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 - 58 . (canceled) 
     
     
         59 . A method for providing an improved prognosis for a human subject having pulmonary arterial hypertension (PAH), the method comprising administering to the subject ambrisentan in combination with a PDE5 inhibitor selected from sildenafil, tadalafil and vardenafil 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 an initiation of administration of ambrisentan and the PDE5 inhibitor is not greater than about 2 years from first diagnosis of the PAH in the human subject. 
   
     
     
         60 . The method of  claim 59 , wherein the dose, frequency and period of administration are effective to provide a reduction of at least about 25% in probability of a clinical worsening event during the treatment period. 
     
     
         61 . The method of  claim 59 , wherein the dose, frequency and period of administration are effective to provide a reduction of at least about 50% in probability of a clinical worsening event during the treatment period. 
     
     
         62 . The method of  claim 59 , wherein the dose, frequency and period of administration are effective to provide a reduction of at least about 80% in probability of a clinical worsening event during the treatment period. 
     
     
         63 . The method of  claim 59 , wherein the dose, frequency and period of 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. 
     
     
         64 . The method of  claim 59 , wherein the dose, frequency and period of administration are effective to provide a reduction from baseline of at least about 15% in BNP concentration. 
     
     
         65 . The method of  claim 59 , wherein the dose, frequency and period of administration are effective to provide a reduction from baseline of at least about 25% in BNP concentration. 
     
     
         66 . The method of  claim 59 , wherein the dose, frequency and period of administration are effective to provide a reduction from baseline of at least about 50% in BNP concentration. 
     
     
         67 . The method of  claim 59 , wherein the human 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.   
     
     
         68 . The method of  claim 59 , wherein the human subject at baseline has mean PAP at rest of at least about 40 mmHg. 
     
     
         69 . The method of  claim 59 , wherein the ambrisentan is administered orally once a day. 
     
     
         70 . The method of  claim 59 , wherein the ambrisentan is administered in a daily dosage amount of about 1 mg to about 25 mg. 
     
     
         71 . The method of  claim 59 , wherein the ambrisentan is administered in a daily dosage amount of about 2.5 mg to about 10 mg. 
     
     
         72 . The method of  claim 59 , wherein the dose, frequency and period of administration are additionally effective to improve pulmonary function of the human subject over baseline as measured by at least one of exercise capacity and/or BDI. 
     
     
         73 . The method of  claim 59 , wherein the dose, frequency and period of administration are additionally effective to enhance quality of life of the human subject over baseline as measured by an increase in one or more parameters in an SF-36® health survey. 
     
     
         74 . The method of  claim 73 , wherein an increase of at least about 1 point is observed in one or more parameters in the survey. 
     
     
         75 . The method of  claim 59 , wherein the dose, frequency and period of administration are additionally effective to maintain or improve WHO functional class. 
     
     
         76 . A method for prolonging life of a human subject having PAH, comprising administering to the human subject ambrisentan in combination with a PDE5 inhibitor selected from sildenafil, tadalafil and vardenafil 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.   
     
     
         77 . A method for extending time to clinical worsening in a human subject having PAH, comprising administering to the human subject ambrisentan in combination with a PDE5 inhibitor selected from sildenafil, tadalafil and vardenafil 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.   
     
     
         78 . A method for treating PAH in a reproductively active human male subject, the method comprising administering to the human male subject a therapeutically effective amount of ambrisentan in combination with a therapeutically effective amount of PDE5 inhibitor selected from sildenafil, tadalafil and vardenafil, wherein fertility of the male subject is not substantially compromised,
 wherein, at baseline, time from first diagnosis of the condition in the subject is not greater than about 2 years.   
     
     
         79 . A method for treating PAH in a human subject, comprising administering to the human subject a therapeutically effective amount of ambrisentan in combination with a therapeutically effective amount of PDE5 inhibitor selected from sildenafil, tadalafil and vardenafil, 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, and
 wherein, at baseline, time from first diagnosis of the condition in the human subject is not greater than about 2 years.   
     
     
         80 . A method for treating a pulmonary hypertension condition classified in WHO Groups 2-5 in a human subject, comprising administering to the human subject a therapeutically effective amount of ambrisentan in combination with a therapeutically effective amount of PDE5 inhibitor selected from sildenafil, tadalafil and vardenafil,
 wherein, at baseline, time from first diagnosis of the condition in the human subject is not greater than about 2 years.   
     
     
         81 . The method of  claim 80 , wherein the condition comprises left-sided atrial or ventricular heart disease and/or left-sided valvular heart disease. 
     
     
         82 . The method of  claim 80 , 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. 
     
     
         83 . The method of  claim 59 , wherein the ambrisentan and the PDE5 inhibitor are coformulated to provide a fixed-dose combination. 
     
     
         84 . The method of  claim 83 , wherein the fixed-dose combination is administered orally once a day. 
     
     
         85 . The method of  claim 83 , wherein the ambrisentan is administered in a daily dosage amount of about 1 mg to about 25 mg. 
     
     
         86 . The method of  claim 83 , wherein the ambrisentan is administered in a daily dosage amount of about 2.5 mg to about 10 mg.