An Open-label Phase 1 Trial to Determine the Pharmacokinetics, Pharmacodynamics, and Safety of GH001 Administered Via a Proprietary Aerosol Delivery Device in Healthy Subjects
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- GH Research Ireland Limited
- Enrollment
- 52
- Locations
- 1
- Primary Endpoint
- Serum PK parameters of mebufotenin - time of maximum observed concentration (Tmax)
Study Overview
Brief Summary
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 Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 64 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Body mass index (BMI) in the range of 18.5 to 35 kg/m2 (inclusive) at screening
- •Good mental health in the opinion of the investigator.
- •Normal spirometry (FEV1 of >80% of predicted and FVC of >80% of predicted value) at screening.
Exclusion Criteria
- •Has known allergies or hypersensitivity or any other contraindication to mebufotenin, bufotenin, melatonin or triptans.
- •Has received any investigational medication, including investigational vaccines, in the 3 months prior to baseline or is in the follow-up period of another clinical trial at the time of screening for this trial.
- •Has a current or past clinically significant condition, which renders the subject unsuitable for the trial according to the investigator's judgement.
Arms & Interventions
Part 1, Cohort A
A single dose inhaled dose of 6 mg GH001 administered via a proprietary aerosol delivery device in eight subjects.
Intervention: 5 Methoxy N,N Dimethyltryptamine (Drug)
Part 1, Cohort B
A single dose inhaled dose of 12 mg GH001 administered via a proprietary aerosol delivery device in eight subjects.
Intervention: 5 Methoxy N,N Dimethyltryptamine (Drug)
Part 1, Cohort C
A single dose inhaled dose of 18 mg GH001 administered via a proprietary aerosol delivery device in eight subjects.
Intervention: 5 Methoxy N,N Dimethyltryptamine (Drug)
Part 1, Cohort D (optional)
A single inhaled intermediate dose of 8, 9, 10, 14, 15, or 16 mg GH001 administered via a proprietary aerosol delivery device in eight subjects (optional cohort dependent on study safety group [SSG] review of PK, PD and safety data from Cohorts A, B, and C).
Intervention: 5 Methoxy N,N Dimethyltryptamine (Drug)
Part 1, Cohort E (optional)
A single inhaled intermediate dose of 8, 9, 10, 14, 15, or 16 mg GH001 administered via a proprietary aerosol delivery device in eight subjects (optional cohort dependent on SSG review of PK, PD and safety data from Cohorts A, B, and C).
Intervention: 5 Methoxy N,N Dimethyltryptamine (Drug)
Part 2, Cohort F
Up to three escalating inhaled doses of GH001 (doses as determined by Part 1, maximum single inhaled dose of 18 mg) administered via a proprietary aerosol delivery device in 12 subjects.
Intervention: 5 Methoxy N,N Dimethyltryptamine (Drug)
Outcomes
Primary Outcomes
Serum PK parameters of mebufotenin - time of maximum observed concentration (Tmax)
Time Frame: Up to 6 hours
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.
Serum PK parameters of mebufotenin - terminal elimination half-life (t1/2)
Time Frame: Up to 6 hours
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.
Serum PK parameters of mebufotenin - apparent total body clearance (CL/F)
Time Frame: Up to 6 hours
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.
Serum PK parameters of mebufotenin - maximum observed concentration (Cmax)
Time Frame: Up to 6 hours
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.
Serum PK parameters of mebufotenin - terminal elimination rate constant (λz)
Time Frame: Up to 6 hours
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.
Serum PK parameters of mebufotenin - apparent steady-state volume of distribution (VSS/F)
Time Frame: Up to 6 hours
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.
Serum PK parameters of mebufotenin - area under the serum concentration-time curve from time zero to the last quantifiable concentration (AUC0-t)
Time Frame: Up to 6 hours
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.
Safety and tolerability: Change from baseline in Brief Psychiatric Rating Scale (BPRS).
Time Frame: From baseline 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 and a higher score means a worse outcome.
Serum PK parameters of mebufotenin - area under the serum concentration-time curve extrapolated to infinity (AUC0-∞)
Time Frame: Up to 6 hours
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.
Serum PK parameters of mebufotenin - Cmax/AUC0-∞
Time Frame: Up to 6 hours
For PK analyses, blood samples will be collected before and up to 6 hours after the administration of GH001 to determine mebufotenin serum concentrations.
Safety and tolerability: clinically significant changes from baseline in electrocardiogram (ECG), vital signs, spirometry and safety laboratory assessments
Time Frame: Up to 7 days
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
Safety and tolerability: Columbia-Suicide Severity Rating Scale (C-SSRS) categorization.
Time Frame: Up to 7 days
A detailed questionnaire assessing both suicidal behaviour and suicidal ideation.
Safety and tolerability: incidence of treatment-emergent adverse events
Time Frame: Up to 7 days
Adverse events reported in the study and coded by MedDRA.
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
Time Frame: Postdose, up to discharge on dosing day (Day 0)
The MOAA/S will be completed before and after GH001 dosing. Scored from 0 (deep sedation) to 5 (alert).
Safety and tolerability: change from baseline in Clinician Administered Dissociative States Scale (CADSS)
Time Frame: From baseline 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.
Safety and tolerability: assessment of subject discharge readiness at discharge on Day 0
Time Frame: Postdose, at discharge on dosing day (Day 0)
Assessment of Discharge Readiness on the administration day by the principal investigator, using the Clinical Assessment of Discharge Readiness (CADR).
Secondary Outcomes
No secondary outcomes reported