Healthy Volunteers
Conditions
Keywords
Mebufotenin, 5-MeO-DMT, 5-methoxy-N,N-dimethyltryptamine, GH001, Healthy volunteers, Pharmacokinetics
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.
Interventions
GH001 administered via inhalation
Sponsors
GH Research Ireland Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This study will include separate single- and multiple-dose parts. Part 1 (Single-Dose Part): An open-label, non-randomized, parallel design where subjects will be assigned to receive single doses of GH001 delivered via a proprietary aerosol delivery device on a single day in three consecutive cohorts (Cohorts A, B, and C) with eight subjects per cohort. Up to two additional cohorts (Cohorts D and E) may be added before Part 2 is initiated. Part 2 (Multiple-Dose Part): An open-label, non-randomized design where up to three escalating doses of GH001 will be administered to subjects via a proprietary aerosol delivery device on a single day in one cohort of 12 subjects (Cohort F).
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and tolerability: incidence of treatment-emergent adverse events | Up to 7 days | Adverse events reported in the study and coded by MedDRA. |
| 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 - 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 - 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. |
| 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 - 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 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 - 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 - 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 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 | 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). |
| Safety 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: 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. |
Countries
United Kingdom
Contacts
Primary ContactGH Research Limited Clinical Trial Enquiries
Outcome results
None listed