Cladribine regimen for treating progressive forms of Multiple Sclerosis

Abstract

Specific oral dosings, specific oral dosage forms, and/or specific oral dose regimens including Cladribine can be effective for the treatment of progressive forms of Multiple Sclerosis, especially Primary Progressive Multiple Sclerosis and/or Secondary Progressive Multiple Sclerosis. Methods of treatment can be based on specific oral dosings, specific oral dosage forms, and/or specific oral dose regimens including Cladribine.

1 - 71 . (canceled) 
     
     
         72 : A method of treating Secondary Progressive Multiple Sclerosis (SPMS), said method comprising:
 orally administering Cladribine to a patient in need thereof at a fixed administered dose, and   achieving an effective fixed dose in said patient in a range of 0.6 mg/kg to 1.6 mg/kg per patient, per body weight and per treatment year.   
     
     
         73 : The method according to  claim 72 , wherein said effective fixed dose achieved in said patient is about 0.7 mg/kg or about 1.4 mg/kg per patient, per body weight and per treatment year. 
     
     
         74 : The method according to  claim 73 , wherein said effective fixed dose achieved in said patient is 0.7 mg/kg per patient, per body weight and per treatment year with a maximum deviation of +/−0.08 mg/kg. 
     
     
         75 : The method according to  claim 72 , wherein said Cladribine is orally administered in the form of one or more Cladribine containing tablets or capsules to the patient in need thereof at said fixed administered dose,
 i) wherein said fixed administered dose of Cladribine provided by said one or more tablets or capsules is in a range of 1.5 mg/kg to 4.0 mg/kg per patient, per body weight and per treatment year, and   ii) wherein a bioavailability of said fixed administered dose of Cladribine in said one or more tablets or capsules is about 40%.   
     
     
         76 : The method according to  claim 72 , wherein said Cladribine is orally administered in the form of one or more Cladribine containing tablets or capsules to the patient in need thereof at said fixed administered dose,
 i) wherein said fixed administered dose of Cladribine provided by said one or more tablets or capsules is about 175 mg/kg per patient, per body weight and per treatment year, and   ii) wherein a bioavailability of said fixed administered dose of Cladribine in said one or more tablets or capsules is about 40%.   
     
     
         77 : The method according to  claim 72 , wherein said effective fixed dose in said patient is achieved by orally administering one or more Cladribine containing tablets or capsules to said patient within two adjacent months within said treatment year. 
     
     
         78 : The method according to  claim 77 , wherein said effective fixed dose in said patient is achieved by orally administering said one or more Cladribine containing tablets or capsules to said patient within one week or two adjacent weeks at the beginning of each of said two adjacent months. 
     
     
         79 : The method according to  claim 78 , wherein said effective fixed dose in aid patient is achieved by orally administering said one or more Cladribine containing tablets or capsules to said patient within 4 to 5 days during said one week, or within 4 to 5 days of each of said two adjacent weeks. 
     
     
         80 : The method according to  claim 72 , wherein said Cladribine is orally administered for at least two or at least three treatment years. 
     
     
         81 : The method according to  claim 72 , wherein each treatment year comprises:
 (i) a treatment period of 2 months at the beginning of said treatment year, wherein said effective fixed dose of Cladribine in said patient is achieved by administering Cladribine containing tablets or capsules orally on 3 to 5 days each month at the beginning of each month, wherein said tablets or capsules provide for the oral administration of daily doses of about 10 mg or of about 20 mg of Cladribine, and   (ii) a Cladribine-free period lasting at least about 8 months or lasting at least about 10 months, during which no Cladribine is administered.   
     
     
         82 : The method according to  claim 81 , wherein said patient suffers from Secondary Progressive Multiple Sclerosis, wherein said effective fixed dose achieved per patient, per body weight and per treatment year is 0.7 mg/kg per treatment year with a maximum deviation of +/−0.2 mg/kg, and wherein orally administering said Cladribine comprises at least two treatment years. 
     
