Long-acting injectable formulations comprising an isoxazoline active agent, methods and uses thereof

1. A long-acting injectable formulation for the treatment of parasite infestations or infections in an animal comprising:

a) about 5% to 30% (w/v) of an isoxazoline compound of Formula (Ib):

 or a pharmaceutically acceptable salt thereof

wherein:

R 2 independently is halogen, C 1 -C 6 alkyl or C 1 -C 6 haloalkyl;

R 4 is H or C 1 -C 6 alkyl;

R 5 is C 1 -C 4 alkyl optionally substituted with one or more R 7 ; and R 7 is C 2 -C 7 alkylcarbonyl, C 2 -C 7 alkoxycarbonyl, C 2 -C 7 alkylaminocarbonyl, C 3 -C 9 dialkylaminocarbonyl, C 2 -C 7 haloalkylcarbonyl, C 2 -C 7 haloalkoxycarbonyl, C 2 -C 7 haloalkylaminocarbonyl, C 3 -C 9 dihaloalkylaminocarbonyl; and n is 0, 1 or 2;

b) poloxamer 124 or poloxamer 181;

c) about 5% to 40% (w/v) of a co-solvent selected from the group consisting of liquid polyethylene glycol, ethanol, isopropanol, and a mixture thereof;

d) optionally, about 0.01% to about 2.0% (w/v) of an antioxidant; and

e) optionally about 0.01% to about 5.0% (w/v) of a pharmaceutically acceptable additive, excipient or mixtures thereof;

wherein the only pharmaceutically acceptable polymer present in said long-acting injectable composition is said poloxamer and wherein the poloxamer is present in the overall composition in a proportion representing the complement to 100% of the composition; and

wherein the formulation treats parasitic infestations or infections for about 3 to 6 months.

2. The long-acting injectable formulation according to claim 1 , wherein the isoxazoline active agent is a compound of formula (Ia):

or a pharmaceutically acceptable salt thereof.

3. The long-acting injectable formulation according to claim 1 , wherein the isoxazoline active agent is enriched in an enantiomer.

4. The long-acting injectable formulation according to claim 3 , wherein the isoxazoline active agent is enriched in a compound of formula (S)-(Ia):

or a pharmaceutically acceptable salt thereof.

5. The long-acting injectable formulation according to claim 1 wherein a single injection of the formulation provides at least 80% efficacy against parasite infestations or infections for about 3 to 6 months.

6. The long-acting injectable formulation according to claim 5 wherein a single injection of the formulation provides at least 80% efficacy against parasite infestations or infections for about 5 to 6 months.

7. The long-acting injectable formulation according to claim 5 wherein a single injection of the formulation provides at least 80% efficacy against parasite infestations or infections for about 6 months.

8. The long-acting injectable formulation according to claim 1 , wherein a single injection of the formulation provides at least 80% efficacy against parasite infestations or infections for about 7 months or longer.

9. The long-acting injectable formulation according to any one of claims 5 - 8 wherein the parasites are fleas or ticks.

10. The long-acting injectable formulation according to claim 1 consisting essentially of:

a) about 5 to 30% (w/v) of an isoxazoline active compound of formula (Ia)

or a pharmaceutically acceptable salt thereof,

b) poloxamer 124 or poloxamer 181;

c) about 5% to 40% (w/v) of a co-solvent selected from the group consisting of liquid polyethylene glycol, ethanol, isopropanol, and mixtures thereof;

d) optionally, about 0.01% to about 2.0% (w/v) of an antioxidant; and

e) optionally, about 0.01% to about 5.0% (w/v) of a pharmaceutically acceptable additive, excipient or mixtures thereof;

wherein the only pharmaceutically acceptable polymer present in said long-acting injectable composition is a poloxamer and wherein the poloxamer is present in the overall composition in a proportion representing the complement to 100% of the composition.

11. The long-acting injectable formulation according to claim 10 , wherein the isoxazoline compound is:

or a pharmaceutically acceptable salt thereof.

12. The long-acting formulation according to claim 1 or 11 , which further comprises an effective amount at least one additional pharmaceutically active agent.

13. The long-acting formulation according to claim 12 , wherein the additional pharmaceutically active agent is a macrocyclic lactone.

14. The long-acting formulation according to claim 13 , wherein the macrocyclic lactone is abamectin, dimadectin, doramectin, emamectin, eprinomectin, ivermectin, latidectin, lepimectin, selamectin, milbemectin, milbemycin D, moxidectin or nemadectin.

15. A long-acting injectable formulation for the treatment of parasite infestations or infections in an animal comprising:

a) about 5 to 30% (w/v) of an isoxazoline active compound of formula (Ia):

or a pharmaceutically acceptable salt thereof;

b) at least one pharmaceutically acceptable polymer which is a liquid poloxamer at room temperature (20-25° C.), wherein the liquid poloxamer is poloxamer 124 or poloxamer 181;

c) about 5% to 40% (w/v) of a co-solvent selected from the group consisting of liquid polyethylene glycol, ethanol, isopropanol, and mixtures thereof;

d) optionally, about 0.01% to about 2.0% (w/v) of an antioxidant; and

e) optionally, at least one pharmaceutically acceptable additive, excipient or mixtures thereof;

wherein no other pharmaceutically acceptable polymers are present;

and wherein a single injection of the formulation provides at least 80% efficacy against parasitic infestations or infections for at least 3 months.

16. The long-acting injectable formulation according to claim 15 , wherein the isoxazoline compound is:

or a pharmaceutically acceptable salt thereof.

17. A method for treating a parasitic infection or infestation in an animal in need thereof for a period of 3 to 6 months which comprises administering the long acting injectable formulation according to claim 1 to said animal.

18. The method according to claim 17 wherein the animal is a dog, cat, sheep or cattle.

19. The method according to claim 17 wherein the parasites are treated for about 5 to 6 months.

20. The method according to claim 17 wherein the parasites are treated for about 6 months.

21. The method according to claim 17 wherein the parasites are fleas and/or ticks.