Safety and Pharmacokinetics of GH002 in Healthy Volunteers
- Conditions
- Healthy Volunteers
- Interventions
- Drug: Placebo
- Registration Number
- NCT05753956
- Lead Sponsor
- GH Research Ireland Limited
- Brief Summary
The primary objectives of this study are to investigate the safety and serum pharmacokinetics of 5-MeO-DMT in healthy volunteers in a double-blind, placebo-controlled, randomized study design with single, injected doses of GH002 and in an open-label, non-randomized study design with intra-subject dose-escalation of GH002. As secondary objectives, the PK/ pharmacodynamic relationship, PD profile of GH002 as evaluated by its psychoactive effects and impact on cognitive performance, and the serum PK of the metabolite bufotenine are also assessed.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 64
- Has a body mass index (BMI) in the range of 18.5 and 35 kg/m2 (inclusive) at Screening.
- Is deemed in good physical health by the investigator.
- Is in good mental health in the opinion of the investigator and clinical psychologist
- Has known allergies or hypersensitivity or any other contra-indication to 5-MeO-DMT.
- Has received any investigational medication, including investigational vaccines, within the 6 weeks prior to baseline
- Has a current or past clinically significant condition, which renders the subject unsuitable for the trial according to the Investigator's judgement.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort B: Dose B single dose 5 Methoxy N,N Dimethyltryptamine A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects) Cohort E: Dose E single dose 5 Methoxy N,N Dimethyltryptamine A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects) Cohort G: Dose G single dose 5 Methoxy N,N Dimethyltryptamine A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects) Cohort J: Individualized Dosing Regimen 5 Methoxy N,N Dimethyltryptamine Administration of up to 3 doses of GH002 within a single day (doses to be confirmed following review of data from single-dose part) Cohort A: Dose A single dose 5 Methoxy N,N Dimethyltryptamine A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects) Cohort B: Dose B single dose Placebo A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects) Cohort D: Dose D single dose Placebo A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects) Cohort C: Dose C single dose 5 Methoxy N,N Dimethyltryptamine A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects) Cohort C: Dose C single dose Placebo A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects) Cohort F: Dose F single dose Placebo A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects) Cohort F: Dose F single dose 5 Methoxy N,N Dimethyltryptamine A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects) Cohort A: Dose A single dose Placebo A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects) Cohort D: Dose D single dose 5 Methoxy N,N Dimethyltryptamine A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects) Cohort E: Dose E single dose Placebo A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects) Cohort G: Dose G single dose Placebo A single dose of GH002 or placebo administered by i.v. bolus injection (randomized as 6 active and 2 placebo subjects)
- Primary Outcome Measures
Name Time Method The pharmacokinetic (PK) parameters derived from laboratory assay results of the systemic levels of 5-MeO-DMT Up to 6 hours For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH002 to determine 5-MeO-DMT serum concentrations.
Safety and tolerability: local tolerance (injection site reactions) Up to discharge on dosing day Local infusion site findings will be assessed as none, mild, moderate and severe for the following signs and symptoms of the applicable site: dryness, redness, swelling, pain, tenderness, and itching and other.
Safety and tolerability: Assessment of subject-discharge readiness at discharge on Day 0 Up to discharge on dosing day Assessment of Discharge Readiness on the administration day by the Principal Investigator, using the Clinical Assessment of Discharge Readiness (CADR).
Safety and tolerability: incidence of treatment emergent adverse events Up to 7 days Adverse events reported in the study and coded by MedDRA.
Safety and tolerability: Clinically significant changes from baseline in ECG, vital signs and safety laboratory assessments Up to 7 days Clinically significant changes in ECG include any significant change in rate or rhythm as determined by the principal investigator
Safety and tolerability: Assessment of sedation (Modified Observer's Assessment of Alertness and Sedation [MOAA/S]) following each dose and as part of the discharge evaluation on Day 0 Up to discharge on dosing day The Modified Observer's Assessment of Alertness and Sedation scale (MOAA/S) will be completed before and after GH002 dosing. Scored from 0 (deep sedation) to 5 (alert)
Safety and tolerability: Columbia-Suicide Severity Rating Scale (C-SSRS) categorization based on the Columbia Classification Algorithm of Suicide Assessment (C-CASA). Up to 7 days A detailed questionnaire assessing both suicidal behaviour and suicidal ideation.
Safety and tolerability: Change from baseline in Brief Psychiatric Rating Scale (BPRS). Up to 7 days 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.
Safety and tolerability: Change from baseline in Clinician Administered Dissociative States Scale (CADSS) Up to 7 days 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
- Secondary Outcome Measures
Name Time Method Pharmacodynamic assessment: The dose-related psychoactive effects of GH002 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
PK/PD relationship(s) of 5-MeO-DMT Up to 1 hour after dosing In particular the correlation between Cmax and AUC with PES score and duration of PsE as scored by the investigator will be described
Pharmacodynamic assessment: Challenging Experiences Questionnaire (CEQ) Up to 1 hour after dosing Completed by the subject after GH002 administration and assesses seven factors (grief, fear, death, insanity, isolation, physical distress, and paranoia) all scored from 0 to 5.
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: 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 Verbal recognition memory (VRM) test Up to 7 days The VRM test is based on successive auditory presentations of 18-word lists followed by attempted recall.
Cognitive Function: Change from baseline in Rapid visual information processing (RVP) test Up to 7 days A computerized test assessing the reaction time in response to a visual stimulus.
The pharmacokinetic (PK) parameters derived from laboratory assay results of the systemic levels of bufotenine Up to 6 hours For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH002 to determine bufotenine serum concentrations.
Cognitive Function: Change from baseline in Spatial Working Memory (SWM) task Up to 7 days The SWM test requires retention and manipulation of visuospatial information. This test has notable executive function demands, and measures strategy use as well as errors. In this task the subject has to search for tokens hidden in boxes on screen. The subject must touch a box to open the box to reveal either a yellow token or an empty box. Once the subject has found a yellow token, they must touch the outline of the right-hand side of the screen to 'store' it. The subject must then continue searching through the boxes until all of the tokens have been found. The test takes about 4 minutes to complete
Cognitive Function: Change from baseline in Digit Symbol Substitution Task (DSST) Up to 7 days The DSST is a global measure of cognitive ability, requiring the engagement of multiple cognitive domains in order to complete effectively. A computerized test with the task is to match digits with symbols from encoding list. The number of digits correctly encoded within 90 seconds is the performance measure.
Trial Locations
- Locations (1)
GH Research Clinical Trial Site
🇳🇱Groningen, Netherlands