Treatment
The invention provides a compound for use in treating or preventing a disease or condition selected from cystic fibrosis, chronic obstructive pulmonary disease (COPD), asthma, mild pulmonary disease, bronchitis, bronchiectasis, idiopathic bronchiectasis, allergic bronchopulmonary aspergillosis, sinusitis, rhinosinusitis, CFTR-related metabolic syndrome (CRMS), pancreatitis, idiopathic chronic pancreatitis and Sjörgren's syndrome, or for use in preventing male infertility caused by congenital absence of the vas deferens, in a patient by modulating CFTR activity, which compound is 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof. The invention also provides a composition comprising (i) 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof and (ii) a leukotriene receptor antagonist. The invention also provides a composition comprising (i) 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof and (ii) a CFTR potentiator or a CFTR corrector.
1. A method for treating or preventing cystic fibrosis in a patient by modulating CFTR activity, which method comprises administering a compound to the patient, which compound is 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof,
wherein the patient has a CFTR mutation selected from the group consisting of class II CFTR mutations and class IV CFTR mutations.
2. A method according to claim 1 , wherein the CFTR mutation is a class IV CFTR mutation.
3. A method according to claim 1 , wherein the CFTR mutation is selected from the group consisting of ΔF508, R117H, R117C, R347P and R334W.
4. A method according to claim 1 , wherein the patient is heterozygous with (i) one allele displaying a class IV CFTR mutation and (ii) the other allele displaying a class II CFTR mutation.
5. A method according to claim 1 , wherein the patient is susceptible to, or suffering from, diarrhoea.
6. A method according to claim 5 , wherein the patient is suffering from a disease selected from the group consisting of ulcerative colitis, Crohn's disease, microscopic colitis, celiac disease, irritable bowel syndrome, bile acid malabsorption, and diverticulitis.
7. A method according to claim 1 , which comprises administering the compound to the patient by inhalation.
8. A method for increasing mucous mobility and/or reducing mucous viscosity, or for use in facilitating mucous membrane clearance from the airways, in a patient suffering from cystic fibrosis, which method comprises administering a compound to the patient, which compound is 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof,
wherein the patient has a CFTR mutation selected from the group consisting of class II CFTR mutations and class IV CFTR mutations.
9. A method of treating or preventing cystic fibrosis in a patient by modulating CFTR activity, which method comprises administering to the patient (a) 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7-tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof and (b) a leukotriene receptor antagonist,
wherein the patient has a CFTR mutation selected from the group consisting of class II CFTR mutations and class IV CFTR mutations.
10. A method of treating or preventing cystic fibrosis in a patient by modulating CFTR activity, which method comprises administering to the patient (a) 9,10-dimethoxy-2-(2,4,6-trimethylphenylimino)-3-(N-carbamoyl-2-aminoethyl)-3,4,6,7tetrahydro-2H-pyrimido[6,1-a]isoquinolin-4-one or a pharmaceutically acceptable acid addition salt thereof and (b) a CFTR potentiator or a CFTR corrector,
wherein the patient has a CFTR mutation selected from the group consisting of class II CFTR mutations and class IV CFTR mutations.