Method for treating a pulmonary hypertension condition

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.

What is claimed is: 
     
         1 . A method for treating a pulmonary hypertension condition in a subject, comprising administering a therapeutically effective amount of ambrisentan to the subject, wherein, at baseline, time from first diagnosis of the condition in the subject is not greater than about 2 years. 
     
     
         2 . The method of  claim 1 , wherein the pulmonary hypertension condition comprises pulmonary arterial hypertension (PAH). 
     
     
         3 . The method of  claim 2 , wherein the PAH comprises idiopathic PAH, familial PAH or PAH associated with another disease or condition. 
     
     
         4 . The method of  claim 2 , wherein the PAH at baseline is of at least WHO Class II. 
     
     
         5 . The method of  claim 1 , wherein, at baseline, time from first diagnosis of the condition in the subject is not greater than about 0.5 years. 
     
     
         6 . The method of  claim 1 , wherein the subject experiences at least one of
 (a) adjustment of one or more hemodynamic parameters indicative of improvement of the pulmonary hypertension condition towards a more normal level versus baseline;   (b) increase in exercise capacity versus baseline;   (c) lowering of Borg dyspnea index (BDI) versus baseline;   (d) improvement of one or more quality of life parameters versus baseline; and/or   (e) movement to a lower WHO functional class.   
     
     
         7 . The method of  claim 6 , wherein mean pulmonary arterial pressure (PAP) is lowered by at least about 3 mmHg versus baseline. 
     
     
         8 . The method of  claim 6 , wherein mean PAP is lowered by at least about 5 mmHg versus baseline. 
     
     
         9 . The method of  claim 6 , wherein exercise capacity is increased as measured by an increase of at least about 10 m in 6-minute walking distance (6MWD). 
     
     
         10 . The method of  claim 6 , wherein exercise capacity is increased as measured by an increase of at least about 20 m in 6MWD. 
     
     
         11 . The method of  claim 6 , wherein BDI is lowered by at least about 0.5 index point versus baseline. 
     
     
         12 . The method of  claim 6 , wherein BDI is lowered by at least about 1 index point versus baseline. 
     
     
         13 . The method of  claim 1 , wherein the ambrisentan is administered orally once a day. 
     
     
         14 . The method of  claim 13 , wherein the ambrisentan is administered in a daily dosage amount of about 1 mg to about 25 mg. 
     
     
         15 . The method of  claim 13 , wherein the ambrisentan is administered in a daily dosage amount of about 2.5 mg to about 10 mg. 
     
     
         16 . The method of  claim 1 , wherein the ambrisentan is administered for a treatment period of at least about one month. 
     
     
         17 . The method of  claim 16 , wherein the treatment period is at least about three months. 
     
     
         18 . The method of  claim 1 , wherein the ambrisentan is administered in monotherapy. 
     
     
         19 . The method of  claim 1 , wherein the ambrisentan is administered in combination therapy with a second active agent effective for treatment of the pulmonary hypertension condition or a condition related thereto. 
     
     
         20 . The method of  claim 19 , wherein the second active agent comprises at least one drug selected from the group consisting of prostanoids, phosphodiesterase-5 (PDE5) inhibitors, endothelin receptor antagonists (ERAs) other than ambrisentan, calcium channel blockers, diuretics, anticoagulants, oxygen and combinations thereof. 
     
     
         21 . A method for providing an improved prognosis for a subject having a pulmonary hypertension condition, the method comprising administering to the subject ambrisentan at a dose and frequency and for a treatment period effective to provide
 (a) a reduction in probability of a clinical worsening event during the treatment period, and/or   (b) a reduction from baseline in serum brain natriuretic peptide (BNP) concentration,   
       wherein, at baseline, time from first diagnosis of the condition in the subject is not greater than about 2 years. 
     
     
         22 . The method of  claim 21 , wherein, at baseline, time from first diagnosis of the condition in the subject is not greater than about 0.5 years. 
     
     
         23 . The method of  claim 21 , wherein the dose, frequency and period of ambrisentan administration are effective to provide a reduction of at least about 25% in probability of a clinical worsening event during the treatment period. 
     
     
         24 . The method of  claim 21 , wherein the dose, frequency and period of ambrisentan administration are effective to provide a reduction of at least about 50% in probability of a clinical worsening event during the treatment period. 
     
     
         25 . The method of  claim 21 , wherein the dose, frequency and period of ambrisentan administration are effective to provide a reduction of at least about 80% in probability of a clinical worsening event during the treatment period. 
     
     
         26 . The method of  claim 21 , wherein the dose, frequency and period of ambrisentan administration are effective to provide a reduction of at least about 50% in probability of death, lung transplantation, hospitalization for pulmonary arterial hypertension, atrial septostomy or an aggregate thereof during the treatment period. 
     
     
         27 . The method of  claim 21 , wherein the dose, frequency and period of ambrisentan administration are effective to provide a reduction from baseline of at least about 15% in BNP concentration. 
     
     
         28 . The method of  claim 21 , wherein the dose, frequency and period of ambrisentan administration are effective to provide a reduction from baseline of at least about 25% in BNP concentration. 
     
