A Phase I, Randomised, Double-Blind, Placebo-Controlled Study to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Ascending Intravenous Doses of ELE-101 in Healthy Adult Participants (Part 1) and Part 2, Open-Label Study to Evaluate a Range of Pharmacodynamic Effects of a Single Intravenous Dose of ELE-101 in Patients With Major Depressive Disorder.
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 84
- 试验地点
- 1
- 主要终点
- Part 1: Percentage of participants with at least one safety event
研究概览
简要总结
A study to assess the safety and tolerability of a drug called ELE-101 and see how the body absorbs and removes the drug and how it affects the body in healthy adult participants (Part 1) and in patients with depression (Part 2).
详细描述
This is a 2-part study. Part 1 is a phase I, double-blind, placebo-controlled, randomized study to assess the safety, tolerability, pharmacokinetic (PK) profile, pharmacodynamic (PD) and subjective drug intensity (SDI) of single ascending intravenous (IV) doses of ELE-101 in healthy male and female adult participants. Part 2 is a Phase IIa, open-label study to evaluate a range of pharmacodynamic effects of a single intravenous dose of ELE-101 in patients with depression.
Healthy participants will receive either ELE-101 or placebo as an IV infusion in Part 1 and patients with MDD will receive ELE-101 as an IV infusion in Part 2.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Open label in Part 2
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy male or female participants aged 18 to 65 years, inclusive.
- •Participants have a body mass index (BMI) of 18 to 35 kg/m2, inclusive.
- •Participants are able and willing to give written informed consent, adhere to the compliance terms during participation in the study, undergo the examinations and testing set forth in the study Protocol and clearly and reliably communicate their subjective symptoms to the Investigator.
- •Part 2 Only: Patient has a diagnosis of MDD and is not on antidepressant medication.
排除标准
- •Current, or history (within the last 6 months) of, alcohol or substance use disorder.
- •Use of pharmacological compounds for psychiatric or neurological conditions acting on the CNS within 30 days or 5 half-lives (whichever is longer) prior to Screening.
- •Current or clinically relevant history of schizophrenia, psychotic, bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, borderline personality disorder or panic disorder.
- •In first-degree relatives, a history of schizophrenia, psychosis, bipolar disorder, delusional disorder, paranoid personality disorder or schizoaffective disorder.
- •History of a diagnosis of Hallucinogen Persistent Perceptual Disorder (HPPD).
- •Significant suicide risk.
- •Other personal circumstances and behavior that is incompatible with establishment of rapport or safe exposure to psilocin, as judged by the Investigator.
- •Part 1 Only: Ongoing current MDD, or history of MDD within the last year.
研究组 & 干预措施
Cohort 1 (Part 1)
A single 10-minute intravenous infusion of 0.25 mg ELE-101 or placebo (randomized as 6 active and 2 placebo)
干预措施: ELE-101 (Drug)
Cohort 1 (Part 1)
A single 10-minute intravenous infusion of 0.25 mg ELE-101 or placebo (randomized as 6 active and 2 placebo)
干预措施: ELE-101 Placebo (Drug)
Cohort 2 (Part 1)
A single 10-minute intravenous infusion of 0.75 mg ELE-101 or placebo (randomized as 6 active and 2 placebo)
干预措施: ELE-101 (Drug)
Cohort 2 (Part 1)
A single 10-minute intravenous infusion of 0.75 mg ELE-101 or placebo (randomized as 6 active and 2 placebo)
干预措施: ELE-101 Placebo (Drug)
Cohort 3 (Part 1)
A single 10-minute intravenous infusion of 2.0 mg ELE-101 or placebo (randomized as 6 active and 2 placebo)
干预措施: ELE-101 (Drug)
Cohort 3 (Part 1)
A single 10-minute intravenous infusion of 2.0 mg ELE-101 or placebo (randomized as 6 active and 2 placebo)
干预措施: ELE-101 Placebo (Drug)
Cohort 4 (Part 1)
