Pharmacokinetics of GH001 in Healthy Volunteers

DMT

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.

Intervention / Treatment

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
  • 5 Methoxy N,N Dimethyltryptamine (DRUG)
    GH001 administered via inhalation
  • Placebo (DRUG)
    GH001 Placebo administered via inhalation

Condition or Disease

  • Healthy Volunteers

Phase

  • Phase 1

    • Study Design

    Study type: INTERVENTIONAL
    Status: Completed
    Study results: No Results Available
    Age: 18 Years to 64 Years
    Enrollment: 46 (ACTUAL)
    Funded by: Industry
    Allocation: Randomized
    Primary Purpose: Treatment

    Masking

    TRIPLE:
    • Participant
    • Investigator
    • Outcomes Assessor

    Clinical Trial Dates

    Start date: Jun 21, 2021 ACTUAL
    Primary Completion: Oct 23, 2021 ACTUAL
    Completion Date: Nov 22, 2021 ACTUAL
    Study First Posted: Dec 20, 2021 ACTUAL
    Last Updated: Dec 13, 2021

    Sponsors / Collaborators

    Lead Sponsor: N/A
    Lead sponsor is responsible party
    Responsible Party: N/A

    Location

    Groningen, Netherlands

    Participant Groups

    • A single, inhaled dose of GH001 6 mg or placebo (randomized as 8 active and 2 placebo subjects)

    • A single, inhaled dose of GH001 12 mg or placebo (randomized as 8 active and 2 placebo subjects)

    • A single, inhaled dose of GH001 18 mg or placebo (randomized as 8 active and 2 placebo subjects)

    • 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)

    • 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)

    Eligibility Criteria

    Sex: All
    Minimum Age: 18
    Maximum Age: 64
    Age Groups: Adult
    Healthy Volunteers: Yes

    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.

    Primary Outcomes

    • 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 Outcomes

    • Adverse events reported in the study and coded by MedDRA.

    • Clinically significant changes in ECG include any significant change in rate or rhythm as determined by the principal investigator

    • 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 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.

    • 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).

    • 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)

    • 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.

    • Assessment of Discharge Readiness on the administration day by the Principal Investigator, using the Clinical Global Assessment of Discharge Readiness (CGADR).

    • 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.

    • 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.

    • The Peak Experience Scale (PES) is a Visual Analogue Scale scored from 0-100

    • 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.

    • 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.

    • 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.

    • 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).

    • 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.

    • 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.

    • 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.

    More Details

    NCT Number: NCT05163691
    Other IDs: GH001-HV-103
    Study URL: https://clinicaltrials.gov/study/NCT05163691
    Last updated: Sep 29, 2023