     
         83 : The method according to  claim 81 , wherein treatment comprises two treatment years in which Cladribine is orally administered at a fixed administered dose to said patient,
 wherein a cumulative fixed administered dose of Cladribine to be orally administered to said patient during said two treatment years is about 3.5 mg/kg body weight, and   wherein said fixed administered dose is about 1.75 mg/kg per treatment year.   
     
     
         84 : The method according to  claim 81 , wherein treatment comprises two treatment years in which Cladribine is orally administered, and
 wherein a cumulative effective fixed dose of Cladribine to be achieved in said patient during said two treatment years is about 1.4 mg/kg body weight, and   wherein the effective fixed dose of Cladribine to be achieved in said patient during each of the two treatment years is about 0.7 mg/kg per treatment year.   
     
     
         85 : The method according to  claim 81 , wherein said Cladribine is orally administered as a tablet or a capsule. 
     
     
         86 : The method according to  claim 85 , wherein said Cladribine is orally administered at a daily dose of about 3 to 30 mg Cladribine, of about 5 to 20 mg Cladribine, or of about 10 mg or about 20 mg of Cladribine. 
     
     
         87 : A method of treating a patient diagnosed as suffering from Secondary Progressive Multiple Sclerosis, said method comprising:
 orally administering to said patient a cumulative administered fixed dose of Cladribine of about 3.5 mg/kg body weight, with a maximum deviation of +/−0.4 mg/kg, over 2 years, administered in each year as 1 treatment course of about 1.75 mg/kg+/−0.2 mg/kg per year,   wherein each treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year.   
     
     
         88 : The method according to  claim 87 , wherein said Cladribine is orally administered in the form of one or more Cladribine containing tablets or capsules to the patient in need thereof,
 wherein a bioavailability of said Cladribine in said one or more tablets or capsules is in the range from 30% to 50%, or is about 40%.   
     
     
         89 : The method according to  claim 87 , wherein each treatment week consists of 4 or 5 days on which said patient receives 10 mg or 20 mg of Cladribine for oral administration, depending on the body weight of said patient. 
     
     
         90 : A method of treating a patient diagnosed as suffering from Secondary Progressive Multiple Sclerosis, said method comprising:
 orally administering one or more Cladribine containing tablets or capsules to said patient in a manner that the cumulative effective dose of Cladribine achieved in said patient is about 1.4 mg/kg body weight over 2 years,   administered in each year as 1 treatment course thereby achieving an effective dose of Cladribine in said patient of about 0.7 mg/kg per year,   wherein each treatment course consists of 2 treatment weeks, one at the beginning of the first month and one at the beginning of the second month of the respective treatment year.   
     
     
         91 : The method according to  claim 90 , wherein
 i) said effective cumulative dose of Cladribine of about 1.4 mg/kg body weight in said patient over said 2 years is achieved by orally administering Cladribine containing tablets or capsules to said patient, wherein each treatment week consists of 4 or 5 days on which said patient receives 10 mg or 20 mg of Cladribine for oral administration, depending on the body weight of said patient;   and/or   ii) said effective dose of Cladribine of about 0.7 mg/kg body weight in said patient in each year is achieved by orally administering Cladribine containing tablets or capsules to said patient as 1 treatment course, wherein each treatment week consists of 4 or 5 days on which said patient receives 10 mg or 20 mg of Cladribine for oral administration, depending on the body weight of said patient.   
     
     
         92 : The method according to  claim 90 , wherein the patient additionally receives at least one disease modifying drug other than Cladribine. 
     
     
         93 : The method according to  claim 92 , wherein said at least one disease modifying drug other than Cladribine is an interferon selected from the group consisting of Interferon beta-1a, Beta interferon-1a, Interferon beta-1b, Beta interferon-1b, and Peginterferon beta 1a. 
     
     
         94 : The method according to  claim 90 , wherein after the completion of said 2 years with said 2 treatment courses, no Cladribine is administered to the patient in the subsequent 1 or 2 years following the completion of said 2 years with said 2 treatment courses. 
     
