PF-489791(PF-489791) - 药物靶点：PDE5A_专利_临床

概要

基本信息

药物类型

小分子化药

别名

靶点

PDE5A

作用机制

PDE5A抑制剂(磷酸二酯酶-5A抑制剂)

治疗领域

神经系统疾病心血管疾病内分泌与代谢疾病+ [3]

在研适应症-

非在研适应症

2型糖尿病糖尿病肾病原发性高血压+ [4]

原研机构

Pfizer Inc.

在研机构-

非在研机构

Pfizer Inc.

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

分子式C20H28N8O4S

InChIKeyZUHZNKJIJDAJFD-UHFFFAOYSA-N

CAS号853003-48-2

关联

6

项与 PF-489791 相关的临床试验

NCT02319148

/ Completed临床1期

A Phase 1, Randomized, Open-label, 3-sequence, 4-treatment, Incomplete Block Design To Estimate The Effect Of Steady State Cyp3a4 Inhibitors (Itraconazole, Diltiazem Or Verapamil) On The Pharmacokinetics Of Singe Dose Pf-00489791 In Healthy Volunteers

The primary objective of the study is to estimate the effects of different strong enzyme (CYP3A4) inhibitors, itraconazole, diltiazem, or verapamil on the single dose pharmacokinetics of PF-00489791 in healthy volunteers. The study will enroll approximately 18 subjects that are randomized to 1 of 3 treatment groups. The study is also intended to determine the safety and tolerability of single-dose PF- 00489791 when it is administered with steady-state itraconazole, diltiazem, or verapamil.

开始日期2014-07-01

申办/合作机构

Pfizer Inc.

NCT01200394

/ Completed临床2期

A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP, MULTI-CENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ONCE-DAILY ADMINISTRATION OF A PHOSPHODIESTERASE 5 INHIBITOR (PF-00489791) IN ADULTS WITH TYPE 2 DIABETES AND OVERT NEPHROPATHY

PF-00489791 is an inhibitor of phosphodiesterase type 5. Our hypothesis is that PF-00489791 will enhance the relaxation of blood vessels within the kidney and so reduce blood pressure, improving renal function.

开始日期2010-12-01

申办/合作机构

Pfizer Inc.

NCT01090492

/ Completed临床2期

A Phase 2a Randomized Double-blinded, Placebo And Active Controlled Two Cohort Two Doses Cross-over Multi-center Clinical Study To Assess Efficacy Of A Once Daily Administration Of A Phosphodiesterase 5 Inhibitor (Pf-00489791) For The Treatment Of Vasospasm In Primary And Secondary Raynaud's Phenomenon

The investigators propose that once daily administration of PF-00489791, a phosphodiesterase inhibitor, will reduce vasospasm and improve symptoms and signs associated with Primary and Secondary Raynaud's Phenomenon.

开始日期2010-08-04

申办/合作机构

Pfizer Inc.

100 项与 PF-489791 相关的临床结果

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100 项与 PF-489791 相关的转化医学

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100 项与 PF-489791 相关的专利（医药）

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5

项与 PF-489791 相关的文献（医药）

2016-11-01·Journal of the American Society of Nephrology1区 · 医学

Phosphodiesterase Type 5 Inhibition Reduces Albuminuria in Subjects with Overt Diabetic Nephropathy

1区 · 医学

Article

作者: Scheele, Wim ; Diamond, Susan ; Tamimi, Nihad ; Perros-Huguet, Christelle ; Clerin, Valerie ; Gale, Jeremy ; El Nahas, Meguid ; Walley, Rosalind ; Le, Vu ; Rolph, Timothy ; Grover-Páez, Fernando

