Claims for Patent: 11,090,312

Summary for Patent: 11,090,312

Title:	Methods of treating hypogonadism with transnasal testerosterone bio-adhesive gel formulations in male with allergic rhinitis, and methods for preventing an allergic rhinitis event
Abstract:	The present invention relates to methods of treating hypogonadism in a male subject through administering intranasally to the male subject an intranasal testosterone bio-adhesive gel formulation to deliver a therapeutically effective amount of testosterone. In particular, the testosterone therapy of the invention remains effective if an allergic rhinitis event occurs in the male during the treatment or when the male subject uses a topical nasal vasoconstrictor or a topical intranasal decongestant during the hypogonadism treatment. Further, the present invention relates to a method of preventing the occurrence of an allergic rhinitis event in a male, who is undergoing a hypogonadism treatment with an intranasal testosterone bio-adhesive gel. In certain embodiments, the intranasal testosterone bio-adhesive gel formulation according to the invention comprises 4.0% and 4.5% testosterone.
Inventor(s):	Natalia Tkachenko
Assignee:	Acerus Biopharma Inc
Application Number:	US16/905,610
Patent Claims:	1. A nasal method of treating a male with nasal testosterone replacement therapy for a condition associated with a deficiency or absence of endogenous testosterone, wherein the male suffers with symptomatic rhinitis and is in a symptomatic state for the rhinitis and the condition is hypogonadism and the hypogonadal male is in need of the nasal testosterone replacement therapy to treat the male's hypogonadism while being in the symptomatic state for rhinitis, the method comprising: (a) applying daily an individual dose of a nasal testosterone gel into the nose of the hypogonadal male three times a day for administering into the hypogonadal male's nose three individual doses of testosterone for intranasal absorption of the testosterone to deliver to the hypogonadal male an effective total daily dose of testosterone to produce a daily total 24-hour Cavg testosterone serum concentration that is ≥300 ng/dL to effectively treat the male's hypogonadism with the daily nasal testosterone replacement therapy; and (b) nasally administering oxymetazoline into the nostrils of the nose of the hypogonadal male who is in the symptomatic state for rhinitis for inducing arteriole vasoconstriction in the nostrils of the nose of the hypogonadal male to relieve the hypogonadal male's rhinitis symptoms, wherein the nasal arteriole vasoconstriction induced by the oxymetazoline does not impact the intranasal testosterone absorption from the nasal testosterone gel to any relevant extent that would impact or interfere with the effective daily nasal testosterone replacement therapy of the male's hypogonadism; wherein, the nostrils are left and right nostrils; and wherein, the intranasal gel contains about 4.5% testosterone by weight and a pharmaceutical vehicle. 2. A daily nasal method of treating a male, who is symptomatic with seasonal or allergic rhinitis, with nasal testosterone replacement therapy for a condition associated with a deficiency or absence of endogenous testosterone, wherein the condition is hypogonadism and the hypogonadal male is in need of the nasal testosterone replacement therapy to treat the male's hypogonadism, the method comprising: nasally applying individual doses of a nasal testosterone gel comprised of 4.5% testosterone by weight and a pharmaceutical vehicle into each nostril of the hypogonadal male's nose daily, who is symptomatic with a congested nose caused by the seasonal or allergic rhinitis, three times a day for intranasal absorption of the testosterone applied into the congested nose of the hypogonadal male to deliver to the hypogonadal male an effective total daily dose of testosterone of about 33 mg to effectively treat daily the hypogonadism of the hypogonadal male; wherein, each of the individual doses delivers about 11 mg of testosterone into the congested nose of the hypogonadal male, wherein about 5.5 mg of testosterone is delivered into each nostril; and wherein, the congested nose of the hypogonadal male does not relevantly affect the nasal absorption of the testosterone, so that the hypogonadism of the hypogonadal male can be effectively treated daily with the nasal testosterone replacement therapy. 