A single TBD minute intravenous infusion of TBD mg ELE-101 or placebo (randomized as 6 active and 2 placebo)
干预措施: ELE-101 (Drug)
Cohort 4 (Part 1)
A single TBD minute intravenous infusion of TBD mg ELE-101 or placebo (randomized as 6 active and 2 placebo)
干预措施: ELE-101 Placebo (Drug)
Cohort 5 (Part 1)
A single TBD minute intravenous infusion of TBD mg ELE-101 or placebo (randomized as 6 active and 2 placebo)
干预措施: ELE-101 (Drug)
Cohort 5 (Part 1)
A single TBD minute intravenous infusion of TBD mg ELE-101 or placebo (randomized as 6 active and 2 placebo)
干预措施: ELE-101 Placebo (Drug)
Cohort 6 (Part 2)
A single TBD minute intravenous infusion of TBD mg ELE-101
干预措施: ELE-101 (Drug)
结局指标
主要结局
Part 1: Percentage of participants with at least one safety event
时间窗: Baseline up to Day 8
* Safety will be evaluated by the monitoring of adverse events (AEs), vital signs, blood pressure, heart rate, pulse oximetry, electrocardiogram (ECG) evaluations, clinical laboratory assessments, injection site reactions and physical examination findings. * Suicidal ideation and behavior will be evaluated using the Columbia-Suicide Severity Rating Scale (C-SSRS). * Percentage of participants who experience at least one treatment-emergent adverse event (TEAE) will be captured. * Tolerability will be measured using the SDI questionnaires to rate the intensity of the psychedelic experience alongside recordings of anticipated adverse effects such as nausea and headache.
Part 2: Subjective Drug Intensity Ratings
时间窗: pre-dose and at multiple time-points up to 24 hours post-dose
- The SDI questionnaire will be used to rate the real-time intensity of the psychedelic experience
次要结局
- Part 1 and 2: Cmax: Maximum observed plasma concentration for ELE-101 and its metabolites(pre-dose and at multiple time-points up to 24 hours post-dose)
- Part 1 and 2: Tmax: Time to reach maximum plasma concentration (Cmax) for ELE-101 and its metabolites(pre-dose and at multiple time-points up to 24 hours post-dose)
- Part 1 and 2: AUCinf: Area under the plasma concentration-time curve from Time 0 to Infinity for ELE-101 and its metabolites(pre-dose and at multiple time-points up to 24 hours post-dose)
- Part 1 and 2: AUClast: Area under the plasma concentration-time curve from Time 0 to the time of the last quantifiable concentration for ELE-101 and its metabolites(pre-dose and at multiple time-points up to 24 hours post-dose)
- Part 1 and 2: AUC0-24: Area under the plasma concentration-time curve from Time 0 to 24 hours for ELE-101 and its metabolites(pre-dose and at multiple time-points up to 24 hours post-dose)
- Part 1 and 2: VZ: volume of distribution during the terminal disposition phase for ELE-101 and its metabolites(pre-dose and at multiple time-points up to 24 hours post-dose)
- Part 1 and 2: VZss: volume of distribution at steady state for ELE-101 and its metabolites(pre-dose and at multiple time-points up to 24 hours post-dose)
- Part 1 and 2: Cl: apparent total clearance from plasma for ELE-101 and its metabolites(pre-dose and at multiple time-points up to 24 hours post-dose)
- Part 1 and 2: MRTinf: mean residence time from Time 0 to Infinity for ELE-101 and its metabolites(pre-dose and at multiple time-points up to 24 hours post-dose)
- Part 1 and 2: t1/2: Terminal disposition phase half-life for ELE-101 and its metabolites(pre-dose and at multiple time-points up to 24 hours post-dose)
- Part 1 and 2: Dischargeability: Assessment of subject-discharge readiness(post-dose and 24 hours post-dose)
- Part 1: The dose related psychoactive effects of ELE-101 as evaluated by a Visual Analogue Scale(pre-dose and at multiple time-points up to 24 hours post-dose)
- Part 2: The effects of ELE-101 on the severity of depression evaluated by the Montgomery-Asberg Depression Rating Scale (MADRS)(Baseline up to Day 85)
- Part 2: Percentage of participants with at least one safety event(Baseline up to Day 85)