry

Data from ClinicalTrials.gov

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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).

Time frame: 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)

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Up to 7 days