     
         29 . The method of  claim 21 , wherein the dose, frequency and period of ambrisentan administration are effective to provide a reduction from baseline of at least about 50% in BNP concentration. 
     
     
         30 . The method of  claim 21 , wherein the pulmonary hypertension condition comprises PAH. 
     
     
         31 . The method of  claim 30 , wherein the subject has idiopathic PAH. 
     
     
         32 . The method of  claim 30 , wherein the subject has non-idiopathic PAH. 
     
     
         33 . The method of  claim 32 , wherein the non-idiopathic PAH is secondary to scleroderma, systemic lupus erythematosus, anorexigen use or HIV infection. 
     
     
         34 . The method of  claim 30 , wherein the PAH at baseline is of at least WHO Class II. 
     
     
         35 . The method of  claim 21 , wherein the subject at baseline has at least one of
 (a) mean PAP of at least about 25 mmHg at rest or at least about 30 mmHg while exercising,   (b) pulmonary vascular resistance (PVR) of at least about 3 mmHg/L/min, and/or   (c) pulmonary capillary wedge pressure (PCWP) or left ventricle end diastolic pressure (LVEDP) not greater than about 15 mmHg.   
     
     
         36 . The method of  claim 35 , wherein the subject the subject at baseline has all three of
 (a) mean PAP of at least about 25 mmHg at rest or at least about 30 mmHg while exercising,   (b) PVR of at least about 3 mmHg/L/min, and   (c) PCWP or LVEDP not greater than about 15 mmHg.   
     
     
         37 . The method of  claim 21 , wherein the subject at baseline has mean PAP at rest of at least about 40 mmHg. 
     
     
         38 . The method of  claim 21 , wherein the ambrisentan is administered orally once a day. 
     
     
         39 . The method of  claim 38 , wherein the ambrisentan is administered in a daily dosage amount of about 1 mg to about 25 mg. 
     
     
         40 . The method of  claim 38 , wherein the ambrisentan is administered in a daily dosage amount of about 2.5 mg to about 10 mg. 
     
     
         41 . The method of  claim 21 , wherein the treatment period is at least about one month. 
     
     
         42 . The method of  claim 21 , wherein the treatment period is at least about three months. 
     
     
         43 . The method of  claim 21 , wherein the ambrisentan is administered in monotherapy. 
     
     
         44 . The method of  claim 21 , wherein the ambrisentan is administered in combination therapy with a second active agent effective for treatment of the pulmonary hypertension condition or a condition related thereto. 
     
     
         45 . The method of  claim 44 , wherein the second active agent comprises at least one drug selected from the group consisting of prostanoids, phosphodiesterase-5 (PDE5) inhibitors, endothelin receptor antagonists (ERAs) other than ambrisentan, calcium channel blockers, diuretics, anticoagulants, oxygen and combinations thereof. 
     
     
         46 . The method of  claim 21 , wherein the dose, frequency and period of ambrisentan administration are additionally effective to improve pulmonary function of the subject over baseline as measured by at least one of exercise capacity and/or BDI. 
     
     
         47 . The method of  claim 21 , wherein the dose, frequency and period of ambrisentan administration are additionally effective to enhance quality of life of the subject over baseline as measured by an increase in one or more parameters in an SF-36® health survey. 
     
     
         48 . The method of  claim 47 , wherein an increase of at least about 1 point is observed in one or more parameters in the survey. 
     
     
         49 . The method of  claim 21 , wherein the dose, frequency and period of ambrisentan administration are additionally effective to maintain or improve WHO functional class. 
     
     
         50 . The method of  claim 21 , wherein the subject is female. 
     
     
         51 . The method of  claim 21 , wherein the subject is male and fertility of the subject is not substantially compromised. 
     
     
         52 . 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. 
     
     
         53 . A method for extending time to clinical worsening in 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 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. 
     
     
         54 . 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. 
     
     
         55 . A method for treating PAH in a subject, comprising administering a therapeutically effective amount of ambrisentan to the subject, wherein the PAH is associated with one or more of (a) a congenital heart defect, (b) portal hypertension, (c) use of a drug or toxin other than an anorexigen, (d) thyroid disorder, (e) glycogen storage disease, (f) Gaucher disease, (g) hereditary hemorrhagic telangiectasia, (h) hemoglobinopathy, (i) myeloproliferative disorder, (j) splenectomy, (k) pulmonary veno-occlusive disease or (l) pulmonary capillary hemangiomatosis. 
     
     
         56 . A method for treating a pulmonary hypertension condition classified in WHO Groups 2-5 in a subject, comprising administering a therapeutically effective amount of ambrisentan to the subject. 
     
     
         57 . The method of  claim 56 , wherein the condition comprises left-sided atrial or ventricular heart disease and/or left-sided valvular heart disease. 
     
     
         58 . The method of  claim 56 , wherein the condition is associated with one or more of chronic obstructive pulmonary disease (COPD), interstitial lung disease, sleep-disordered breathing, an alveolar hypoventilation disorder, chronic exposure to high altitude, a developmental abnormality, thromboembolic obstruction of proximal and/or distal pulmonary arteries, a non-thrombotic pulmonary embolism, sarcoidosis, histiocytosis X, lymphangiomatosis, and/or compression of pulmonary vessels.