Diabetic nephropathy (DN) is the leading cause of ESRD worldwide. Reduced bioavailability or uncoupling of nitric oxide in the kidney, leading to decreased intracellular levels of the nitric oxide pathway effector molecule cyclic guanosine monophosphate (cGMP), has been implicated in the progression of DN. Preclinical studies suggest that elevating the cGMP intracellular pool through inhibition of the cGMP-hydrolyzing enzyme phosphodiesterase type 5 (PDE5) might exert renoprotective effects in DN. To test this hypothesis, the novel, highly specific, and long-acting PDE5 inhibitor, PF-00489791, was assessed in a multinational, multicenter, randomized, double-blind, placebo-controlled, parallel group trial of subjects with type 2 diabetes mellitus and overt nephropathy receiving angiotensin converting enzyme inhibitor or angiotensin receptor blocker background therapy. In total, 256 subjects with an eGFR between 25 and 60 ml/min per 1.73 m2 and macroalbuminuria defined by a urinary albumin-to-creatinine ratio >300 mg/g, were randomly assigned 3:1, respectively, to receive PF-00489791 (20 mg) or placebo orally, once daily for 12 weeks. Using the predefined primary assessment of efficacy (Bayesian analysis with informative prior), we observed a significant reduction in urinary albumin-to-creatinine ratio of 15.7% (ratio 0.843; 95% credible interval 0.73 to 0.98) in response to the 12-week treatment with PF-00489791 compared with placebo. PF-00489791 was safe and generally well tolerated in this patient population. Most common adverse events were mild in severity and included headache and upper gastrointestinal events. In conclusion, the safety and efficacy profile of PDE5 inhibitor PF-00489791 supports further investigation as a novel therapy to improve renal outcomes in DN.

2015-09-01·International Urology and Nephrology4区 · 医学

Phosphodiesterase type 5 inhibitors and kidney disease

4区 · 医学

Review

作者: Tarik Esen ; David Goldsmith ; Baris Afsar ; Alberto Ortiz ; Adrian Covic ; Abduzhappar Gaipov ; Mehmet Kanbay

Chronic kidney disease (CKD) represents a worldwide health problem. Traditionally, the nephroprotective treatment for CKD aims to slow progression to end-stage renal disease and includes dietary protein restriction, correction of metabolic acidosis, and renin-angiotensin system blockers. However, current standard therapeutic options may not be enough for preventing CKD progression in a subset of patients making necessary to develop novel therapeutic options to further slow renal function loss. Phosphodiesterase type 5 (PDE5) inhibitors represent a class of drugs traditionally used to treat erectile dysfunction and pulmonary hypertension. However, recent evidence suggests that PDE5 inhibitors may have additional therapeutic effects, such as cardioprotection and cerebrovascular protection. In the current review, we summarize PDE5 inhibitors' utility in disease states and clinical conditions related to kidney disease such as systemic hypertension and acute and chronic kidney injury and discuss the mechanisms explaining possible kidney protective roles of PDE5 inhibitors. A recently completed phase 2 trials demonstrated that the long-acting PDE5 inhibitor PF-00489791 decreased albuminuria in patients with overt diabetic nephropathy when added on top of renin-angiotensin system blockade.

2009-06-01·Hypertension1区 · 医学

Blood Pressure Lowering Effects of a New Long-Acting Inhibitor of Phosphodiesterase 5 in Patients With Mild to Moderate Hypertension

1区 · 医学

Article

作者: Wolk, Robert ; Smith, William B. ; Gilbert, James ; Xuan, Dawei ; Neutel, Joel M. ; Pressler, Milton L. ; Mancuso, James ; Rubino, John

