Pharmacokinetics of GH001 in Healthy Volunteers
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
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|
Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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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:
Drug: Placebo
GH001 Placebo administered via inhalation
Other Names:
|
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:
Drug: Placebo
GH001 Placebo administered via inhalation
Other Names:
|
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:
Drug: Placebo
GH001 Placebo administered via inhalation
Other Names:
|
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:
|
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:
|
Outcome Measures
Primary Outcome Measures
- The pharmacokinetic (PK) parameters derived from laboratory assay results of the systemic levels of 5-MeO-DMT and bufotenine [up to 4 hours]
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.
Secondary Outcome Measures
- Safety: Adverse Event (AE) reporting [Up to 30 days]
Adverse events reported in the study and coded by MedDRA.
- Safety: Frequency of clinically significant changes from baseline in electrocardiogram (ECG) recording [Up to 7 days]
Clinically significant changes in ECG include any significant change in rate or rhythm as determined by the principal investigator
- Safety: Frequency of clinically significant changes from baseline in vital signs measurement [Up to 7 days]
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
- Safety: Frequency of clinically significant changes from baseline in safety laboratory tests of blood and urine [Up to 7 days]
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.
- Safety: Frequency of clinically significant changes from baseline in Peak Flow Respirometry [1 hour after dosing]
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).
- Safety: Frequency of clinically significant changes from baseline in level of sedation [30 minutes and 1 hour after dosing]
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)
- Safety: Change from baseline in Clinician Administered Dissociative States Scale (CADSS) [Up to 30 days]
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.
- Safety: Assessment of Subject-Discharge readiness [up to 3 hours after last study drug administration]
Assessment of Discharge Readiness on the administration day by the Principal Investigator, using the Clinical Global Assessment of Discharge Readiness (CGADR).
- Mental Health: Change from baseline in Brief Psychiatric Rating Scale (BPRS) [Up to 30 days]
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.
- Mental Health: Change from baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) [Up to 30 days]
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.
- Pharmacodynamic assessment: The dose-related psychoactive effects of GH001 as evaluated by a Visual Analogue Scale [up to 1 hour after dosing]
The Peak Experience Scale (PES) is a Visual Analogue Scale scored from 0-100
- Pharmacodynamic assessment: 30-Question Mystical Experience Questionnaire (MEQ30) [up to 1 hour after dosing]
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.
- Pharmacodynamic assessment: Challenging Experiences Questionnaire (CEQ) [up to 1 hour after dosing]
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.
- Pharmacodynamic assessment: Duration of the psychoactive effects (PsE) [up to 1 hour after dosing]
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.
- Cognitive Function: Change from baseline in Psychomotor Vigilance Task (PVT) [Up to 7 days]
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).
- Cognitive Function: Change from baseline in Auditory Verbal Learning Test (AVLT) [Up to 7 days]
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.
- Cognitive Function: Change from baseline in Spatial Working Memory (SWM) task [Up to 7 days]
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.
- Cognitive Function: Change from baseline in Digit Symbol Substitution Task (DSST) [Up to 7 days]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Subject has a body mass index (BMI) in the range of 18.5 and 35.0 kg/m2 (inclusive);
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Subject is in good physical health in the opinion of the principal investigator (PI);
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Subject is in good mental health in the opinion of the PI and clinical psychologist;
Exclusion Criteria:
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Has known allergies or hypersensitivity or any other contraindication to 5-MeO-DMT;
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Has received any investigational medication within the last 4 weeks;
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Has a medical condition, which renders the subject unsuitable for the study.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | GH Research Clinical Trial Site | Groningen | Netherlands |
Sponsors and Collaborators
- GH Research Ireland Limited
Investigators
- Study Director: GH Research Clinical Team, GH Research Ireland Limited
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- GH001-HV-103
- 2021-000241-40