Development of cannabinoid-opioid combination with opioid sparing and synergistic analgesic effects to prevent opioid use disorder and overdose.
开发具有阿片类药物节约和协同镇痛作用的大麻素-阿片类药物组合,以防止阿片类药物使用障碍和过量。
基本信息
- 批准号:10391263
- 负责人:
- 金额:$ 97.39万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-30 至 2023-08-31
- 项目状态:已结题
- 来源:
- 关键词:Absence of pain sensationAccountingAddressAdvanced DevelopmentAgonistAmericanAnalgesicsAnti Inflammatory AnalgesicsAnxietyAreaAttenuatedBiological AssayBuprenorphineCannabidiolCannabinoidsCannabis sativa plantCaregiversChronic low back painClinicalClinical ResearchClinical TrialsDataDependenceDevelopmentDoseDrug InteractionsDrug KineticsExhibitsFDA approvedFentanylFormulationGastaut syndromeGoalsGrantHalf-LifeHelping to End Addiction Long-termHeroinHumanIndividualLegal patentLicensingManufactured SuppliesMeasuresMental DepressionOpiate AddictionOpioidOpioid AnalgesicsOverdosePatientsPharmaceutical PreparationsPharmacologic SubstancePhasePhysical DependencePhysiciansPreventionPublic HealthRegimenRegulatory PathwayReportingResearch SupportRiskRodentRodent ModelRoleSafetySecureSeizuresSmall Business Innovation Research GrantSocietiesSublingual drug administrationTechnologyTherapeuticTimeToxicologyTuberous sclerosis protein complexUnited States National Institutes of HealthVentilatory DepressionWithdrawalWithdrawal Symptomaddictionanalytical methodchronic paindravet syndromehealinghigh riskimprovedlead candidatemedication safetymeetingsmethod developmentnovelnovel therapeuticsopioid abuseopioid abuse preventionopioid epidemicopioid misuseopioid overdoseopioid sparingopioid therapyopioid useopioid use disorderopioid withdrawaloverdose deathphytocannabinoidpre-clinicalpreclinical studyprescription opioidprescription opioid misusepreventproduct developmentprototypesafety studysedativestability testing
项目摘要
Project Summary/Abstract
More than 1.6 million individuals in the US meet criteria for an opioid use disorder, with millions
more reporting use or misuse of opioid pain relievers in the past month. Along with an increase in
opioid use disorders, a rise in opioid-related overdose deaths has occurred in the last decade.
Chronic pain and opioid abuse are more prevalent than before constituting a public health crisis
and exacting a heavy toll on patients, caregivers, physicians, and society. There is a current
therapeutic challenge for managing opioid use, opioid withdrawal symptoms, chronic pain, and/or
associated anxiety and depression. A severe need remains for alternative and safe therapeutic
regimens that properly treat these conditions. We propose to develop a cannabinoid-opioid
combination with opioid-sparing and synergistic analgesic effects to prevent opioid use disorder
and overdose, addressing the current national opioid epidemic. BDH Pharma, LLC completed a
proof-of-concept preclinical study of a fixed dose cannabinoid-opioid combination that
demonstrated opioid-sparing and synergistic analgesic effects, with the combination providing
greater analgesia in a rodent model of chronic pain than a standard dose of the opioid alone.
Building on that data, our SBIR Phase I grant supported a preclinical pharmacokinetic drug-drug
interaction and safety study to determine if co-administration altered the pharmacokinetics and/or
respiratory depression related to either compound in rodents. Study results indicated PK
parameters remained unaltered, except for a decrease in half-life for the opioid. When measuring
respiratory depression, we found that the presence of the cannabinoid was able to attenuate
respiratory depression induced by the opioid. Taken together, study results have shown that our
lead candidate, BDH-001, exhibits synergistic and opioid-sparing analgesic effects and does not
display significant drug-drug interactions nor has any deleterious effects on respiratory
depression. This suggests that BDH-001 may have improved analgesia with lower opioid doses
and thereby lower the risk of dependence, withdrawal, diversion, abuse, and overdose. This
proposal will continue the development of BDH-001 by completing pre-formulation and
formulation studies to support co-formulation of our FDC for sublingual administration and provide
required data for IND submission. These studies will support the selection of prototypes for short-
term stability testing before the clinical supply manufacturing under GMP conditions and long-
term stability testing. Upon completion of the proposed Phase II aims and subsequent IND
submission, BDH-001 will be ready for the clinical phase of development with an initial indication
of chronic low back pain.