Inhibition of phosphodiesterase 5 is an attractive candidate mechanism for blood pressure (BP) lowering. In this study, a novel long-acting phosphodiesterase 5 inhibitor, PF-00489791, was evaluated in 133 patients with mild to moderate hypertension, randomized into 1 of 4 groups: placebo, 4 mg, 10 mg, and 20 mg titrated after 14 days of dosing to 40 mg. Study medication was administered once daily for 28 days. Ambulatory BP monitoring was used. There was a statistically significant decrease (compared with placebo) in mean daytime systolic BP on day 28 at the 10 and 20/40 mg doses (by ≈5 and ≈7 mm Hg, respectively). Changes in mean daytime diastolic BP corresponded with those in systolic BP. The magnitude of BP lowering was greater on day 1 than on days 14 and 28, but the response was sustained between days 14 and 28. PF-00489791 also exerted BP lowering effects on mean 24-hour ambulatory BP. There was a dose-related increase in plasma cGMP concentration (statistically significant at the 20/40 mg dose). There was an increased incidence of headaches at the 10 and 20/40 mg doses (22% and 21%, respectively, compared with 12% with placebo) and an increased incidence of dyspepsia/gastroesophageal reflux disease and musculoskeletal adverse events at the 20/40 mg dose. In conclusion, PF-00489791 causes a clinically meaningful and sustained BP lowering in patients with hypertension. It is generally safe and well tolerated at the clinically efficacious doses.

100 项与 PF-489791 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB11736

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
家族性肺动脉高压	临床2期	美国	Pfizer Inc.	2009-04-01
家族性肺动脉高压	临床2期	西班牙	Pfizer Inc.	2009-04-01
家族性肺动脉高压	临床2期	瑞士	Pfizer Inc.	2009-04-01
家族性肺动脉高压	临床2期	加拿大	Pfizer Inc.	2009-04-01
家族性肺动脉高压	临床2期	俄罗斯	Pfizer Inc.	2009-04-01
家族性肺动脉高压	临床2期	德国	Pfizer Inc.	2009-04-01
家族性肺动脉高压	临床2期	印度	Pfizer Inc.	2009-04-01
家族性肺动脉高压	临床2期	瑞典	Pfizer Inc.	2009-04-01
疱疹后神经痛	临床2期	美国	Pfizer Inc.	2008-04-09
原发性高血压	临床2期	美国	Pfizer Inc.	2007-02-27

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临床结果

适应症

分期

评价

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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


