TREATMENT
The present invention relates to a compound for use in a method of increasing trough lung function in a patient suffering from chronic obstructive pulmonary disease (COPD), wherein the compound is ensifentrine or a pharmaceutically acceptable salt thereof. The invention also relates to a compound for use in treating chronic obstructive pulmonary disease (COPD) in a patient, wherein: the compound is ensifentrine or a pharmaceutically acceptable salt thereof and the patient is susceptible to disturbed sleep.
1 . A method of increasing trough lung function in a human subject having chronic obstructive pulmonary disease (COPD), the method comprising administering to the human subject via inhalation two or more doses of a composition comprising a therapeutically effective amount of ensifentrine or a pharmaceutically acceptable salt thereof, wherein the trough lung function is increased by at least about 40 mL as determined by FEV 1 of the human subject about 11.5 hours to about 12 hours following a prior administration of the composition compared to FEV 1 of the human subject prior to a first administration of the composition to the human subject.
2 . The method of claim 1 , wherein the composition is administered to the human subject as a maintenance therapy.
3 . The method of claim 1 , wherein the trough lung function is measured about 12 hours following a prior administration of the composition to the human subject.
4 . The method of claim 1 , wherein the trough lung function is measured within one hour prior to an administration of the composition to the human subject.
5 . The method of claim 1 , wherein the COPD is moderate COPD.
6 . The method of claim 1 , when the COPD is severe COPD.
7 . The method of claim 1 , wherein the increasing trough lung function reduces sleep disruption in the human subject.
8 . The method of claim 1 , wherein the trough lung function is increased by at least about 49 mL.
9 . The method of claim 1 , wherein the administering to the human subject is twice per day in a first dose and a second dose.
10 . The method of claim 9 , wherein the first dose and the second dose are administered to the human subject in equal amounts.
11 . The method of claim 9 , wherein the first dose is administered to the human subject in the morning and the second dose is administered to the human subject in the evening.
12 . The method of claim 9 , wherein the first dose is administered within three hours after the human subject waking, and the second dose is administered within three hours before the human subject sleeps.
13 . The method of claim 9 , wherein the first dose and the second dose are administered to the human subject from 10 to 14 hours apart.
14 . The method of claim 1 , wherein the therapeutically effective amount of the ensifentrine or the pharmaceutically acceptable salt thereof is 2 mg to 4 mg.
15 . The method of claim 14 , wherein the therapeutically effective amount of the ensifentrine or the pharmaceutically acceptable salt thereof is 3 mg.
16 . The method of claim 1 , wherein the composition is a suspension.
17 . The method of claim 16 , wherein the suspension comprises particles, wherein the particles comprise at least 90 weight percent ensifentrine relative to total weight of the particles.
18 . The method of claim 16 , wherein the suspension comprises particles, wherein the particles comprise at least 99 weight percent ensifentrine relative to total weight of the particles.
19 . The method of claim 16 , wherein the suspension comprises 3 mg ensifentrine free base.
20 . The method of claim 16 , wherein the suspension comprises particles, wherein the particles have a particle size distribution with a Dv50 of from 0.5μm to 5 gm.
21 . The method of claim 16 , wherein the suspension comprises particles, wherein the particles have a particle size distribution with a Dv50 of from 1 gm to 2 gm.
22 . The method of claim 16 , wherein the suspension comprises:
a. ensifentrine particles at a concentration of from 1 to 1.4 mg/mL;
b. polysorbate 20 (Tween 20) at a concentration of from 0.3 to 0.7 mg/mL;
c. sorbitan monolaurate (Span 20) at a concentration of from 0.0 to 0.1 mg/mL;
d. sodium dihydrogen phosphate dihydrate at a concentration of from 0.5 to 1 mg/mL;
e. disodium hydrogen phosphate dihydrate at a concentration of from 0.5 to 1 mg/mL;
f. sodium chloride at a concentration of from 5 to 10 mg/mL; and
g. water.
23 . The method of claim 16 , wherein the suspension comprises:
a. 1.2 mg/ml ensifentrine;
b. 0.50m g/ml polysorbate 20;
c. 0.05 mg/ml sorbitan monolaurate;
d. 0.744 mg/ml sodium dihydrogen phosphate dihydrate;
e. 0.853 mg/ml disodium hydrogen phosphate dihydrate;
f. 8.60 mg/ml sodium chloride; and
g. water.
24 . The method of claim 1 , wherein the method further comprises administrating to the human subject a muscarinic receptor antagonist, a beta-adrenergic receptor agonist, an inhaled corticosteroid, or a combination thereof.
25 . The method of claim 24 , wherein the muscarinic receptor agonist is a long-acting muscarinic receptor antagonist (LAMA).
26 . The method of claim 25 , wherein the LAMA is aclidinium, darotropium, tiotropium, glycopyrrolate, or umeclidinium.
27 . The method of claim 24 , wherein the beta-adrenergic receptor agonist is a long-acting beta-adrenergic receptor agonist (LABA).
28 . The method of claim 27 , wherein the LABA is salmeterol, formoterol, indacaterol, vilanterol, olodaterol, abediterol or carmoterol.
29 . The method of claim 24 , wherein the inhaled corticosteroid is beclomethosone, budesonide, fluticasone propionate, ciclesonide, mometasone, or fluticasone furoate.
30 . The method of claim 24 , wherein the beta-adrenergic receptor agonist is salbutamol.