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
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 52
- 试验地点
- 1
- 主要终点
- Serum PK parameters of mebufotenin - terminal elimination half-life (t1/2)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Part 1, Cohort A
A single dose inhaled dose of 6 mg GH001 administered via a proprietary aerosol delivery device in eight subjects.
干预措施: 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.
干预措施: 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.
干预措施: 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).
干预措施: 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).
干预措施: 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.
干预措施: 5 Methoxy N,N Dimethyltryptamine (Drug)
结局指标
主要结局
Serum PK parameters of mebufotenin - terminal elimination half-life (t1/2)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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)
时间窗: 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).
时间窗: 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-∞)
时间窗: 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-∞
时间窗: 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
时间窗: 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.
时间窗: Up to 7 days
A detailed questionnaire assessing both suicidal behaviour and suicidal ideation.
Safety and tolerability: incidence of treatment-emergent adverse events
时间窗: 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
时间窗: 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)
时间窗: 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
时间窗: 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).
次要结局
未报告次要终点