Phase 1/2a, Open-Label, Dose-Escalation and Safety Study of APC-100 [Pentamethylchromanol, 2,2,5,7,8-Pentamethyl-6] in Men With Advanced Prostate Cancer

This study is a phase 1/2a, open label, dose escalation and safety study of APC-100 (2,2,5,7,8-Pentamethyl-6-chromanol) in men with advanced prostate cancer.

开始日期2011-08-01

申办/合作机构

DMK Pharmaceuticals Corp.

100 项与 APC-100 相关的临床结果

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100 项与 APC-100 相关的转化医学

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100 项与 APC-100 相关的专利（医药）

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项与 APC-100 相关的文献（医药）

2016-04-01·Investigational New Drugs3区 · 医学

A multicenter phase 1/2a dose-escalation study of the antioxidant moiety of vitamin E 2,2,5,7,8-pentamethyl-6-chromanol (APC-100) in men with advanced prostate cancer

3区 · 医学

Article

作者: Liu, Glenn ; Wilding, George ; Kyriakopoulos, Christos E ; Heath, Elisabeth I ; Yayehyirad, Mulusew ; Eickhoff, Jens C ; Kolesar, Jill ; Moll, Thomas

BACKGROUNDA phase 1/2a dose escalation study of APC-100 (2,2,5,7,8-Pentamethyl-6-chromanol) was conducted to determine maximum tolerated dose (MTD), recommended phase 2 dose, toxicities and efficacy in men with castrate-resistant prostate cancer (CRPC).METHODSThis open label phase 1/2a study utilizes a time-to-event reassessment method (TITE-CRM) design. Patients in cohorts of 3 were treated with escalating doses of APC-100 (900 mg-2400 mg) orally once daily continuously. Cycles were 28 days.RESULTSTwenty patients with CRPC were enrolled in the dose escalation cohort. One possible DLT (elevated ALT) was seen at dose level 1. No other DLTs were seen and no dose reductions were required. Most frequent AEs included nausea (grade 1 in 6 patients) and elevated transaminases (grade 1-3 in 5 patients). After enrolment of 20 patients the MTD was not reached, however the maximal feasible dose was exceeded due to the number of capsules ingested. Five of the 20 patients had stable disease as their best response. The median progression free survival (PFS) for the cohort was 2.8 months (range 1-8).CONCLUSIONSAPC-100 is a novel agent with dual mechanism of action functioning both as potent antioxidant as well as antiandrogen. No detectable APC-100 was found in the plasma at dose level 5 (2100 mg) and it was felt that maximal feasibility was nearly reached. APC-100 is being reformulated as a tablet to allow further dose escalation. Once a recommended phase 2 dose is established, future studies in prostate cancer chemoprevention should be conducted.

2013-12-01·Intensive Care Medicine Experimental

Activated protein C ameliorates impaired renal microvascular oxygenation and sodium reabsorption in endotoxemic rats

Article

作者: Egbert G Mik ; Tanja Johannes ; Emre Almac ; Klaus E Unertl ; AB Johan Groeneveld ; Rick Bezemer ; Can Ince

AbstractIntroductionWe aimed to test whether continuous recombinant human activated protein C (APC) administration would be able to protect renal oxygenation and function during endotoxemia in order to provide more insight into the role of coagulation and inflammation in the development of septic acute kidney injury.MethodsIn anesthetized, mechanically ventilated Wistar rats, endotoxemia was induced by lipopolysaccharide administration (10 mg/kg i.v. over 30 min). One hour later, the rats received fluid resuscitation with 0 (LPS + FR group;n= 8), 10 (APC10 group;n= 8), or 100 (APC100 group;n= 8) μg/kg/h APC for 2 h. Renal microvascular oxygenation in the cortex and medulla were measured using phosphorimetry, and renal creatinine clearance rate and sodium reabsorption were measured as indicators of renal function. Statistical significance of differences between groups was tested using two-way ANOVA with Bonferronipost hoctests.ResultsAPC did not have notable effects on systemic and renal hemodynamic and oxygenation variables or creatinine clearance. The changes in renal microvascular oxygenation in both the cortex (r= 0.66;p< 0.001) and medulla (r= 0.80;p< 0.001) were correlated to renal sodium reabsorption.ConclusionRenal sodium reabsorption is closely correlated to renal microvascular oxygenation during endotoxemia. In this study, fluid resuscitation and APC supplementation were not significantly effective in protecting renal microvascular oxygenation and renal function. The specific mechanisms responsible for these effects of APC warrant further study.

100 项与 APC-100 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB13111

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
晚期前列腺癌	申请上市	美国	DMK Pharmaceuticals Corp.	2011-08-01
前列腺癌	临床2期	-	Adamis	-

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT01436214 (ASCO_GU2015)	临床1/2期	晚期前列腺癌	20	APC-100	(鑰鹹鹽構觸蓋糧鬱壓鹽) = 繭獵顧顧壓築醖淵鹽繭夢襯餘鏇範衊鹽鏇憲簾 (構獵壓糧鏇鑰淵選淵鹽 )	-	2015-03-01