项目摘要/摘要
在美国,超过160万人符合阿片类药物使用障碍的标准,其中数百万人
在过去的一个月里,有更多的报告使用或误用阿片类止痛药。同时还增加了
在阿片类药物使用障碍方面,与阿片类药物有关的过量死亡在过去十年中有所上升。
慢性疼痛和阿片类药物滥用比构成公共健康危机之前更加普遍
并给患者、照顾者、医生和社会带来沉重的代价。有一股水流
管理阿片类药物使用、阿片类药物戒断症状、慢性疼痛和/或
相关的焦虑和抑郁。仍然迫切需要替代和安全的治疗方法
恰当地治疗这些疾病的养生法。我们建议开发一种大麻类阿片类药物
联合阿片类药物节制和协同止痛预防阿片类药物使用障碍
和过量,解决了目前全国范围内的阿片类药物流行问题。BDH Pharma,LLC完成了一项
一种固定剂量大麻素-阿片类药物组合的概念验证临床前研究
展示了阿片类药物的节制和协同止痛效果,联合提供了
在慢性疼痛的啮齿动物模型中,比标准剂量的阿片类药物单独使用有更好的止痛效果。
在这些数据的基础上,我们的SBIR第一阶段资助支持了临床前药代动力学药物-药物
相互作用和安全性研究,以确定联合给药是否改变了药代动力学和/或
与啮齿动物体内的任何一种化合物有关的呼吸抑制。研究结果表明PK
参数保持不变,除了阿片类药物的半衰期减少。当测量时
呼吸抑制,我们发现大麻素的存在能够减弱
阿片类药物引起的呼吸抑制。总而言之,研究结果表明,我们的
主要候选药物BDH-001显示出协同和非阿片类药物的止痛作用,而不是
显示出显著的药物相互作用,对呼吸道也没有任何有害影响
抑郁症。这表明Bdh-001可能在较低的阿片类药物剂量下改善了止痛效果。
从而降低依赖、戒断、转移注意力、滥用和过量服药的风险。这
建议书将继续开发BDH-001,完成预制和
配方研究,以支持我们的FDC的共同配方,以进行语下管理,并提供
提交IND所需的数据。简而言之,这些研究将支持原型的选择-
GMP条件下临床制剂生产前的长期稳定性试验
术语稳定性测试。在完成拟议的第二阶段目标和随后的IND
提交,Bdh-001将准备好进入临床开发阶段,并有初步的适应症
慢性腰背痛。
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)
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Marisa Briones其他文献
Marisa Briones的其他文献
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{{ truncateString('Marisa Briones', 18)}}的其他基金
Development of cannabinoid-opioid combination with opioid sparing and synergistic analgesic effects to prevent opioid use disorder and overdose.
开发具有阿片类药物节约和协同镇痛作用的大麻素-阿片类药物组合,以防止阿片类药物使用障碍和过量。
- 批准号:
9912141 - 财政年份:2019
- 资助金额:
$ 97.39万 - 项目类别:
Development of cannabinoid-opioid combination with opioid sparing and synergistic analgesic effects to prevent opioid use disorder and overdose.
开发具有阿片类药物节约和协同镇痛作用的大麻素-阿片类药物组合,以防止阿片类药物使用障碍和过量。
- 批准号:
10118287 - 财政年份:2019
- 资助金额:
$ 97.39万 - 项目类别:
Investigating the Role of HIV-1 Integrase in the Uncoating of the Viral Core
研究 HIV-1 整合酶在病毒核心脱壳中的作用
- 批准号:
7798575 - 财政年份:2008
- 资助金额:
$ 97.39万 - 项目类别:
Investigating the Role of HIV-1 Integrase in the Uncoating of the Viral Core
研究 HIV-1 整合酶在病毒核心脱壳中的作用
- 批准号:
7788868 - 财政年份:2008
- 资助金额:
$ 97.39万 - 项目类别:
Investigating the Role of HIV-1 Integrase in the Uncoating of the Viral Core
研究 HIV-1 整合酶在病毒核心脱壳中的作用
- 批准号:
7404900 - 财政年份:2008
- 资助金额:
$ 97.39万 - 项目类别:
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