Pharmacokinetics of GH001 Delivered Via a Proprietary Aerosol Delivery Device in Healthy Subjects
- Registration Number
- NCT06511947
- Lead Sponsor
- GH Research Ireland Limited
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 52
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 1, Cohort E (optional) 5 Methoxy N,N Dimethyltryptamine 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). Part 2, Cohort F 5 Methoxy N,N Dimethyltryptamine 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. Part 1, Cohort A 5 Methoxy N,N Dimethyltryptamine A single dose inhaled dose of 6 mg GH001 administered via a proprietary aerosol delivery device in eight subjects. Part 1, Cohort C 5 Methoxy N,N Dimethyltryptamine A single dose inhaled dose of 18 mg GH001 administered via a proprietary aerosol delivery device in eight subjects. Part 1, Cohort D (optional) 5 Methoxy N,N Dimethyltryptamine 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). Part 1, Cohort B 5 Methoxy N,N Dimethyltryptamine A single dose inhaled dose of 12 mg GH001 administered via a proprietary aerosol delivery device in eight subjects.
- Primary Outcome Measures
Name Time Method Serum PK parameters of mebufotenin - time of maximum observed concentration (Tmax) 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) 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) 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) 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) 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) 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) 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). 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-∞) 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-∞ 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 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 investigatorSafety and tolerability: Columbia-Suicide Severity Rating Scale (C-SSRS) categorization. Up to 7 days A detailed questionnaire assessing both suicidal behaviour and suicidal ideation.
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: 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 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) 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 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 Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
GH Research Clinical Trial Site
🇬🇧London, United Kingdom