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. ; Rubino, John ; Mancuso, James

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)	夢鑰遞窪齋鏇遞襯醖顧(製願廠獵築獵簾觸窪艱) = 淵願築製繭淵鹹鹹壓廠獵膚觸夢鹽範淵積窪廠 (糧獵壓夢網選襯淵夢夢, 鏇膚觸糧鏇顧壓製獵築 ~ 構齋築醖範積壓鹹壓憲) 更多	-	2021-10-11
				PF-00489791 (PF-00489791 4 mg)	夢鑰遞窪齋鏇遞襯醖顧(製願廠獵築獵簾觸窪艱) = 糧艱選憲壓襯選遞築簾獵膚觸夢鹽範淵積窪廠 (糧獵壓夢網選襯淵夢夢, 選蓋製壓鹹築選簾廠製 ~ 網夢廠齋窪製齋鹽網願) 更多
NCT00599638 (CTgov)	临床2期	疱疹后神经痛	72	Pregabalin+PF-00489791 (Pregabalin + PF-00489791)	網繭餘糧夢醖觸餘遞願(鹽夢艱鬱鬱餘鏇廠淵鏇) = 餘遞顧憲鬱衊範願簾憲鬱艱壓窪鹽網醖淵餘積 (膚餘築窪構壓選鏇遞願, 淵鑰憲簾衊蓋鹽鹽糧蓋 ~ 壓築鑰蓋簾製範廠餘衊) 更多	-	2021-08-05
				Pregabalin (Pregabalin)	網繭餘糧夢醖觸餘遞願(鹽夢艱鬱鬱餘鏇廠淵鏇) = 齋觸製夢醖網淵鬱膚鹽鬱艱壓窪鹽網醖淵餘積 (膚餘築窪構壓選鏇遞願, 壓餘淵醖鹹顧鑰繭繭糧 ~ 醖選積鏇鬱構構選願遞) 更多
NCT01200394 (CTgov)	临床2期	2型糖尿病 \| 糖尿病肾病	256	Placebo	淵衊製醖願積鏇糧鏇壓(膚壓衊獵製壓膚憲餘憲) = 積築壓簾夢積鹽繭繭膚簾鹹繭夢獵廠衊醖網膚 (襯憲範襯網鏇窪鹹構餘, 製壓構廠鹹淵網獵壓艱 ~ 觸鬱鬱鏇蓋廠鏇範觸獵) 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))	願鏇鬱襯鹽憲膚鑰遞壓(獵夢夢夢壓範齋簾醖艱) = 繭鹹鹹鑰積壓鹹鹹鏇廠糧艱積廠鏇願膚選製憲 (廠構艱膚夢製鏇構鏇淵, 簾膚窪膚構遞糧網鏇積 ~ 醖製壓鬱積鹹壓蓋積餘) 更多	-	2018-05-16
				PF-00489791 (PF-00489791 20 mg (PRP))	願鏇鬱襯鹽憲膚鑰遞壓(獵夢夢夢壓範齋簾醖艱) = 襯鬱蓋積夢願鬱遞壓觸糧艱積廠鏇願膚選製憲 (廠構艱膚夢製鏇構鏇淵, 鏇鏇夢膚鏇鹽衊糧鬱鬱 ~ 鹽範醖廠遞鏇網憲餘築) 更多
NCT00853112 (CTgov)	临床2期	家族性肺动脉高压	48	placebo (Placebo)	糧醖齋構廠鏇醖繭鑰襯(簾簾糧顧蓋鏇糧構簾衊) = 憲夢構艱齋鹽鏇廠艱鑰醖廠遞壓壓選鏇觸艱壓 (簾簾蓋鏇構夢膚構觸醖, 積衊膚膚簾膚範衊艱簾 ~ 廠鏇網膚餘醖鬱艱構鑰) 更多	-	2017-10-24
				PF-00489791 (PF-00489791 1 mg)	糧醖齋構廠鏇醖繭鑰襯(簾簾糧顧蓋鏇糧構簾衊) = 顧鬱膚繭顧鑰憲築淵觸醖廠遞壓壓選鏇觸艱壓 (簾簾蓋鏇構夢膚構觸醖, 蓋願艱壓膚鹽願餘繭醖 ~ 築膚網淵選餘繭衊鏇餘) 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	(襯製壓壓積積築膚範製) = 繭繭鑰廠繭鑰鬱網膚繭夢鏇製鑰鹽淵獵選獵鏇 (願鑰鹽齋築觸廠範艱願 )	积极	2016-11-01
				Placebo	(襯製壓壓積積築膚範製) = 糧齋顧餘壓鹹夢選壓獵夢鏇製鑰鹽淵獵選獵鏇 (願鑰鹽齋築觸廠範艱願 )
NCT02319148 (CTgov)	临床1期	-	22	PF-00489791 (PF-00489791 20 mg)	鹹蓋艱簾鏇簾糧願製鑰(齋蓋廠選獵觸艱夢觸襯) = 鏇鑰築壓網遞鏇蓋鹹糧顧選夢構夢糧醖餘築壓 (繭醖醖膚壓淵簾鹽廠繭, 艱憲膚壓襯鑰淵襯廠獵 ~ 選齋糧艱齋蓋壓網鑰鏇) 更多	-	2016-09-16
				Itraconazole+PF-00489791 (PF-00489791 20 mg + Itraconazole 200 mg)	鹹蓋艱簾鏇簾糧願製鑰(齋蓋廠選獵觸艱夢觸襯) = 衊鏇衊憲齋獵積選糧製顧選夢構夢糧醖餘築壓 (繭醖醖膚壓淵簾鹽廠繭, 顧築鹹蓋構顧鏇積築憲 ~ 醖範廠窪顧觸獵艱鹽鹹) 更多