The primary objectives of this trial are to determine the pharmacokinetic (PK) profile and the safety and tolerability of GH001 delivered via a proprietary aerosol delivery device in healthy subjects after single-dose administration and a single-day individualized dosing regimen (IDR). As secondary objectives, the mebufotenin PK/ pharmacodynamic (PD) relationship, the PD profile of GH001 as evaluated by its psychoactive effects (PsE), the impact on cognitive performance, and the TCmax/2 and TCmax/10 (time taken for Cmax to decrease by 50 and 90%, respectively) are also assessed.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
52
GH001 administered via inhalation
GH Research Clinical Trial Site
London, United Kingdom
RECRUITINGSerum PK parameters of mebufotenin - maximum observed concentration (Cmax)
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.
Time frame: Up to 6 hours
Serum PK parameters of mebufotenin - time of maximum observed concentration (Tmax)
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.
Time frame: Up to 6 hours
Serum PK parameters of mebufotenin - terminal elimination half-life (t1/2)
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.
Time frame: Up to 6 hours
Serum PK parameters of mebufotenin - area under the serum concentration-time curve from time zero to the last quantifiable concentration (AUC0-t)
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.
Time frame: Up to 6 hours
Serum PK parameters of mebufotenin - area under the serum concentration-time curve extrapolated to infinity (AUC0-∞)
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.
Time frame: Up to 6 hours
Serum PK parameters of mebufotenin - terminal elimination rate constant (λz)
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.
Time frame: Up to 6 hours
Serum PK parameters of mebufotenin - apparent total body clearance (CL/F)
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.
Time frame: Up to 6 hours
Serum PK parameters of mebufotenin - apparent steady-state volume of distribution (VSS/F)
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.
Time frame: Up to 6 hours
Serum PK parameters of mebufotenin - Cmax/AUC0-∞
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.
Time frame: Up to 6 hours
Safety and tolerability: incidence of treatment-emergent adverse events
Adverse events reported in the study and coded by MedDRA.
Time frame: Up to 7 days
Safety and tolerability: clinically significant changes from baseline in electrocardiogram (ECG), vital signs, spirometry and safety laboratory assessments
Percentage of subjects with clinically significant changes\* from baseline in ECG (heart rate, RR, QT, PR, and QRS intervals, and QTcF). Percentage of subjects with clinically significant changes\* from baseline in vital signs (systolic and diastolic blood pressure, respiration rate, heart rate, peripheral oxygen saturation, body temperature). Percentage of subjects with clinically significant changes\* from baseline in spirometry (forced expiratory volume in 1 second \[FEV1\] and forced vital capacity \[FVC\]). Percentage of subjects with clinically significant changes\* from baseline in safety laboratory assessments (hematology, biochemistry, and urinalysis). \*Clinically significant changes as determined by the principal investigator
Time frame: Up to 7 days
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
The MOAA/S will be completed before and after GH001 dosing. Scored from 0 (deep sedation) to 5 (alert).
Time frame: Postdose, up to discharge on dosing day (Day 0)
Safety and tolerability: change from baseline in 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: From baseline up to 7 days
Safety and tolerability: assessment of subject discharge readiness at discharge on Day 0
Assessment of Discharge Readiness on the administration day by the principal investigator, using the Clinical Assessment of Discharge Readiness (CADR).
Time frame: Postdose, at discharge on dosing day (Day 0)
Safety and tolerability: Columbia-Suicide Severity Rating Scale (C-SSRS) categorization.
A detailed questionnaire assessing both suicidal behaviour and suicidal ideation.
Time frame: Up to 7 days
Safety and tolerability: Change from baseline in 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 and a higher score means a worse outcome.
Time frame: From baseline up to 7 days
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