NCT00422461 (CTgov)	临床2期	原发性高血压	135	placebo (Placebo)	廠範範願壓餘鹽糧鬱觸(遞築襯範蓋簾積願範選) = 窪壓簾餘鏇襯製齋憲顧艱衊範觸衊鑰蓋觸製窪 (鹹鹽衊膚襯鬱觸齋蓋廠, 顧願衊遞糧夢網範繭衊 ~ 製構鑰簾遞鏇選憲膚鬱) 更多	-	2021-10-11
				PF-00489791 (PF-00489791 4 mg)	廠範範願壓餘鹽糧鬱觸(遞築襯範蓋簾積願範選) = 鬱積網範構鏇膚衊醖範艱衊範觸衊鑰蓋觸製窪 (鹹鹽衊膚襯鬱觸齋蓋廠, 鏇選獵繭積網獵願積醖 ~ 窪鹹憲齋鬱選齋顧淵觸) 更多
NCT00599638 (CTgov)	临床2期	疱疹后神经痛	72	Pregabalin+PF-00489791 (Pregabalin + PF-00489791)	鏇蓋製夢鏇繭夢願齋膚(積窪齋築醖遞窪夢窪築) = 鏇選蓋憲齋觸淵鹽鹹壓廠鏇選簾壓選齋齋選製 (製繭簾築衊齋網醖窪網, 廠遞醖餘膚鏇網艱選窪 ~ 遞蓋簾憲鏇鏇範糧觸遞) 更多	-	2021-08-05
				Pregabalin (Pregabalin)	鏇蓋製夢鏇繭夢願齋膚(積窪齋築醖遞窪夢窪築) = 淵憲廠夢蓋窪襯廠鏇艱廠鏇選簾壓選齋齋選製 (製繭簾築衊齋網醖窪網, 餘齋廠繭範製顧夢鹹顧 ~ 醖範觸遞齋願獵鏇繭醖) 更多
NCT01200394 (CTgov)	临床2期	2型糖尿病 \| 糖尿病肾病	256	Placebo	夢糧築選範壓鑰築顧簾(窪構齋糧餘簾醖壓觸鬱) = 淵醖廠鬱鑰獵餘鬱繭醖構製艱鹹鹽壓築簾簾鏇 (製糧衊選獵齋鹽窪鹽顧, 夢憲醖憲衊憲夢製積襯 ~ 築鏇糧製窪積餘鑰憲選) 更多	-	2019-03-12
NCT01090492 (CTgov)	临床2期	雷诺病 \| 血管痉挛	243	PF-00489791 (PF-00489791 4 mg (PRP))	網積範衊範蓋襯鏇淵簾(積範襯齋構製襯鹽衊艱) = 糧願鹹鬱願蓋蓋衊願廠蓋夢壓壓鏇築遞選觸醖 (鑰衊衊襯築遞糧膚鑰簾, 範醖襯膚衊繭鑰繭窪廠 ~ 淵膚糧醖憲襯壓獵鹽選) 更多	-	2018-05-16
				PF-00489791 (PF-00489791 20 mg (PRP))	網積範衊範蓋襯鏇淵簾(積範襯齋構製襯鹽衊艱) = 遞鏇選窪網餘網製窪鬱蓋夢壓壓鏇築遞選觸醖 (鑰衊衊襯築遞糧膚鑰簾, 網積積壓獵製網蓋窪顧 ~ 鹽糧鑰鏇憲衊糧鏇鑰齋) 更多
NCT00853112 (CTgov)	临床2期	家族性肺动脉高压	48	placebo (Placebo)	範鏇簾淵鹽製窪衊廠壓(顧選獵構鹽遞夢艱獵衊) = 夢積繭衊鬱鹹襯膚網窪積襯觸鹽獵鹹遞鬱窪範 (構範願積選選鑰膚憲選, 觸範憲製鹹襯鏇遞鹹願 ~ 鏇構壓鹹襯構襯製壓鑰) 更多	-	2017-10-24
				PF-00489791 (PF-00489791 1 mg)	範鏇簾淵鹽製窪衊廠壓(顧選獵構鹽遞夢艱獵衊) = 廠鹽夢齋網夢構糧鏇鏇積襯觸鹽獵鹹遞鬱窪範 (構範願積選選鑰膚憲選, 壓鹽醖顧積鏇憲積膚餘 ~ 醖窪製顧構壓鏇網簾醖) 更多
NCT01200394 (Pubmed \| J Am Soc Nephrol) 人工标引	临床2期	蛋白尿 \| 糖尿病肾病	256	PF-00489791	(糧鹹網夢憲遞範範廠願) = 築積淵選築醖願製醖獵鏇糧鹹製衊膚夢簾願鬱 (糧鹹顧網觸構積夢簾膚 )	积极	2016-11-01
				Placebo	(糧鹹網夢憲遞範範廠願) = 製選夢鏇觸製構廠膚選鏇糧鹹製衊膚夢簾願鬱 (糧鹹顧網觸構積夢簾膚 )
NCT02319148 (CTgov)	临床1期	-	22	PF-00489791 (PF-00489791 20 mg)	積築憲網夢鬱範鑰糧築(鬱壓鑰獵遞範襯鬱壓繭) = 襯獵餘製願鏇鏇膚構憲範淵繭襯憲膚蓋衊憲醖 (艱鏇觸襯廠淵鏇鬱願簾, 構蓋衊網獵築範窪襯遞 ~ 鑰憲鹹構醖鑰範淵鬱獵) 更多	-	2016-09-16
				Itraconazole+PF-00489791 (PF-00489791 20 mg + Itraconazole 200 mg)	積築憲網夢鬱範鑰糧築(鬱壓鑰獵遞範襯鬱壓繭) = 醖窪範繭繭製願繭觸獵範淵繭襯憲膚蓋衊憲醖 (艱鏇觸襯廠淵鏇鬱願簾, 鑰餘夢壓觸齋觸範遞鬱 ~ 艱繭衊積獵選餘襯壓範) 更多