3. A method of claim 1, wherein, the three individual daily doses of the 4.5% nasal testosterone gel total about 0.750 g in amount which collectively comprises about 33 mg of testosterone to deliver to the nose of the hypogonadal male the effective total daily dose; and wherein, each said individual dose of the 4.5% nasal testosterone gel is about 0.250 g in amount and about 11 mg of testosterone. 4. A method of claim 3, said method comprises the further step of: applying each said individual dose of the 4.5% nasal testosterone gel to the nose of the hypogonadal male as divided doses, wherein each divided dose contains about 5.5 mg of testosterone, wherein one said divided dose is applied to the right nostril of the nose of the hypogonadal male to deliver intranasally about 5.5 mg of testosterone for the intranasal testosterone absorption, wherein the other said divided dose is applied to the left nostril of the nose of the hypogonadal male to deliver intranasally about 5.5 mg of testosterone for the intranasal testosterone absorption, so that each said individual dose of about 11 mg of testosterone is delivered to the nose of the hypogonadal male for intranasal testosterone absorption of each said individual dose. 5. A method of claim 4, wherein each said individual dose is about 0.250 g in amount and each said divided dose is about 0.125 g. 6. A method of claim 1, wherein, the effective total daily dose of testosterone is about 33 mg, each said individual dose comprises about 11 mg of testosterone, and, when each said individual dose is nasally applied as divided doses into the left and right nostrils of the nose of the hypogonadal male, each said divided dose of testosterone comprises about 5.5 mg. 7. An intranasal testosterone method of treating a male daily, who experiences symptomatic allergic or seasonal rhinitis, with nasal testosterone replacement therapy for a condition associated with a deficiency or absence of endogenous testosterone, wherein the condition is hypogonadism and the rhinitis symptomatic male is in need of the nasal testosterone replacement therapy to treat his hypogonadism, the method comprising: administering intranasally testosterone gel to the rhinitis symptomatic male an intranasal dose of about 11 mg of testosterone three times a day to deliver to the rhinitis symptomatic male a total daily dose of about 33 mg of testosterone to produce a serum total testosterone concentration in the rhinitis symptomatic male of between about 300 ng/dL to about 1,050 ng/dL to treat the rhinitis symptomatic male for the hypogonadism; wherein, the testosterone is in an intranasal gel; wherein, the intranasal testosterone gel comprises about 4.5% testosterone by weight and a pharmaceutically acceptable vehicle; wherein, when the intranasal testosterone gel is administered intranasally in combination with a nasal vasoconstrictor and/or a nasal decongestant in the nose of the rhinitis symptomatic male and said nasal vasoconstrictor and/or said nasal decongestant does not interfere with the intranasal absorption of the testosterone, so that the rhinitis symptomatic male can be concurrently treated with the nasal testosterone replacement therapy to effectively treat daily the hypogonadism. 8. The intranasal testosterone method of claim 7, wherein the intranasal method includes the further step of: intranasally administering to the symptomatic male said nasal vasoconstrictor and/or said nasal decongestant to intranasally treat the symptomatic male with a combination of the testosterone gel and the nasal vasoconstrictor and/or nasal decongestant. 9. The intranasal testosterone method of claim 8, wherein said nasal vasoconstrictor or said nasal decongestant comprises a therapeutic agent selected from the group of ephedrine, levomethamphetamine, aphazoline, oxymetazoline, phenylephrine, pseudoephedrine, tramazoline, and xylometazoline. 10. The intranasal testosterone method of claim 8, wherein the nasal vasoconstrictor or the nasal decongestant comprises oxymetazoline. 11. The intranasal testosterone method of claim 10, wherein the intranasal oxymetazoline method step comprises administering the oxymetazoline intranasally prior to or concurrently with said intranasal testosterone administration. 