Phase 1 and 2 studies of sublingual dexmedetomidine, an alpha 2 adrenergic agonist, for treating opioid withdrawal
舌下含服右美托咪定(一种 α2 肾上腺素能激动剂)用于治疗阿片类药物戒断的 1 期和 2 期研究
基本信息
- 批准号:10478324
- 负责人:
- 金额:$ 331.22万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-08-01 至 2024-07-31
- 项目状态:已结题
- 来源:
- 关键词:Adrenergic AgonistsAdverse effectsAffinityAgitationAnxietyBindingBiological AssayBlood PressureBradycardiaBuprenorphineBypassClinicalDataDevelopmentDexmedetomidineDoseDouble-Blind MethodDropoutDropsDrug Metabolic DetoxicationEffectivenessExhibitsFentanylFilmFutureHeart RateHumanHypertensionHypotensionInpatientsLiverMeasuresMetabolismMonitorNaltrexoneOpiate AddictionOpioidOpioid agonistOutpatientsParticipantPatient Self-ReportPatientsPharmaceutical PreparationsPhasePhase II/III TrialPhysical DependencePlacebo ControlPlacebosPlayPublic HealthRandomizedReceptors, Adrenergic, alpha-2RespirationRoleSafetySedation procedureSerious Adverse EventSigns and SymptomsSiteSleepSleep disturbancesSuboxoneSubstance Withdrawal SyndromeSymptomsTestingTimeUnited States Food and Drug AdministrationUnited States National Institutes of HealthWithdrawalWithdrawal Symptomabuse liabilityassociated symptomclinically significantcompare effectivenesscravingdesignefficacy studyheroin useillicit drug useimprovedinnovationlofexidinenon-opioid analgesicopioid epidemicopioid overdoseopioid taperingopioid useopioid use disorderopioid withdrawaloverdose deathphase III trialplacebo controlled studyprimary endpointresponsesafety testingsecondary endpointside effectsuccesssynthetic opioid
项目摘要
Project Summary
The current epidemic of Opioid Use Disorder (OUD) is a severe public health crisis in the US, and in response,
the National Institutes of Health (NIH) is supporting development of innovative medications for treating OUD.
The withdrawal symptoms associated with cessation of opioid use are serious obstacles to initiating opioid
blockers (naltrexone) and may pose difficulties in transitioning patients to other medications for treating opioid
use disorder (MOUD), such as buprenorphine. The FDA approval of the alpha-2-adrenergic agonist lofexidine
has made a significant contribution to ameliorating OUD withdrawal, but only 40% of subjects became opioid
free in a pivotal study. This study was conducted prior to the widespread availability of the potent synthetic
opioid fentanyl, so the effectiveness of lofexidine in treating opioid withdrawal in fentanyl-dependent patients is
unclear. BioXcel has developed another alpha-2-adrenergic agonist dexmedetomidine as a sublingual (SL) film
(BXCL501). BXCL501 is potentially superior to alternatives such as opioid tapering because it is a non-opioid
with minimal abuse potential, and at doses that reduce opioid withdrawal symptoms, it has minimal adverse effects
on respiration, hypotension, hypertension, bradycardia, and sedation. Furthermore, it avoids potential liver
complications due to bypassing first-pass metabolism. Data collected during a recently completed multiple
ascending dose safety and preliminary efficacy study showed that the highest dose of BXCL501 tested
reduced anxiety and improved sleep disturbances, which are symptoms that are typically not well treated with
lofexidine. In the proposed studies, BXCL501 will be tested for its ability to decrease the signs and symptoms
of opioid withdrawal across multiple sites through two Specific Aims: 1 (UG3). A Phase 1b randomized, double-
blind, placebo-controlled safety, optimal dose finding, and preliminary efficacy inpatient study (n=160), and 2
(UH3). A Phase 2b randomized, double-blind, placebo-controlled outpatient study comparing the safety and
efficacy of BXCL501 to placebo and lofexidine (n=300). Two Go/No-Go criteria for moving from the UG3 to the
UH3 phases are: 1) BXCL501 is shown to reduce withdrawal symptoms (total SOWS score) more than 30%
compared to the SOWS score of subjects receiving placebo. 2) No more than one serious adverse event
attributed to BXCL501 among the subjects receiving active BXCL at the minimum dose identified to exhibit at
least a 30% reduction in withdrawal symptoms. Our positive clinical findings with BXCL501 and strong
investigative team promise high success for bringing this new treatment to market.
