Method of treating actinic keratosis
View Patent ↗A method of treating actinic keratosis including applying topically to an actinic keratosis lesion twice per week for a duration of 8 weeks a formulation comprising 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine.
1. A method of treating actinic keratosis, the method comprising applying topically to an actinic keratosis lesion twice per week for a duration of 8 weeks a formulation comprising:
0.3% by weight of 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine;
0.15% by weight sorbic acid;
5.0% by weight propylene glycol;
0.2% by weight methylparaben;
0.1% by weight butylated hydroxyanisole;
0.05% by weight ethylenediaminetetraacetic acid disodium salt dihydrate;
7.0% by weight isostearic acid;
4.0% by weight of caprylic/capric triglyceride;
1.0% by weight of a carbomer;
3.5% by weight of a poloxamer;
0.8% by weight of an aqueous solution of 20% by weight NaOH in water; and
77.9% by weight water;
wherein the weight percentages are based on the total weight of the formulation.
2. A method of treating actinic keratosis, the method comprising applying topically to an actinic keratosis lesion twice per week for a duration of 8 weeks a formulation comprising:
0.3% by weight of 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine;
0.1% by weight sorbic acid;
5.0% by weight propylene glycol;
0.2% by weight methylparaben;
0.01% by weight butylated hydroxyanisole;
0.05% by weight ethylenediaminetetraacetic acid disodium salt dihydrate;
7.0% by weight isostearic acid;
4.0% by weight of caprylic/capric triglyceride;
1.0% by weight of a carbomer;
3.5% by weight of a poloxamer;
0.8% by weight of an aqueous solution of 20% by weight NaOH in water; and
78.0% by weight water;
wherein the weight percentages are based on the total weight of the formulation.
3. A method of treating a patient diagnosed with actinic keratosis, the method comprising applying topically to a treatment area comprising at least one actinic keratosis lesion or pre-actinic keratosis lesion for a treatment cycle of at least twice per week for a duration of at least 4 weeks an effective amount of a formulation comprising:
0.3% by weight of 2-methyl-1-(2-methylpropyl)-1H-imidazo[4,5-c][1,5]naphthyridin-4-amine (sotirimod);
0.15% by weight sorbic acid;
5.0% by weight propylene glycol;
0.2% by weight methylparaben;
0.1% by weight butylated hydroxyanisole;
0.05% by weight ethylenediaminetetraacetic acid disodium salt dihydrate;
7.0% by weight isostearic acid;
4.0% by weight of caprylic/capric triglyceride;
1.0% by weight of a carbomer;
3.5% by weight of a poloxamer;
0.8% by weight of an aqueous solution of 20% by weight NaOH in water; and
77.9% by weight water;
wherein the weight percentages are based on the total weight of the formulation.
4. The method of claim 3 further comprising applying the formulation at least twice per week for eight weeks.
5. The method of claim 3 further comprising applying the formulation at least three times per week for four weeks.
6. The method of claim 3 further comprising applying the formulation at least three times per week for eight weeks.
7. The method of claim 3 , wherein the method comprises applying the formulation to the treatment area prior to sleeping hours.
8. The method of claim 3 , wherein the formulation, once applied to the lesion, is left on the treatment area for about 8 hours.
9. The method of claim 3 , wherein the formulation, once applied to the lesion, is left on the treatment area without occlusion.
10. The method of claim 3 , wherein the formulation is applied to the treatment area with rubbing.
11. The method of claim 3 , wherein prior to application, the treatment area is washed.
12. The method of claim 3 , wherein at least a portion of the treatment area is located on the patient's head.
13. The method of claim 12 , wherein at least a portion of the treatment area is located on the patient's face.
14. The method of claim 12 , wherein at least a portion of the treatment area is located on the patient's scalp.
15. The method of claim 3 , wherein the effective amount of the formulation comprises about 10 mg of the formulation applied to each square centimeter of the treatment area.
16. The method of claim 3 , wherein the effective amount of the formulation comprises about 250 mg of the formulation applied to 25 cm 2 of the treatment area.
17. The method of claim 3 , wherein the effective amount of the formulation comprises about 250 mg of the formulation.
18. The method of claim 3 , wherein the treatment area comprises about 25 cm 2 .
19. The method of claim 3 , wherein the method further comprises the step of:
Conducting a first follow-up visit at approximately 8 weeks post-treatment to assess the treatment site for clinical clearance.
20. The method of claim 19 , wherein clinical clearance comprises at least 75% reduction in actinic keratosis lesions or pre-actinic keratosis lesions.
21. The method of claim 19 , wherein the first follow-up visit further comprises assessment of the treatment site for erythema.
22. The method of claim 19 , wherein the clinical clearance comprises a response rate of at least about 58.1% for at least 75% reduction in actinic keratosis lesions or pre-actinic keratosis lesions at about 12 weeks after the four-week treatment cycle or a response rate of at least about 29.0% for 100% reduction in actinic keratosis lesions or pre-actinic keratosis lesions at about 8 weeks after the four-week treatment cycle.
23. The method of claim 19 , wherein the clinical clearance comprises a response rate of about 58.6% for at least 75% reduction in actinic keratosis lesions or pre-actinic keratosis lesions at about 12 weeks after the four-week treatment cycle or a response rate of about 41.4% for 100% reduction in actinic keratosis lesions or pre-actinic keratosis lesions at about 8 weeks after the four-week treatment cycle.
24. The method of claim 19 , wherein the treatment cycle comprises applying the formulation at least twice per week for eight weeks; and
wherein the clinical clearance comprises a response rate of at least about 69.0% for at least 75% reduction in actinic keratosis lesions or pre-actinic keratosis lesions at about 12 weeks after the eight-week treatment cycle or a response rate of at least about 55.2% for 100% reduction in actinic keratosis lesions or pre-actinic keratosis lesions at about 8 weeks after the eight-week treatment cycle.
25. The method of claim 19 , wherein the treatment cycle comprises applying the formulation at least twice per week for eight weeks; and
wherein the clinical clearance comprises a response rate of about 79.4% for at least 75% reduction in actinic keratosis lesions or pre-actinic keratosis lesions at about 12 weeks after the four-week treatment cycle or a response rate of about 64.7% for 100% reduction in actinic keratosis lesions or pre-actinic keratosis lesions at about 8 weeks after the four-week treatment cycle.
26. The method of claim 19 , wherein the first follow-up visit further comprises assessment of the treatment site for incidence of erythema.
27. The method of claim 25 , wherein the incidence of erythema is about 34.5% or less.
28. The method of claim 27 , wherein the incidence of erythema is about 6.5%.
29. The method of claim 25 , wherein the treatment cycle comprises applying the formulation at least twice per week for eight weeks; and
wherein the incidence of erythema is about 31.0% or less.
30. The method of claim 29 , wherein the incidence of erythema is about 8.8%.
31. The method of claim 3 , wherein the concentration of the sorbic acid in the formulation does not decrease by more than 15% of the initial concentration after the formulation is stored for at least 6 months at 40° C. and 75% relative humidity.