Titration package for neramexane and its use in the treatment of an inner ear disorder

Abstract

The present invention relates to a titration scheme for the administration of a 1-amino-alkylcyclohexane derivative which allows for quick attainment of an effective dose of a 1-amino-alkylcyclohexane derivative while minimizing side effects. The present invention further relates to a titration package for providing a 1-amino-alkylcyclohexane derivative (e.g., neramexane or a pharmaceutically acceptable salt thereof) in at least two different dosages. The present titration scheme/titration package may be useful in the treatment of various diseases, including tinnitus.

1 . A method of treating an inner ear disorder in a subject in need thereof, comprising administration of a 1-amino-alkylcyclohexane derivative selected from neramexane and pharmaceutically acceptable salts thereof, wherein the 1-amino-alkylcyclohexane derivative is administered in a titration scheme comprising up-titration of the 1-amino-alkylcyclohexane derivative in increasing dosages of 25 mg or 12.5 mg steps at weekly intervals. 
     
     
         2 . The method of  claim 1 , wherein the titration scheme comprises up-titration of the 1-amino-alkylcyclohexane derivative over a period of from four to five weeks. 
     
     
         3 . The method of  claim 1 , wherein the titration scheme comprises up-titration of the 1-amino-alkylcyclohexane derivative over a period of from four to five weeks to achieve an effective dose of from 5 to 150 mg per day or over a period of from four to five weeks to achieve an effective dose of from 50 to 75 mg per day. 
     
     
         4 . The method of  claim 1 , wherein the titration scheme comprises up-titration of the 1-amino-alkylcyclohexane derivative over a period of four weeks to achieve an effective dose of 50 mg per day. 
     
     
         5 . The method of  claim 4 , wherein the 1-amino-alkylcyclohexane derivative thereof is administered according to the following schedule: once daily at a dose of 12.5 mg per day for the first week, twice daily, wherein each dose is 12.5 mg for the second week, twice daily, wherein one dose is 12.5 mg and the other dose is 25 mg for the third week, and twice daily, wherein each dose is 25 mg for the fourth week. 
     
     
         6 . The method of  claim 5 , wherein in weeks during which mixed doses are administered, the dose comprising the higher concentration is administered in the second daily dose. 
     
     
         7 . The method of  claim 1 , wherein the titration scheme comprises up-titration of the 1-amino-alkylcyclohexane derivative over a period of five weeks to achieve an effective dose of 75 mg per day. 
     
     
         8 . The method of  claim 7 , wherein the 1-amino-alkylcyclohexane derivative is administered according to the following schedule: once daily at a dose of 12.5 mg per day for the first week, twice daily, wherein each dose is 12.5 mg for the second week, twice daily, wherein one dose is 12.5 mg and the other dose is 25 mg for the third week, twice daily, wherein each dose is 25 mg for the fourth week, and twice daily, wherein each dose is 37.5 mg for the fifth week. 
     
     
         9 . The method of  claim 8 , wherein in weeks during which mixed doses are administered, the dose comprising the higher concentration is administered in the second daily dose. 
     
     
         10 . The method of  claim 1 , wherein 1-amino-alkylcyclohexane derivative is neramexane mesylate. 
     
     
         11 . The method of  claim 1 , wherein the inner ear disorder is selected from tinnitus, vertigo, hearing loss, chronic ear pain, perilymphatic fistula, secondary endolymphatic hydrops, labyrinthitis and vestibular neuritis, acoustic neurome, ototoxicity, autoimmune inner ear diseases (AIED) and Meniere's disease. 
     
     
         12 . The method of  claim 11 , wherein the inner ear disorder is subjective or objective tinnitus and wherein the tinnitus may be in acute, sub-acute, or chronic form. 
     
     
         13 . The method of  claim 11 , wherein the inner ear disorder is cochlear tinnitus, tinnitus associated with hearing loss, or tinnitus associated with mild hearing loss. 
     
     
         14 . The method of  claim 1 , wherein the 1-amino-alkylcyclohexane derivative is provided in the form of a titration package for providing the 1-amino-alkylcyclohexane derivative in at least two different dosages. 
     
     
         15 . The method of  claim 1 , wherein the 1-amino-alkylcyclohexane derivative is administered according to the following schedule: once daily at a dose of 25 mg per day for the first week, once daily at a dose of 50 mg per day for the second week, and, optionally, once daily, at a dose of 75 mg per day for the third week. 
     
     
         16 . A titration package comprising a 1-amino-alkylcyclohexane derivative selected from neramexane and pharmaceutically acceptable salts thereof in at least two different dosages. 
     
     
         17 . The titration package of  claim 16 , wherein the 1-amino-alkylcyclohexane derivative is neramexane mesylate. 
     
     
         18 . The titration package of  claim 16 , which comprises the 1-amino-alkylcyclohexane derivative in at least two different dosages wherein the titration package comprises at least two sets of dosage forms of like dosage, each set comprises at least three individually addressable regions, and each addressable region comprises or is represented by the 1-amino-alkylcyclohexane derivative, including in form of a tablet. 
     
     
         19 . The titration package according to  claim 18 , wherein the at least three individually addressable regions within each set are arranged essentially along at least one horizontal line (defining a “row”) or are arranged essentially along at least one vertical line (defining a “column”). 
     
     
         20 . The titration package according to  claim 18 , wherein the at least three addressable regions of the at least two sets of dosage forms of like dosage are differentiated from each other by at least one means selected from the following group, or any combination thereof: highlighting by color and/or shading and/or imprint, provision of a blister pack at the position of the addressable region; provision of an identification/elevation; provision of a different material or a gradient in material, provision of a pouch or a blister or other conceivable containment for the 1-amino-alkylcyclohexane derivative. 
     
     
         21 . The titration package according to  claim 18 , wherein each set of dosage forms of like dosage comprises at least five addressable regions, including seven addressable regions or fourteen addressable regions. 
     
     
         22 . The titration package according to  claim 18 , wherein the titration package allows for an up- and/or down-titration of the dosage of the 1-amino-alkylcyclohexane derivative, until a certain final dosage level is reached.