项目概要
当前阿片类药物使用障碍 (OUD) 的流行是美国一场严重的公共卫生危机,为应对这一问题,
美国国立卫生研究院 (NIH) 正在支持开发治疗 OUD 的创新药物。
与停止使用阿片类药物相关的戒断症状是开始使用阿片类药物的严重障碍
阻滞剂(纳曲酮),可能会给患者过渡到其他药物治疗阿片类药物带来困难
使用障碍(MOUD),例如丁丙诺啡。 FDA批准α-2-肾上腺素能激动剂洛非西定
对改善 OUD 戒断做出了重大贡献,但只有 40% 的受试者使用阿片类药物
免费进行一项关键研究。这项研究是在有效的合成药物广泛使用之前进行的
阿片类药物芬太尼,因此洛非西定治疗芬太尼依赖患者阿片类药物戒断的有效性是
不清楚。 BioXcel 开发了另一种 α-2-肾上腺素能激动剂右美托咪定作为舌下 (SL) 薄膜
(BXCL501)。 BXCL501 可能优于阿片类药物逐渐减少等替代品,因为它是一种非阿片类药物
滥用可能性最小,并且在减少阿片类药物戒断症状的剂量下,其副作用也最小
关于呼吸、低血压、高血压、心动过缓和镇静。此外,它还避免了潜在的肝脏
由于绕过首过代谢而引起的并发症。最近完成的多次收集的数据
递增剂量安全性和初步疗效研究表明,BXCL501测试的最高剂量
减少焦虑并改善睡眠障碍,这些症状通常无法通过以下方法得到很好的治疗
洛非西定。在拟议的研究中,将测试 BXCL501 减少体征和症状的能力
通过两个具体目标在多个地点减少阿片类药物戒断:1 (UG3)。 A 1b 期随机、双
盲法、安慰剂对照安全性、最佳剂量寻找和初步疗效住院研究 (n=160),以及 2
(呃3)。一项 2b 期随机、双盲、安慰剂对照门诊研究,比较安全性和
BXCL501 相对于安慰剂和洛非西丁的疗效 (n=300)。从 UG3 转移到 UG3 的两个通过/不通过标准
UH3 阶段是:1) BXCL501 显示可减少戒断症状(总 SOWS 评分)30% 以上
与接受安慰剂的受试者的 SOWS 评分进行比较。 2) 不超过1次严重不良事件
归因于接受活性 BXCL 的受试者中的 BXCL501,该受试者以最小剂量确定表现出
戒断症状至少减少 30%。我们对 BXCL501 的积极临床发现和强大的
研究团队承诺将这种新疗法推向市场将取得巨大成功。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
SANDRA D COMER其他文献
SANDRA D COMER的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('SANDRA D COMER', 18)}}的其他基金
Transcutaneous Phrenic Nerve Stimulation for Treating Opioid Overdose
经皮膈神经刺激治疗阿片类药物过量
- 批准号:
10681111 - 财政年份:2023
- 资助金额:
$ 331.22万 - 项目类别:
Development of a monoclonal antibody to reverse overdose from fentanyl and its analogs: from manufacturing to clinical trials
开发逆转芬太尼及其类似物过量的单克隆抗体:从制造到临床试验
- 批准号:
10615519 - 财政年份:2022
- 资助金额:
$ 331.22万 - 项目类别:
Development of ITI-333, a μ-opioid Receptor Partial Agonist and 5HT2A and D1 Receptor Antagonist, for the Treatment of Opioid Use Disorders
开发 ITI-333,一种 μ-阿片受体部分激动剂和 5HT2A 和 D1 受体拮抗剂,用于治疗阿片类药物使用障碍
- 批准号:
9841388 - 财政年份:2019
- 资助金额:
$ 331.22万 - 项目类别:
Phase 1a/1b Clinical Trials of Multivalent Opioid Vaccine Components
多价阿片类疫苗成分的 1a/1b 期临床试验
- 批准号:
10782616 - 财政年份:2018
- 资助金额:
$ 331.22万 - 项目类别:
CERC-501 Kappa Antagonist for Nicotine Dependence
CERC-501 尼古丁依赖性 Kappa 拮抗剂
- 批准号:
9041849 - 财政年份:2016
- 资助金额:
$ 331.22万 - 项目类别:
Dynamic Contrast-Enhanced MRI to Measure Blood-Brain Barrier Permeability in Substance Abusers
动态对比增强 MRI 测量药物滥用者的血脑屏障渗透性
- 批准号:
9066619 - 财政年份:2015
- 资助金额:
$ 331.22万 - 项目类别:
Dynamic Contrast-Enhanced MRI to Measure Blood-Brain Barrier Permeability in Substance Abusers
动态对比增强 MRI 测量药物滥用者的血脑屏障渗透性
- 批准号:
8989439 - 财政年份:2015
- 资助金额:
$ 331.22万 - 项目类别:
