Pharmaceutical Composition For The Treatment Of Pulmonary Arterial Hypertension

Abstract

The present invention relates to high doses of macitentan, i.e. propylsulfamic acid [5-(4-bromo-phenyl)-6-[2-(5-bromo-pyrimidin-2-yloxy)-ethoxy]-pyrimidin-4-yl]-amide or pharmaceutically acceptable salts, solvates, hydrates or morphological forms thereof, or of aprocitentan, for use in the treatment and/or prevention of pulmonary arterial hypertension (PAH). Moreover, the present invention relates to the use of high doses of macitentan, or of aprocitentan, for the manufacture of a medicament for the treatment and/or prevention of PAH, as well as to a method for the treatment and/or prevention of PAH comprising high doses of macitentan or of aprocitentan. Further, the present invention relates to a dosage regimen for the treatment and/or prevention of PAH as well as to a combination of macitentan, or of aprocitentan, with one or more phosphodiesterase type 5 (PDE5) inhibitors, prostacyclin analogues, prostacyclin receptor agonists or soluble guanylate cyclase stimulators. Therein, PAH is preferably mild or moderate PAH. Moreover, the present invention relates to a pharmaceutical composition for the treatment of PAH comprising a high dose of macitentan or of aprocitentan.

What is claimed is: 
     
         1 . A method for treating pulmonary arterial hypertension (PAH) with macitentan and a phosphodiesterase type 5 (PDE5) inhibitor, comprising administering to a human patient in need thereof macitentan at a dosage of 60 mg to 90 mg per day and a PDE5 inhibitor. 
     
     
         2 . The method of  claim 1 , wherein the dosage of macitentan is 30 mg to 45 mg twice per day. 
     
     
         3 . The method of  claim 1 , wherein the dosage of macitentan is 70 mg to 80 mg per day. 
     
     
         4 . The method of  claim 3 , wherein the dosage of macitentan is 35 mg to 40 mg twice per day. 
     
     
         5 . The method of  claim 1 , wherein the dosage of macitentan is 75 mg per day. 
     
     
         6 . The method of  claim 5 , wherein the dosage of macitentan is 37.5 mg twice per day. 
     
     
         7 . The method of  claim 1 , wherein the method reduces a morbidity risk, a mortality risk, or both, of the PAH. 
     
     
         8 . The method of  claim 1  , wherein the PAH is mild or moderate PAH. 
     
     
         9 . The method of  claim 8 , wherein the PAH is moderate PAH. 
     
     
         10 . The method of  claim 1 , wherein the patient is already being treated with an endothelin receptor antagonist prior to administering macitentan. 
     
     
         11 . The method of  claim 10 , wherein the endothelin receptor antagonist is bosentan or ambrisentan. 
     
     
         12 . The method of  claim 1  , wherein the PDE5 inhibitor is sildenafil, tadalafil, vardenafil, or udenafil. 
     
     
         13 . The method of  claim 12 , wherein the PDE5 inhibitor is tadalafil. 
     
     
         14 . The method of  claim 13 , wherein the tadalafil is administered at a dosage of 20 mg to 40 mg per day. 
     
     
         15 . The method of  claim 14 , wherein the tadalafil is administered at a dosage of 40 mg per day. 
     
     
         16 . The method of  claim 3 , wherein the PDE5 inhibitor is sildenafil, tadalafil, vardenafil, or udenafil. 
     
     
         17 . The method of  claim 16 , wherein the PDE5 inhibitor is tadalafil. 
     
     
         18 . The method of  claim 17 , wherein the tadalafil is administered at a dosage of 20 mg to 40 mg per day. 
     
     
         19 . The method of  claim 18 , wherein the tadalafil is administered at a dosage of 40 mg per day. 
     
     
         20 . The method of  claim 5 , wherein the PDE5 inhibitor is sildenafil, tadalafil, vardenafil, or udenafil. 
     
     
         21 . The method of  claim 20 , wherein the PDE5 inhibitor is tadalafil. 
     
     
         22 . The method of  claim 21 , wherein the tadalafil is administered at a dosage of 20 mg to 40 mg per day. 
     
     
         23 . The method of  claim 22 , wherein the tadalafil is administered at a dosage of 40 mg per day. 
     
     
         24 . The method of  claim 6 , wherein the PDE5 inhibitor is sildenafil, tadalafil, vardenafil, or udenafil. 
     
     
         25 . The method of  claim 24 , wherein the PDE5 inhibitor is tadalafil. 
     
     
         26 . The method of  claim 25 , wherein the tadalafil is administered at a dosage of 20 mg to 40 mg per day. 
     
     
         27 . The method of  claim 26 , wherein the tadalafil is administered at a dosage of 40 mg per day.