Dosing regimen for a selective s1p1 receptor agonist

Abstract

The present invention relates to a dosing regimen for a selective S1P1 receptor agonist, whereby the selective S1P1 receptor agonist is administered to a subject in such a way that during the initial treatment phase the selective S1P1 receptor agonist is administered at a dose which induces desensitization of the heart wherein said dose is below the target dose, and at a dosing frequency that sustains desensitization of the heart, until no further acute heart rate reduction occurs, followed by dose up-titration to the target dose of the selective S1P1 receptor agonist.

1 . A selective S1P 1  receptor agonist for use as a medicament, whereby said selective S1P 1  receptor agonist is administered to a subject in such a way that during the initial treatment phase the selective S1P 1  receptor agonist is administered at a dose which induces desensitization of the heart wherein said dose is below the target dose, and at a dosing frequency that sustains desensitization of the heart, until no further acute heart rate reduction occurs, followed by dose up-titration to the target dose of the selective S1P 1  receptor agonist. 
     
     
         2 . The selective S1P 1  receptor agonist for use as a medicament according to  claim 1 , whereby the initial dose below the target dose is between 2- to 5-fold lower than the target dose. 
     
     
         3 . The selective S1P 1  receptor agonist for use as a medicament according to  claim 1 , whereby the initial dose below the target dose is between 5- to 16-fold lower than the target dose. 
     
     
         4 . The selective S1P 1  receptor agonist for use as a medicament according to any one of  claims 1  to  3 , whereby a dose below the target dose is administered to the subject during the initial 2 to 4 days of the treatment. 
     
     
         5 . The selective S1P 1  receptor agonist for use as a medicament according to any one of  claims 1  to  4 , whereby the dose below the target dose is administered at a dosing frequency of once or twice daily. 
     
     
         6 . The selective S1P 1  receptor agonist for use as a medicament according to any one of  claims 1  to  5 , wherein the selective S1P 1  receptor agonist is (R)-5-[3-chloro-4-(2,3-dihydroxy-propoxy)-benz[Z]ylidene]-2-([Z]-propylimino)-3-o-tolyl-thiazolidin-4-one, or a pharmaceutically acceptable salt thereof. 
     
     
         7 . Use of a selective S1P 1  receptor agonist in the manufacture of a medicament, whereby said medicament is administered to a subject as specified in any one of  claims 1  to  5 . 
     
     
         8 . The use according to  claim 7 , wherein the selective S1P 1  receptor agonist is (R)-5-[3-chloro-4-(2,3-dihydroxy-propoxy)-benz[Z]ylidene]-2-([Z]-propylimino)-3-o-tolyl-thiazolidin-4-one, or a pharmaceutically acceptable salt thereof. 
     
     
         9 . A kit containing different units of medication of a selective S1P 1  receptor agonist for administration according to  claim 1 , whereby one or more units of a dose strength below the target dose of said selective S1P 1  receptor agonist are provided for the initial treatment phase, and subsequent units of medication of higher dose strengths up to the target dose of said selective S1P 1  receptor agonist are provided. 
     
     
         10 . The kit according to  claim 9 , wherein the selective S1P 1  receptor agonist is (R)-5-[3-chloro-4-(2,3-dihydroxy-propoxy)-benz[Z]ylidene]-2-([Z]-propylimino)-3-o-tolyl-thiazolidin-4-one, or a pharmaceutically acceptable salt thereof. 
     
     
         11 . The kit according to  claim 9  or  10 , whereby subsequent units of medication of 2- to 5-fold higher dose strengths compared to the initial dose strength are provided. 
     
     
         12 . The kit according to  claim 9  or  10 , whereby subsequent units of medication of 5- to 16-fold higher dose strengths compared to the initial dose strength are provided. 
     
     
         13 . The kit according to any one of  claims 9  to  12 , whereby the dose strength units below the target dose are provided for the initial 2 to 4 days of treatment. 
     
     
         14 . The kit according to any one of  claims 9  to  13 , whereby the dose strength unit(s) below the target dose is/are administered at a dosing frequency of once or twice daily.