Development of microparticle-based topical treatments for treating erectile dysfunction in patients refractory to oral PDE5 inhibitors
开发基于微粒的局部治疗方法,用于治疗口服 PDE5 抑制剂难治性患者的勃起功能障碍
基本信息
- 批准号:10258888
- 负责人:
- 金额:$ 69.72万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-07-19 至 2023-06-30
- 项目状态:已结题
- 来源:
- 关键词:AlprostadilAnimal ModelAnimalsBackBack TraumaBindingCaviaClinical ResearchClinical TrialsConsultDataDermalDevelopmentDiagnosisDoseErectile dysfunctionFDA approvedFeedbackFormulationFutureGoalsGrantHumanImpairmentInjectionsMalignant NeoplasmsMaximum Tolerated DoseMiniature SwineNerveNerve EndingsNitric OxideOperative Surgical ProceduresOralOryctolagus cuniculusPatientsPenile ProsthesisPersonal SatisfactionPharmaceutical PreparationsPhasePhase I Clinical TrialsPositioning AttributePreparationProductionQuality of lifeRadical ProstatectomyRattusRefractoryResearch DesignSuppositoriesSystemSystemic blood pressureTherapeuticTimeTopical applicationToxic effectToxicologyVacuum PumpsWorkalternative treatmentanalytical methodbasecompliance behaviordesignerectionexperiencefirst-in-humanin vivoinhibitor/antagonistirritationmanmeetingsmembermennerve damagenerve transectionneurotransmissionnovelnovel strategiespatient tolerabilitypenisphase 2 studyphosphodiesterase Vprogramsresponsesafety studysildenafilstandard carevirtual
项目摘要
Abstract
Following radical prostatectomy (RP), virtually all men experience erectile dysfunction (ED),
primarily due to damage to the cavernous nerve (CN). Yet, first-line treatments for ED, orally
administered phosphodiesterase 5 inhibitors (PDE5i), fail to elicit an erectile response for a
majority of patients suffering from ED as a result of RP (ED-RP). Alternative treatments are highly
invasive and/or have poor efficacy and are typically not even attempted. For a man who
experiences ED following RP, the trauma of back-to-back diagnoses (cancer and ED) has a
profound impact on quality-of-life, relationships, and well-being. There is, therefore, an urgent
need to find a novel approach to the treatment of ED in this patient group.
A primary factor in the development of ED-RP is that damage to the CN during RP impairs
neuronal signals that release sufficient NO from CN endings to initiate an erection. Thus,
formulations that increase local levels of NO may elicit an erectile response in the absence of
neuronal signals and may also enable cooperativity with PDE5i to enhance the erectile response.
This hypothesis was proven in Phase I where it was demonstrated that a novel transdermal
microparticle delivery system for NO (NO-MP) was able to elicit an erectile response when
administered alone or in combination with 1/10 the human equivalent dose of the leading PDE5i,
sildenafil. When NO-MP and sildenafil were used in combination, an improvement in the time for
onset of the first erectile response was observed, and the number of erections was greater than
treatment with NO-MP alone.
In Specific Aim 1 of Phase II, we will determine if the cooperativity in eliciting an erectile response
seen between NO-MP and sildenafil exists with other members of the FDA-approved PDE5i class.
This will confirm that the observation in Phase I is class-specific and will expand/define the
portfolio of potential commercial partners. In Specific Aim 2 we will initiate a GMP start-up program
at Zylö Therapeutics and confirm that a demonstration batch is as effective in eliciting an erectile
response as the small batch prep used in Specific Aim 1. Specific Aim 3 will establish the
maximum tolerated dose (MTD) in dose-range-finding studies conducted in rats and minipigs in
order to inform the design of later IND-enabling toxicology studies. In addition, a dermal sensitivity
study in guinea pigs and a dermal irritation study in rabbits will be conducted as part of the suite
of safety studies required by the FDA for topical products. Finally, in Specific Aim 4, a pre-IND
meeting will be held with the FDA to finalize remaining studies required for an IND application and
initiation of a Phase I clinical study.
At the conclusion of these phase II studies, we expect to have: (i) confirmed that NO-MP is
cooperative across the PDE5i class; (ii) generated a demonstration batch of NO-MP with
confirmed efficacy; (iii) conducted dermal toxicity studies to provide sensitivity and irritation data
and to establish the MTD; and (iv) consulted with the FDA regarding future development work
during a pre-IND meeting. Overall, we will be ready to initiate further toxicity studies in preparation
for an IND filing and a Phase I clinical trial.
摘要
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 }}
Andrew R Draganski其他文献
Andrew R Draganski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('Andrew R Draganski', 18)}}的其他基金
Development of an endocannabinoid microparticle formulation for the topical treatment of cutaneous manifestations of lupus erythematosus.
开发用于局部治疗红斑狼疮皮肤表现的内源性大麻素微粒制剂。
- 批准号:
10699531 - 财政年份:2023
- 资助金额:
$ 69.72万 - 项目类别:
Development and optimization of a nitric oxide releasing microparticle-basedtopical treatment for onychomycosis
基于一氧化氮释放微粒的甲癣局部治疗方法的开发和优化
- 批准号:
10686200 - 财政年份:2022
- 资助金额:
$ 69.72万 - 项目类别:
Optimization of a nanoparticle-based topical PDE5i formulation for treatment of erectile dysfunction
用于治疗勃起功能障碍的基于纳米颗粒的局部 PDE5i 制剂的优化
- 批准号:
10601895 - 财政年份:2022
- 资助金额:
$ 69.72万 - 项目类别:
Development and optimization of a nitric oxide releasing microparticle-basedtopical treatment for onychomycosis
基于一氧化氮释放微粒的甲癣局部治疗方法的开发和优化
- 批准号:
10547384 - 财政年份:2022
- 资助金额:
$ 69.72万 - 项目类别:
Development of microparticle-based topical treatments for treating erectile dysfunction in patients refractory to oral PDE5 inhibitors
开发基于微粒的局部治疗方法,用于治疗口服 PDE5 抑制剂难治性患者的勃起功能障碍
- 批准号:
10453581 - 财政年份:2021
- 资助金额:
$ 69.72万 - 项目类别:
相似海外基金
Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
- 批准号:
495434 - 财政年份:2023
- 资助金额:
$ 69.72万 - 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
- 批准号:
10642519 - 财政年份:2023
- 资助金额:
$ 69.72万 - 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
- 批准号:
10586596 - 财政年份:2023
- 资助金额:
$ 69.72万 - 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
- 批准号:
10590479 - 财政年份:2023
- 资助金额:
$ 69.72万 - 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
- 批准号:
23K06011 - 财政年份:2023
- 资助金额:
$ 69.72万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
- 批准号:
10682117 - 财政年份:2023
- 资助金额:
$ 69.72万 - 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
- 批准号:
10708517 - 财政年份:2023
- 资助金额:
$ 69.72万 - 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
- 批准号:
10575566 - 财政年份:2023
- 资助金额:
$ 69.72万 - 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
- 批准号:
23K15696 - 财政年份:2023
- 资助金额:
$ 69.72万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
- 批准号:
23K15867 - 财政年份:2023
- 资助金额:
$ 69.72万 - 项目类别:
Grant-in-Aid for Early-Career Scientists














{{item.name}}会员




