■由于它们对情绪和幸福感的潜在影响,人们对诸如N,N-二甲基色胺(DMT)治疗重度抑郁症(MDD)。
■本研究A部分的目的是评估安全性,耐受性,在迷幻药初治的健康参与者中递增剂量的SPL026(DMT富马酸酯)的药代动力学(PK)和药效学(PD)曲线,以确定在随后的试验2a期部分(B部分:本手稿中未介绍)中对MDD患者的给药剂量。
■在第一阶段,随机,双盲,安慰剂对照,平行组,单剂量递增试验,未服用迷幻剂的参与者被随机分配至安慰剂组(n=8)或4种不同的递增剂量[9,12,17和21.5mg静脉注射(IV)]的SPL026(每剂n=6),以及2名治疗小组成员的心理支持.PK和急性(用药经验后立即)心理测量[包括神秘经验问卷(MEQ),自我溶解库存(EDI),并确定强度等级视觉模拟量表(IRVAS)]。其他终点测量为从基线到第8、15、30和90天的长期变化。这些措施包括沃里克和爱丁堡的心理健康量表以及斯皮尔伯格的状态特质焦虑清单。
■SPL026耐受性良好,具有可接受的安全性,无严重不良事件。有一些证据表明,最大血浆浓度与IRVAS升高之间存在相关性,MEQ,和EDI分数。这些趋势可能需要在更大的样本量中进行确认。通过对安全性的分析,耐受性,PD,PK结果,21.5毫克SPL026的剂量最有可能提供强烈的,容忍的经验。
■根据从该部分试验中获得的数据,在B部分中选择21.5mgSPL026作为2期IV输注10分钟的剂量(6mg/5分钟和15.5mg/5分钟)作为患者的剂量(将在未来的手稿中呈现).临床试验注册:www。clinicaltrials.gov,标识符NCT04673383;https://www.临床试验登记。欧盟,标识符2020-000251-13;https://www.isrctn.com/,标识符ISRCTN63465876。
UNASSIGNED: Due to their potential impact on mood and wellbeing there has been increasing interest in the potential of serotonergic psychedelics such as N,N-dimethyltryptamine (DMT) in the treatment of major depressive disorder (MDD).
UNASSIGNED: The aim of Part A of this
study was to evaluate the safety, tolerability, pharmacokinetics (PK) and
pharmacodynamic (PD) profile of escalating doses of SPL026 (DMT fumarate) in psychedelic-naïve healthy participants to determine a dose for administration to patients with MDD in the subsequent Phase 2a part of the
trial (Part B: not presented in this manuscript).
UNASSIGNED: In the Phase 1, randomized, double-blind, placebo-controlled, parallel-group, single dose-escalation
trial, psychedelic-naïve participants were randomized to placebo (n = 8) or four different escalating doses [9, 12, 17 and 21.5 mg intravenously (IV)] of SPL026 (n = 6 for each dose) together with psychological support from 2 therapy team members. PK and acute (immediately following dosing experience) psychometric measures [including mystical experience questionnaire (MEQ), ego dissolution inventory (EDI), and intensity rating visual analogue scale (IRVAS)] were determined. Additional endpoints were measured as longer-term change from baseline to days 8, 15, 30 and 90. These measures included the Warwick and Edinburgh mental wellbeing scale and Spielberger\'s state-trait anxiety inventory.
UNASSIGNED: SPL026 was well tolerated, with an acceptable safety profile, with no serious adverse events. There was some evidence of a correlation between maximum plasma concentration and increased IRVAS, MEQ, and EDI scores. These trends are likely to require confirmation in a larger sample size. Using the analysis of the safety, tolerability, PD, PK results, doses of 21.5 mg SPL026 were the most likely to provide an intense, tolerated experience.
UNASSIGNED: Based on the data obtained from this part of the
trial, a dose of 21.5 mg SPL026 given as a 2-phase IV infusion over 10 min (6 mg/5 min and 15.5 mg/5 min) was selected as the dose to be taken into patients in Part B (to be presented in a future manuscript).Clinical trial registration:www.clinicaltrials.gov, identifier NCT04673383; https://www.clinicaltrialsregister.eu, identifier 2020-000251-13; https://www.isrctn.com/, identifier ISRCTN63465876.