12. The nasal testosterone method of claim 1, wherein said intranasal testosterone gel further comprises an oil-based solvent, a wetting agent, and a viscosity increasing agent. 13. The nasal testosterone method of claim 12, wherein the oil-based solvent is castor oil. 14. The nasal testosterone method of claim 12, wherein said wetting agent is an oleoyl polyoxylglyceride. 15. The nasal testosterone method of claim 12, wherein said viscosity increasing agent is colloidal silicon dioxide. 16. The intranasal testosterone method of claim 7, wherein the pharmaceutically acceptable vehicle comprises castor oil, oleoyl polyoxylglycerides and colloidal silicon dioxide. 17. The nasal testosterone method of claim 1, wherein the hypogonadal male has a testosterone Cavg within the normal testosterone range of 300 to 1050 ng/dL on or after day 90 of said nasal testosterone replacement therapy. 18. The intranasal testosterone method of claim 7, wherein the rhinitis symptomatic male has a testosterone Cavg within the normal testosterone range of 300 to 1050 ng/dL on or after day 90 of said intranasal testosterone treatment. 19. The nasal testosterone method of claim 1, wherein the hypogonadal male does not have a testosterone Cmax of greater than 2500 ng/dL on or after day 90 of said testosterone treatment. 20. The intranasal testosterone method of claim 7, wherein the rhinitis symptomatic male does not have a testosterone Cmax of greater than 2500 ng/dL on or after day 90 of said intranasal testosterone treatment. 21. The nasal testosterone method of claim 1, wherein said nasal testosterone gel has a testosterone rate of diffusion of between about 28 to about 100 slope/mgT %. 22. The nasal testosterone method of claim 21, wherein said testosterone diffusion rate is between about 30 to about 95 slope/mgT %. 23. The nasal testosterone method of claim 21, wherein said testosterone diffusion rate is between about 28 to about 35 slope/mgT %. 24. The intranasal testosterone method of claim 7, wherein said intranasal testosterone gel has a testosterone rate of diffusion of between about 28 to about 100 slope/mgT %. 25. The intranasal testosterone method of claim 24, wherein said testosterone diffusion rate is between about 30 to about 95 slope/mgT %. 26. The intranasal testosterone method of claim 24, wherein said testosterone diffusion rate is between about 28 to about 35 slope/mgT %. 27. The nasal testosterone method of claim 1, wherein the pharmaceutical vehicle comprises, 87.5% castor oil, 4.0% oleoyl polyoxylglycerides, and 4.0% colloidal silicon dioxide. 28. An intranasal testosterone method for treating a male with nasal testosterone replacement therapy for a condition associated with a deficiency or absence of endogenous testosterone who experiences symptomatic allergic or seasonal rhinitis and who in a symptomatic state and is in need of said nasal testosterone replacement therapy to treat the condition, said method comprising: providing a metered dose pump containing 11 grams of an intranasal testosterone gel, wherein the metered dose pump dispenses 60 metered pump actuations of an intranasal testosterone gel for treating the condition; and instructing the symptomatic male to actuate daily one pump from the metered dose pump into each of the symptomatic male's nostrils three times a day to deliver intranasally to the symptomatic male a total daily dose of about 33 mg of testosterone to effectively daily treat the symptomatic male for the condition; wherein, the one pump actuation delivers 5.5 mg of the testosterone in about 0.125 grams of the intranasal testosterone gel into each of the symptomatic male's nostrils; wherein, the condition is hypogonadism; wherein, the hypogonadism is selected from a group of hypogonadisms consisting of congenital or acquired primary hypogonadism and congenital or acquired hypogonadotropic hypogonadism; and wherein, the symptomatic male's hypogonadism is effectively treated with said nasal testosterone replacement therapy, whether or not the symptomatic state of the symptomatic male is untreated or treated with a nasal decongestant, whereby, neither the symptomatic state nor the decongestant relevantly affects the nasal absorption of the testosterone or interferes with the effective treatment of the symptomatic male's hypogonadism.