Treatment of inflammatory lesions of rosacea with ivermectin

Abstract

Methods for safe and effective treatment of inflammatory lesions of rosacea in a subject are described. The methods involve once daily topically applying to an affected skin area a topical composition containing ivermectin and a pharmaceutically acceptable carrier. It has been demonstrated that once daily topical treatment with ivermectin is significantly superior than twice-daily topical treatment with metronidazole in reducing inflammatory lesion counts.

I/We claim: 
     
         1 . A method of treating inflammatory lesions of rosacea in a subject in need thereof, comprising topically administering, once daily, to a skin area affected by the inflammatory lesions of rosacea a therapeutically effective amount of a pharmaceutical composition comprising 1% by weight ivermectin and a pharmaceutically acceptable carrier, wherein there is no plasma accumulation of ivermectin over a 52-week treatment period. 
     
     
         2 . The method of  claim 1 , wherein a steady state of plasma concentration of ivermectin is reached in the subject 2 weeks after the initial administration of the pharmaceutical composition to the subject. 
     
     
         3 . The method of  claim 2 , wherein at the steady state, the highest mean (±standard deviation) plasma concentrations of ivermectin peak at 10±8 hours post-dose. 
     
     
         4 . The method of  claim 2 , wherein at the steady state, a mean C max  of ivermectin is 2.10±1.04 ng/mL with a range of 0.69-4.02 ng/mL, and a mean AUC 0-24hr  is 36.14±15.56 ng·hr/mL with a range of 13.69-75.16 ng·hr/mL. 
     
     
         5 . The method of  claim 1 , wherein the subject has moderate to severe papulopustular rosacea before the treatment. 
     
     
         6 . The method of  claim 5 , wherein the subject has 15 or more of the inflammatory lesions before the treatment. 
     
     
         7 . The method of  claim 1 , wherein the pharmaceutical composition further comprises one or more ingredients selected from the group consisting of: an oily phase comprising dimethicone, cyclomethicone, isopropyl palmitate and/or isopropyl myristate, the oily phase further comprising fatty substances selected from the group consisting of cetyl alcohol, cetostearyl alcohol, stearyl alcohol, palmitostearic acid, stearic acid and self-emulsifiable wax; at least one surfactant-emulsifier selected from the group consisting of glyceryl/PEG100 stearate, sorbitan monostearate, sorbitan palmitate, Steareth-20, Steareth-2, Steareth-21 and Ceteareth-20; a mixture of solvents and/or propenetrating agents selected from the group consisting of propylene glycol, oleyl alcohol, phenoxyethanol and glyceryl triacetate; one or more gelling agents selected from the group consisting of carbomers, cellulose gelling agents, xanthan gums, aluminum magnesium silicates but excluding aluminum magnesium silicate/titanium dioxide/silica, guar gums, polyacrylamides and modified starches; and water. 
     
     
         8 . The method of  claim 1 , wherein the pharmaceutical composition further comprises carbomer copolymer type B; cetyl alcohol; citric acid monohydrate; dimethicone 20 Cst; edetate disodium; glycerin; isopropyl palmitate; methyl paraben; oleyl alcohol; phenoxyethanol; polyoxyl 20 cetostearyl ether; propylene glycol; propyl paraben; purified water; sodium hydroxide; sorbitan monostearate and stearyl alcohol. 
     
     
         9 . A method of treating inflammatory lesions of rosacea in a subject in need thereof, comprising topically administering, once daily, to a skin area affected by the inflammatory lesions of rosacea a therapeutically effective amount of a pharmaceutical composition comprising 1% by weight ivermectin and a pharmaceutically acceptable carrier, wherein the treatment has a median time to first relapse of 110 days or longer. 
     
     
         10 . The method of  claim 9 , wherein a steady state of plasma concentration of ivermectin is reached in the subject 2 weeks after the initial administration of the pharmaceutical composition to the subject. 
     
     
         11 . The method of  claim 9 , wherein at the steady state, the highest mean (±standard deviation) plasma concentrations of ivermectin peak within 10±8 hours post-dose. 
     
     
         12 . The method of  claim 11 , wherein at the steady state, a mean C max  of ivermectin is 2.10±1.04 ng/mL with a range of 0.69-4.02 ng/mL, and a mean AUC 0-24hr  is 36.14±15.56 ng·hr/mL with a range of 13.69-75.16 ng·hr/mL. 
     
     
         13 . The method of  claim 9 , wherein the subject has moderate to severe papulopustular rosacea before the treatment. 
     
     
         14 . The method of  claim 9 , wherein the subject has 15 or more of the inflammatory lesions before the treatment. 
     
     
         15 . The method of  claim 9 , wherein the pharmaceutical composition further comprises one or more ingredients selected from the group consisting of: an oily phase comprising dimethicone, cyclomethicone, isopropyl palmitate and/or isopropyl myristate, the oily phase further comprising fatty substances selected from the group consisting of cetyl alcohol, cetostearyl alcohol, stearyl alcohol, palmitostearic acid, stearic acid and self-emulsifiable wax; at least one surfactant-emulsifier selected from the group consisting of glyceryl/PEG100 stearate, sorbitan monostearate, sorbitan palmitate, Steareth-20, Steareth-2, Steareth-21 and Ceteareth-20; a mixture of solvents and/or propenetrating agents selected from the group consisting of propylene glycol, oleyl alcohol, phenoxyethanol and glyceryl triacetate; one or more gelling agents selected from the group consisting of carbomers, cellulose gelling agents, xanthan gums, aluminum magnesium silicates but excluding aluminum magnesium silicate/titanium dioxide/silica, guar gums, polyacrylamides and modified starches; and water. 
     
     
         16 . The method of  claim 15 , wherein the pharmaceutical composition further comprises carbomer copolymer type B; cetyl alcohol; citric acid monohydrate; dimethicone 20 Cst; edetate disodium; glycerin; isopropyl palmitate; methyl paraben; oleyl alcohol; phenoxyethanol; polyoxyl 20 cetostearyl ether; propylene glycol; propyl paraben; purified water; sodium hydroxide; sorbitan monostearate and stearyl alcohol.