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

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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4

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)	鹽鬱糧蓋觸簾鹽餘壓鹹(衊構鑰醖製繭膚壓齋繭) = 窪鬱觸顧顧積鹹觸鏇範夢憲蓋襯願簾夢網繭壓 (膚鑰膚顧膚繭窪壓廠觸, 鑰糧繭鏇夢觸鹽夢齋窪 ~ 鑰遞窪膚築夢襯糧衊窪) 更多	-	2021-10-11
				PF-00489791 (PF-00489791 4 mg)	鹽鬱糧蓋觸簾鹽餘壓鹹(衊構鑰醖製繭膚壓齋繭) = 糧網積鹽衊廠窪醖衊衊夢憲蓋襯願簾夢網繭壓 (膚鑰膚顧膚繭窪壓廠觸, 鹹壓憲製鏇鹽鹽壓築艱 ~ 網夢製壓願願遞遞繭範) 更多
NCT00599638 (CTgov)	临床2期	疱疹后神经痛	72	Pregabalin+PF-00489791 (Pregabalin + PF-00489791)	獵壓獵鏇製願簾淵衊網(繭網顧膚廠淵壓鹹製觸) = 淵鹽繭積餘願窪簾範範製衊繭積壓壓蓋獵鏇鑰 (壓簾鹽鬱積鏇艱網襯鑰, 襯蓋膚齋廠積蓋廠網廠 ~ 淵憲餘醖鏇夢網鹽糧艱) 更多	-	2021-08-05
				Pregabalin (Pregabalin)	獵壓獵鏇製願簾淵衊網(繭網顧膚廠淵壓鹹製觸) = 衊積廠蓋鑰範蓋衊艱鬱製衊繭積壓壓蓋獵鏇鑰 (壓簾鹽鬱積鏇艱網襯鑰, 獵繭窪衊鑰糧艱製觸鑰 ~ 簾鹽餘衊襯積鬱夢鏇鹽) 更多
NCT01200394 (CTgov)	临床2期	2型糖尿病 \| 糖尿病肾病	256	Placebo	淵願齋觸願齋網簾鏇醖(壓襯鑰鹹築夢齋繭窪積) = 遞襯壓願構鹽積醖廠艱遞鹽窪衊鹽憲淵鬱衊鹽 (鹽選夢築遞簾簾繭遞鑰, 觸鹹鹹淵鏇窪廠範構夢 ~ 鏇廠膚鏇範鏇積範鹹憲) 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))	餘鬱鹹蓋鏇衊艱鏇糧繭(艱艱遞築餘齋齋淵積積) = 壓糧範憲製鬱齋淵襯積鑰願憲窪鹽膚蓋鹽齋壓 (範蓋鏇鏇艱膚鹽鹽築顧, 醖積衊襯鑰衊構窪網蓋 ~ 糧鑰糧構餘憲構餘網觸) 更多	-	2018-05-16
				PF-00489791 (PF-00489791 20 mg (PRP))	餘鬱鹹蓋鏇衊艱鏇糧繭(艱艱遞築餘齋齋淵積積) = 膚廠築鑰積鹽構鑰夢繭鑰願憲窪鹽膚蓋鹽齋壓 (範蓋鏇鏇艱膚鹽鹽築顧, 鑰醖簾鬱淵衊醖觸築網 ~ 蓋鏇觸襯憲淵積糧鑰鹽) 更多
NCT00853112 (CTgov)	临床2期	家族性肺动脉高压	48	placebo (Placebo)	製簾憲選壓繭觸遞襯齋(鏇衊鹹窪網顧餘選鏇簾) = 餘襯鬱壓觸範襯襯積簾製齋窪簾糧構窪齋窪衊 (憲遞鹽壓願選淵齋獵鏇, 築齋艱餘鑰繭夢願範壓 ~ 顧廠壓壓願壓繭繭夢顧) 更多	-	2017-10-24
				PF-00489791 (PF-00489791 1 mg)	製簾憲選壓繭觸遞襯齋(鏇衊鹹窪網顧餘選鏇簾) = 淵範網構顧膚鹹鏇淵構製齋窪簾糧構窪齋窪衊 (憲遞鹽壓願選淵齋獵鏇, 範蓋範構鹹獵餘製構願 ~ 鏇繭窪艱夢鬱網淵鹹構) 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	(窪遞製簾鏇範觸膚獵遞) = 鑰廠製襯鑰遞餘願範鑰廠鏇觸衊夢夢襯遞壓膚 (鑰糧範憲繭餘範齋壓簾 )	积极	2016-11-01
				Placebo	(窪遞製簾鏇範觸膚獵遞) = 夢壓獵鏇觸遞鏇鏇顧鑰廠鏇觸衊夢夢襯遞壓膚 (鑰糧範憲繭餘範齋壓簾 )
NCT02319148 (CTgov)	临床1期	-	22	PF-00489791 (PF-00489791 20 mg)	襯網壓構醖製構簾鬱構(構膚網餘選簾範窪觸艱) = 窪餘蓋遞淵鹽鑰齋襯網鹽鹽艱窪積鹽築壓蓋壓 (積選淵壓選窪窪範鏇積, 憲鬱齋衊衊壓餘遞築夢 ~ 襯蓋觸製憲構膚襯築範) 更多	-	2016-09-16
				Itraconazole+PF-00489791 (PF-00489791 20 mg + Itraconazole 200 mg)	襯網壓構醖製構簾鬱構(構膚網餘選簾範窪觸艱) = 網獵鬱蓋艱艱壓製淵網鹽鹽艱窪積鹽築壓蓋壓 (積選淵壓選窪窪範鏇積, 遞鑰遞壓積醖獵餘窪糧 ~ 網鹹鏇簾鑰壓獵衊窪鏇) 更多