Claims for Patent: 11,857,528

Summary for Patent: 11,857,528

Title:	Methods of providing solriamfetol therapy to subjects with impaired renal function
Abstract:	The invention relates to methods for decreasing adverse effects associated with solriamfetol ([R]-2-amino-3-phenylpropylcarbamate) therapy in subjects with impaired renal function. In particular, the invention provides an optimized dose escalation scheme for subjects with moderate renal impairment which results in the subjects having increased tolerance to adverse effects associated with the administration of solriamfetol. The invention also provides adjusted dosing for safe therapeutic use of solriamfetol in subjects having severe renal impairment.
Inventor(s):	Katayoun Zomorodi
Assignee:	Axsome Malta Ltd
Application Number:	US18/340,006
Patent Claims:	1. A method of treating excessive daytime sleepiness in a subject in need thereof having mild, moderate, or severe renal impairment, said method comprising: (a) providing to the subject having an eGFR of about 30 mL/min/1.73 m2 to about 59 mL/min/1.73 m2: a first oral daily dose equivalent to 37.5 mg [R]-2-amino-3-phenylpropylcarbamate (APC) from day one to day n1 of a dose escalation regimen, and a second oral daily dose equivalent to 75 mg APC starting on day n2 of the dose escalation regimen, wherein n1 is an integer equal to or greater than 5 and n2 is equal to the sum of n1+1, wherein the subject is not provided a daily dose exceeding a dose equivalent to 75 mg APC, and wherein the APC does not produce an AUC∞ greater than 2.3 times the AUC∞ for a subject without renal impairment; (b) providing to the subject having an eGFR of about 15 mL/min/1.73 m2 to about 29 mL/min/1.73 m2: an oral daily dose equivalent to 37.5 mg APC, wherein the subject is not provided a daily dose exceeding a dose equivalent to 37.5 mg APC, and wherein the APC does not produce an AUC∞ greater than 4.4 times the AUC∞ for a subject without renal impairment; or (c) providing to the subject having an eGFR of about 60 mL/min/1.73 m2 to about 89 mL/min/1.73 m2: a first oral daily dose equivalent to 37.5 mg APC, after at least 3 days a second oral daily dose equivalent to 75 mg APC, and after at least 3 days a third oral daily dose equivalent to 150 mg APC, wherein the subject is not provided a daily dose exceeding a dose equivalent to 150 mg APC, and wherein the APC does not produce an AUC∞ greater than 1.5 times the AUC∞ for a subject without renal impairment. 2. The method of claim 1, wherein the excessive daytime sleepiness is due to narcolepsy. 3. The method of claim 1, wherein the excessive daytime sleepiness is due to obstructive sleep apnea. 4. The method of claim 1, wherein the excessive daytime sleepiness is due to shift work disorder. 5. The method of claim 1, wherein the subject is provided said first oral daily dose or said oral daily dose in a form of about 44.7 mg APC-HCl. 6. The method of claim 1, wherein the subject is provided said second oral daily dose in a form of about 89.3 mg APC-HCl. 7. The method of claim 1, wherein the subject is provided said third oral daily dose in a form of about 178.5 mg APC-HCl. 8. The method of claim 1, wherein said first oral daily dose, said second oral daily dose, said third daily dose, and said oral daily dose are each administered upon the subject's awakening. 9. The method of claim 1, wherein said first oral daily dose, said second oral daily dose, said third daily dose, and said oral daily dose are each administered more than nine hours in advance of the subject's bedtime. 10. The method of claim 1, wherein the subject is a human. 11. The method of claim 1, wherein the eGFR is determined using a Modification in Diet in Renal Disease equation. 12. The method of claim 1, wherein n1 is an integer equal to or greater than 7. 13. A method of treating excessive daytime sleepiness in a subject in need thereof having mild, moderate, or severe renal impairment, said method comprising: (a) providing to the subject having an eGFR of about 30 mL/min/1.73 m2 to about 59 mL/min/1.73 m2 an oral daily dose of [R]-2-amino-3-phenylpropylcarbamate (APC) that does not produce an AUC∞, for APC greater than 2.3 times the AUC∞ for a subject without renal impairment; (b) providing to the subject having an eGFR of about 15 mL/min/1.73 m2 to about 29 mL/min/1.73 m2 an oral dose of APC that does not produce an AUC∞ greater than 4.4 times the AUC∞ for a subject without renal impairment; or (c) providing to the subject having an eGFR of about 60 mL/min/1.73 m2 to about 89 mL/min/1.73 m2 an oral daily dose of APC that does not produce an AUC∞ greater than 1.5 times the AUC∞ for a subject without renal impairment. 14. The method of claim 13, wherein the excessive daytime sleepiness is due to narcolepsy. 15. The method of claim 13, wherein the excessive daytime sleepiness is due to obstructive sleep apnea. 16. The method of claim 13, wherein the excessive daytime sleepiness is due to shift work disorder. 17. The method of claim 13, wherein the subject is provided said oral daily dose in a form of about 44.7 mg APC-HCl. 18. The method of claim 13, wherein the subject is provided said oral daily dose in a form of about 89.3 mg APC-HCl. 19. The method of claim 13, wherein the subject is provided said oral daily dose in a form of about 178.5 mg APC-HCl. 20. The method of claim 13, wherein said oral daily dose is administered upon the subject's awakening. 21. The method of claim 13, wherein said oral daily dose is administered more than nine hours in advance of the subject's bedtime. 22. The method of claim 13, wherein the subject is a human. 23. The method of claim 13, wherein the eGFR is determined using a Modification in Diet in Renal Disease equation. 24. The method of claim 13, wherein n1 is an integer equal to or greater than 7. 25. The method of claim 1, wherein the excessive daytime sleepiness is due to depression. 26. The method of claim 13, wherein the excessive daytime sleepiness is due to depression.