Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Biomarkers for efficacy of aliskiren as a hypertensive agent

An antihypertensive drug, a technique for high blood pressure, applied in the field of genetic polymorphism

Inactive Publication Date: 2008-03-19
NOVARTIS AG
View PDF61 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Such traditional practice often results in treatment options that are not optimal for the efficacy of a given drug therapy or for minimizing the likelihood of side effects for an individual subject

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Biomarkers for efficacy of aliskiren as a hypertensive agent

Examples

Experimental program
Comparison scheme
Effect test

Embodiment I

[0018] All doses of active treatment were statistically superior to placebo at clinical trial endpoints for mean sitting systolic blood pressure (MSSBP). Both 300 and 600 mg aliskiren were statistically stronger than placebo and irbesartan at clinical trial endpoints. Similar reductions in MSSBP were obtained with 150 mg Aliskiren and 150 mg Irbesartan. Aliskiren 300 mg and 600 mg produced the greatest reduction, see Example I below.

[0019] In the pharmacogenetic analysis, 48 ​​polymorphisms from the renin-angiotensin-aldosterone system (RAS) or 12 genes previously implicated in blood pressure regulation were examined. One polymorphism in the angiotensin converting enzyme (ACE) gene (SNP_4769, SEQ ID NO: 1), two polymorphisms in the angiotensin II receptor type 2 (AGTR2) gene (SNP_1445, SEQ ID NO: 2 and SNP_4795, SEQ ID NO: 3) and the clinical parameters of mean sitting diastolic and systolic blood pressure drop. No such effect was found for irbesartan and placebo treatme...

Embodiment

[0181] Aliskiren versus placebo and irbesartan in patients with mild to moderate essential hypertension Introduction and Overview

[0182] A retrospective pharmacogenetic analysis was performed in an attempt to evaluate the potential association between genetic variants and clinical outcomes in clinical trials. Specifically, 48 polymorphisms were detected in 12 genes from the renin-angiotensin-aldosterone system (RAS) or previously shown to be involved in blood pressure regulation. Between one polymorphism in the angiotensin-converting enzyme (ACE) gene, two polymorphisms in the angiotensin II receptor type II (AGTR2) gene, and clinical parameters of mean sitting diastolic and systolic blood pressure drop A significant correlation can be seen. These effects were not seen with irbesartan and placebo treatment, instead the effect was specific to aliskiren treatment in this analysis.

[0183] Clinical Trials

[0184] A multi-channel randomized double-blind parallel group clini...

Embodiment II

[0241] Clinical Pharmacogenetic Analysis of Clinical Trial A2203

[0242] Introduction and Overview

[0243] A retrospective pharmacogenetic analysis was performed in an attempt to assess the potential correlation between genetic variation and clinical outcomes in clinical trials, see Example I. Subsequently, for repeat analysis, the results of another clinical trial (A2203) were considered. Specifically, we examined 48 polymorphisms in 12 genes from the renin-angiotensin-aldosterone system (RAS) and previously implicated in blood pressure regulation.

[0244] In Example 1, one polymorphism in the angiotensin-converting enzyme (ACE) gene, two polymorphisms in the angiotensin II receptor type 2 (AGTR2) gene were associated with the clinical parameters mean sitting diastolic blood pressure and systolic A significant correlation was seen between the pressure drop. These effects were not seen with irbesartan and placebo treatment. Furthermore, for the ACE missense variant (Pro...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

A retrospective pharmacogenetic analysis was conducted in an attempt to evaluate potential association between genetic variation and outcome of a clinical trial of efficacy of aliskiren as an antihypertensive agent. Forty-eight polymorphisms were examined in twelve genes from the renin-angiotensin-aldosterone system (RAS) or previously implicated in blood pressure regulation. Significant associations were seen between one polymorphism in the angiotensin converting enzyme (ACE) gene, two polymorphisms in the angiotensin II type 2 receptor (AGTR2) gene, and clinical parameters of mean sitting diastolic and systolic blood pressure decrease. These effects were not found with irbesartan and placebo treatment, but instead were specific to aliskiren treatment.

Description

field of invention [0001] The present invention relates generally to analytical testing of in vitro tissue samples, and more particularly to genetic polymorphisms indicative of the efficacy of aliskiren as an antihypertensive agent. Background of the invention [0002] The renin-angiotensin system (RAS) plays an important role in the regulation of blood pressure and volume homeostasis. The kidneys secrete renin in response to a decrease in circulating volume and blood pressure, which cleaves the substrate angiotensin to form the inactive decapeptide angiotensin I (AngI). AngI is converted to the active octapeptide AngII by angiotensin converting enzyme (ACE). AngII interacts with cellular receptors, induces vasoconstriction, and releases catecholamines from the adrenal medulla and presynaptic nerve terminals. It also promotes aldosterone secretion and sodium reabsorption. In addition, AngII inhibits renin release, thereby providing negative feedback to the system. Thus, ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68A61K9/20
Inventor J·顾J·迈耶
Owner NOVARTIS AG
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com