     
         95 : A method of treating a patient suffering from Secondary Progressive Multiple Sclerosis (SPMS), comprising:
 orally administering to said patient tablets or capsules containing about 10 mg of Cladribine each, wherein said tablets or capsules are administered during a first treatment year comprising the following regimen:   (i) a first treatment course lasting 2 months, wherein the Cladribine tablets or capsules are orally administered daily at a daily dose of 10 or 20 mg of Cladribine on a treatment week of from 3 to up to 6 days each month;   (ii) followed by a Cladribine-free period lasting at least 8 or at least 10 months wherein no Cladribine is administered to said patient;   wherein patients having a bodyweight   in the range of 40 to less than 50 kg are administered
 1) 4 tablets or capsules (40 mg of Cladribine) in the 1st treatment week of said treatment course, 
 2) 4 tablets or capsules (40 mg of Cladribine) in the 2nd treatment week of said treatment course; 
   in the range of 50 to less than 60 kg are administered
 1) 5 tablets or capsules (50 mg of Cladribine) in the 1st treatment week of said treatment course, respectively, 
 2) 5 tablets or capsules (50 mg of Cladribine) in the 2nd treatment week of said treatment course; 
   in the range of 60 to less than 70 kg are administered
 1) 6 tablets or capsules (60 mg of Cladribine) in the 1st treatment week of said treatment course, 
 2) 6 tablets or capsules (60 mg of Cladribine) in the 2nd treatment week of said treatment course; 
   in the range of 70 to less than 80 kg are administered
 1) 7 tablets or capsules (70 mg of Cladribine) in the 1st treatment week of said treatment course, 
 2) 7 tablets or capsules (70 mg of Cladribine) in the 2nd treatment week of said treatment course; 
   in the range of 80 to less than 90 kg are administered
 1) 8 tablets or capsules (80 mg of Cladribine) in the 1st treatment week of said treatment course, 
 2) 7 tablets or capsules (70 mg of Cladribine) in the 2nd treatment week of said treatment course; 
   in the range of 90 to less than 100 kg are administered
 1) 9 tablets or capsules (90 mg of Cladribine) in the 1st treatment week of said treatment course, 
 2) 8 tablets or capsules (80 mg of Cladribine) in the 2nd treatment week of said treatment course; 
   in the range of 100 to less than 110 kg are administered
 1) 10 tablets or capsules (100 mg of Cladribine) in the 1st treatment week of said treatment course, 
 2) 9 tablets or capsules (90 mg of Cladribine) in the 2nd treatment week of said treatment course; or 
   in the range of 110 kg and above are administered
 1) 10 tablets or capsules (100 mg of Cladribine) in the 1st treatment week of said treatment course, 
 2) 10 tablets or capsules (100 mg of Cladribine) in the 2nd treatment week of said treatment course. 
   
     
     
         96 : The method according to  claim 95 , wherein the method further comprises a second treatment year, wherein said second treatment year comprises a second treatment course substantially identical to said first treatment course, and a subsequent Cladribine-free period lasting at least 10 months wherein no Cladribine is administered to said patient. 
     
     
         97 : The method according to  claim 95 , wherein a bioavailability of said Cladribine in said tablets or capsules is in the range from 30% to 50%, or is about 40%. 
     
     
         98 : The method according to  claim 96 , wherein said second treatment year is directly adjacent to said first treatment year, or wherein the method comprises a gap of 1 to 10 months in between the two treatment years. 
     
     
         99 : The method according to  claim 95 , wherein a bioavailability of said Cladribine in said tablet or capsule is in the range from 30% to 50%, or is about 40%. 
     
     
         100 : The method according to claim  106 , wherein to the patient having completed said 2 treatment courses of one year each, no further Cladribine treatment is administered to said patients in the subsequent years 3 and 4. 
     
     
         101 : The method according to  claim 72 , wherein said Secondary Progressive Multiple Sclerosis does not include Early Secondary Progressive Multiple Sclerosis (ESPMS).