Treatment of RSV with combination product
The present invention is directed to the combination of the RSV inhibiting Compound A, i.e. 3-({5-chloro-1-[3-(methylsulfonyl)propyl]-1H-indol-2-yl}methyl)-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one, and the RSV inhibiting Compound B, i.e. (1S,2S)-2-[4-[7-cyclopropyl-5-[(1R)-1-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]pyrazolo[1,5-a]pyrimidin-2-yl]-3-fluoro-phenyl]cyclopropanecarboxylic acid for treating or ameliorating RSV infection. The invention further relates to the combination product of Compound A and Compound B, a pharmaceutical product comprising Compound A and Compound B, the use of the combination of Compound A and Compound B—or the pharmaceutical product comprising Compound A and Compound B—for the treatment of RSV infection, and a method of treating or ameliorating RSV infection in a subject in need thereof comprising administering the combination of Compound A and Compound B in an effective amount to said subject.
1. A combination comprising:
3-({5-chloro-1-[3-(methylsulfonyl)propyl]-1H-indol-2-yl}methyl)-1-(2,2,2-trifluoroethyl)-1,3-dihydro-2H-imidazo[4,5-c]pyridin-2-one, or a pharmaceutically acceptable salt thereof, as Compound A, and
(1S,2S)-2-[4-[7-cyclopropyl-5-[(1R)-1-methyl-3,4-dihydro-1H-isoquinoline-2-carbonyl]-pyrazolo[1,5-a]pyrimidin-2-yl]-3-fluoro-phenyl]cyclopropanecarboxylic acid, or a pharmaceutically acceptable salt thereof, as Compound B,
wherein the amounts of Compound A and Compound B are such that they produce a synergistic antiviral effect against RSV.
2. The combination of claim 1 , wherein the amount of Compound A ranges from about 50 mg to about 500 mg in free form equivalent and the amount of Compound B ranges from about 50 mg to about 500 mg in free form equivalent.
3. A pharmaceutical composition comprising the combination of claim 1 and a pharmaceutically acceptable carrier.
4. The pharmaceutical composition of claim 3 , wherein the amount of Compound A ranges from about 50 mg to about 500 mg in free form equivalent and the amount of Compound B ranges from about 50 mg to about 500 mg in free form equivalent.
5. The pharmaceutical composition of claim 3 , wherein the composition is an oral pharmaceutical composition.
6. The pharmaceutical composition of claim 5 , wherein the oral pharmaceutical composition is a tablet, a capsule, a solution, or a suspension.
7. The pharmaceutical composition of claim 3 , wherein Compound A and Compound B are formulated in a single pharmaceutical composition.
8. A method for treating or ameliorating respiratory syncytial virus (RSV) infection in a subject in need thereof comprising administering to the subject the combination of claim 1 .
9. The method of claim 8 , wherein Compound A and Compound B are formulated in a single pharmaceutical composition.
10. The method of claim 8 , wherein Compound A is formulated as a first separate pharmaceutical composition and Compound B is formulated as a second separate pharmaceutical composition, and the administering comprises administering the first and second separate pharmaceutical compositions to the subject simultaneously or sequentially.
11. The method of claim 8 , wherein the amount of Compound A ranges from about 50 mg to about 500 mg in free form equivalent and the amount of Compound B ranges from about 50 mg to about 500 mg in free form equivalent.
12. The method of claim 9 , wherein the single pharmaceutical composition is an oral pharmaceutical composition.
13. The method of claim 12 , wherein the oral pharmaceutical composition is a tablet, a capsule, a solution, or a suspension.
14. The method of claim 10 , wherein the first and second separate pharmaceutical compositions are each independently a tablet, a capsule, a solution, or a suspension.
15. The method of claim 8 , comprising administering each of Compound A and Compound B daily to the subject in one, two, three, or four sub-doses at appropriate intervals.
16. The method of claim 8 , wherein Compound A is administered in an amount greater than or equal to a concentration of 0.57 nM or an equivalent thereof.
17. The method of claim 7 , wherein Compound B is administered in an amount greater than or equal to a concentration of 14 nM or an equivalent thereof.