Risk and Benefits of Overdose Education and Naloxone Prescribing to Heroin Users
过量教育和向海洛因使用者开纳洛酮处方的风险和益处
- 批准号:
8694865 - 财政年份:2014
- 资助金额:
$ 331.22万 - 项目类别:
Risk and Benefits of Overdose Education and Naloxone Prescribing to Heroin Users
过量教育和向海洛因使用者开纳洛酮处方的风险和益处
- 批准号:
9330829 - 财政年份:2014
- 资助金额:
$ 331.22万 - 项目类别:
相似海外基金
Unraveling Adverse Effects of Checkpoint Inhibitors Using iPSC-derived Cardiac Organoids
使用 iPSC 衍生的心脏类器官揭示检查点抑制剂的副作用
- 批准号:
10591918 - 财政年份:2023
- 资助金额:
$ 331.22万 - 项目类别:
Optimization of mRNA-LNP vaccine for attenuating adverse effects and analysis of mechanism behind adverse effects
mRNA-LNP疫苗减轻不良反应的优化及不良反应机制分析
- 批准号:
23K15383 - 财政年份:2023
- 资助金额:
$ 331.22万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of adverse effects of combined exposure to low-dose chemicals in the living environment on allergic diseases and attempts to reduce allergy
阐明生活环境中低剂量化学品联合暴露对过敏性疾病的不良影响并尝试减少过敏
- 批准号:
23H03556 - 财政年份:2023
- 资助金额:
$ 331.22万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Green tea-based nano-enhancer as an adjuvant for amplified efficacy and reduced adverse effects in anti-angiogenic drug treatments
基于绿茶的纳米增强剂作为抗血管生成药物治疗中增强疗效并减少不良反应的佐剂
- 批准号:
23K17212 - 财政年份:2023
- 资助金额:
$ 331.22万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Effects of Tobacco Heating System on the male reproductive function and towards to the reduce of the adverse effects.
烟草加热系统对男性生殖功能的影响以及减少不利影响。
- 批准号:
22H03519 - 财政年份:2022
- 资助金额:
$ 331.22万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Mitigating the Adverse Effects of Ultrafines in Pressure Filtration of Oil Sands Tailings
减轻油砂尾矿压力过滤中超细粉的不利影响
- 批准号:
563657-2021 - 财政年份:2022
- 资助金额:
$ 331.22万 - 项目类别:
Alliance Grants
1/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
1/4-破译ECT结果和不良反应的机制(DECODE)
- 批准号:
10521849 - 财政年份:2022
- 资助金额:
$ 331.22万 - 项目类别:
4/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
4/4-破译ECT结果和不良反应的机制(DECODE)
- 批准号:
10671022 - 财政年份:2022
- 资助金额:
$ 331.22万 - 项目类别:
2/4 Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)
2/4 ECT 结果和不良反应的破译机制(DECODE)
- 批准号:
10670918 - 财政年份:2022
- 资助金额:
$ 331.22万 - 项目类别:
Downsides of downhill: The adverse effects of head vibration associated with downhill mountain biking on visuomotor and cognitive function
速降的缺点:与速降山地自行车相关的头部振动对视觉运动和认知功能的不利影响
- 批准号:
2706416 - 财政年份:2022
- 资助金额:
$ 331.22万 - 项目类别:
Studentship