Method for treating a pulmonary hypertension condition

a pulmonary hypertension and pulmonary arterial pressure technology, applied in the direction of biocide, cardiovascular disorder, drug composition, etc., can solve the problems of difficult heart pumping blood through the lungs to be oxygenated, extreme shortness of breath of patients with pulmonary arterial hypertension, and high pulmonary arterial pressure, so as to prolong the life of the subject, improve the prognosis, and reduce the effect of baselin

Inactive Publication Date: 2008-06-12
GILEAD SCI INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0026]There is still further provided a method for prolonging life of a subject having a pulmonary hypertension condition, comprising administering to the subject ambrisentan at a dose and frequency and for a treatment period effective to increase life expectancy, from a time of initiation of treatment, by at least about 30 days; wherein, at baseline, time from first diagnosis of the condition in the subject is not greater than about 2 years.
[0027]There is still further provided a method for extending time to clinical worsening in a subject having PAH, comprising administering to the subject ambrisentan at a dose and frequency and for a treatment period effective to decrease the probability of a clinical worsening event by at least about 25%; wherein, at baseline, time from first diagnosis of the condition in the subject is not greater than about 2 years.
[0028]There is still further provided a method for treating a pulmonary hypertension condition in a reproductively active male subject, the method comprising administering a therapeutically effective amount of ambrisentan to the subject, wherein fertility of the subject is not substantially compromised.

Problems solved by technology

Severe constriction of the blood vessels in the lungs leads to very high pulmonary arterial pressures.
These high pressures make it difficult for the heart to pump blood through the lungs to be oxygenated.
Patients with PAH suffer from extreme shortness of breath as the heart struggles to pump against these high pressures.
Patients with PAH typically develop significant increases in pulmonary vascular resistance (PVR) and sustained elevations in pulmonary artery pressure (PAP), which ultimately lead to right ventricular failure and death.
Patients diagnosed with PAH have a poor prognosis and equally compromised quality of life, with a mean life expectancy of 2 to 5 years from the time of diagnosis if untreated.

Method used

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  • Method for treating a pulmonary hypertension condition
  • Method for treating a pulmonary hypertension condition
  • Method for treating a pulmonary hypertension condition

Examples

Experimental program
Comparison scheme
Effect test

example 1

Methods Example 1

Patients

[0341]The number of subjects enrolled was 192 at 41 investigative sites.

[0342]Men and women, 18 years of age or older, with idiopathic PAH, PAH associated with connective tissue disease (CTD), e.g., mixed CTD, CREST syndrome, systemic sclerosis (scleroderma), overlap syndrome or systemic lupus erythematosus, or PAH associated with anorexigen use or HIV infection were enrolled in this study. Subjects were to have a documented mean PAP ≧25 mmHg, PVR >3 mmHg / L / min, and PCWP or LVEDP <15 mmHg. Subjects must have been able to walk a distance of at least 150 m but no more than 450 m during 2 consecutive 6MWTs to be eligible for inclusion in the study.

Study Design and Treatment

[0343]After a 2 week screening period, eligible subjects were stratified based on the underlying etiology of PAH (idiopathic or non-idiopathic) and were randomized to 1 of 3 treatment groups (placebo, 2.5 mg or 5 mg ambrisentan) in a ratio of 1:1:1. One blinded dose reduction was permitted du...

results example 1

Patients Study Population

[0382]Disposition of randomized subjects is shown in Table 1.1.

TABLE 1.1Subject disposition (% of randomized subjects)2.5 mg5 mgCombinedPlaceboambrisentanambrisentanambrisentan(N = 65)(N = 64)(N = 63)(N = 127)Randomized65(100.0)64(100.0)63(100.0)127(100.0)Completed54(83.1)58(90.6)58(92.1)116(91.3)Withdrew11(16.9)6(9.4)5(7.9)11(8.7)Reasons forwithdrawal:Adverse3(4.6)1(1.6)3(4.8)4(3.1)eventClinical1(1.5)0(0.0)0(0.0)0(0.0)status did notimprove ordeterioratedWithdrawal0(0.0)3(4.7)1(1.6)4(3.1)of consentEarly escape7(10.8)2(3.1)1(1.6)3(2.4)

[0383]A total of 192 subjects, with a mean age of 50.9 years, received at least 1 dose of study drug and were included in the ITT and safety populations. A majority of the subjects enrolled were female (74.5%) and Caucasian (84.9%). Approximately half (51.6%) of the subjects were residents of western Europe or Israel. The remainder of subjects was evenly distributed throughout eastern Europe (24.0%) and South America (24.5%).

[03...

discussion example 1

[0419]The ambrisentan treatment benefit observed by the primary and secondary endpoints of this study was robust, internally consistent, and clinically relevant.

[0420]Both doses demonstrated a statistically significant and clinically relevant improvement in 6MWD that was associated with a significant decrease in BDI. The improvement in 6MWD was nearly twice as large in the 5 mg dose group compared to the 2.5 mg dose group, and improvements in 6MWD were consistently dose-responsive for most subgroups evaluated. Furthermore, plasma BNP, a molecular marker that has been shown to decrease in patients with PAH who demonstrate improvements in 6MWD or hemodynamics, was substantially reduced with ambrisentan treatment. Ultimately, these symptomatic improvements resulted in a patient's self-assessment of an overall better quality of life, as measured by statistically significant improvements in several scales of the SF-36® health survey.

[0421]In addition to the symptomatic improvements obser...

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Abstract

A method for treating a pulmonary hypertension condition such as pulmonary arterial hypertension (PAH) in a subject comprises administering to the subject a therapeutically effective amount of ambrisentan, wherein, at baseline, time from first diagnosis of the condition in the subject is not greater than about 2 years.

Description

[0001]This application claims the benefit of U.S. provisional application Ser. No. 60 / 869,667, filed Dec. 12, 2006, incorporated in its entirety herein by reference.FIELD OF THE INVENTION[0002]The present invention relates to methods useful for treating a subject having a pulmonary hypertension condition, and for improving clinical outcome in such a subject.BACKGROUND OF THE INVENTION[0003]Pulmonary hypertension (PH) has been previously classified as primary (idiopathic) or secondary. Recently, the World Health Organization (WHO) has classified pulmonary hypertension into five groups:[0004]Group 1: pulmonary arterial hypertension (PAH);[0005]Group 2: PH with left heart disease;[0006]Group 3: PH with lung disease and / or hypoxemia;[0007]Group 4: PH due to chronic thrombotic and / or embolic disease; and[0008]Group 5: miscellaneous conditions (e.g., sarcoidosis, histiocytosis X, lymphangiomatosis and compression of pulmonary vessels).See, for example, Rubin (2004) Chest 126:7-10.[0009]Pu...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/505A61P9/12A61P9/00
CPCA61K31/505A61K31/53A61K31/519A61K31/4985A61P9/00A61P9/12A61P11/00
Inventor GERBER, MICHAEL J.DUFTON, CHRISTOPHER
Owner GILEAD SCI INC
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