US 12,433,865 B2
Compositions comprising PGI2-receptor agonists and processes for the preparation thereof
John W. Adams, San Diego, CA (US)
Assigned to ARENA PHARMACEUTICALS, INC., San Diego, CA (US)
Appl. No. 17/055,065
Filed by Arena Pharmaceuticals, Inc., San Diego, CA (US)
PCT Filed May 23, 2019, PCT No. PCT/US2019/033727
§ 371(c)(1), (2) Date Nov. 12, 2020,
PCT Pub. No. WO2019/222764, PCT Pub. Date Nov. 21, 2019.
Claims priority of provisional application 62/672,384, filed on May 16, 2018.
Prior Publication US 2021/0212979 A1, Jul. 15, 2021
Int. Cl. A61K 31/27 (2006.01); A61K 9/20 (2006.01); A61K 9/28 (2006.01); A61K 9/48 (2006.01); A61P 9/12 (2006.01)
CPC A61K 31/27 (2013.01) [A61K 9/2013 (2013.01); A61K 9/2031 (2013.01); A61K 9/2054 (2013.01); A61K 9/28 (2013.01); A61K 9/4858 (2013.01); A61K 9/4866 (2013.01); A61P 9/12 (2018.01)] 9 Claims
 
1. A method for the treatment of pulmonary arterial hypertension (PAH) in a human, comprising:
a dose titration of 2-(((1r,4r)-4-(((4-chlorophenyl(phenyl)carbamoyloxy)methyl)cyclohexyl)methoxy)acetic acid (Compound 1), or a pharmaceutically acceptable salt thereof, that comprises orally administering Compound 1, or a pharmaceutically acceptable salt thereof, at an initial dose that is equivalent to 0.05 mg of Compound 1 once daily for 1 week, measuring the blood plasma level of Compound 1 in the human, increasing the dose in increments each week by a dose that is equivalent to 0.05 mg of Compound 1 once daily until the measured trough blood plasma concentration of Compound 1 in the human is at least 2.5 ng/mL, and maintaining the dose that provides the measured trough blood plasma concentration of Compound 1 in the human of at least 2.5 ng/mL as a therapeutically effective daily maintenance dose;
wherein the human exhibits WHO/New York Heart Association (NYHA) functional class II to IV symptoms; and
wherein the treatment of PAH comprises an improvement of the human in a 6-minute walk distance (6MWD) test as compared to that of a human with PAH not receiving the therapeutically effective amount of Compound 1, or a pharmaceutically acceptable salt, solvate, or hydrate thereof.