Methods of administering deflazacort therapy

Abstract

The disclosure provides a deflazacort therapy comprising, administering to a subject suffering from Duchenne muscular dystrophy (DMD) a fixed dose of deflazacort. Also provided is a deflazacort therapy comprising, increasing the deflazacort dosage when the subject loses ambulation; or, increasing the dosage of deflazacort administered during concomitant administration of a CYP3A4 inducer; or, decreasing the dosage of deflazacort administered during concomitant administration of a CYP3A inhibitor.

What is claimed: 
     
         1 . A deflazacort therapy for administration to a subject that is suffering from Duchenne muscular dystrophy (DMD) comprising,
 determining a fixed target dose range of deflazacort to be administered to the subject using one or more factors selected from the subject's age, weight and ambulatory status;   wherein the subject's age is selected from an age less than or equal to 11 years of age, an age greater than 11 years to less than or equal to 18 years of age or an age greater than 18 years of age,   wherein the subject's weight is selected from a weight less than or equal to 30 kg, a weight greater than 30 kg to less than or equal to 50 kg or a weight greater than 50 kg,   wherein the subject's ambulatory status is selected from ambulatory or non-ambulatory, and   wherein the selection of factors determine the fixed target dose range to administer;   administering a target dose from the fixed target dose range; and   measuring a treatment, amelioration or prevention of DMD symptoms selected from improved muscle strength, response time to a timed function test and improvement in pulmonary function in the subject.   
     
     
         2 . The method of  claim 1 , wherein the subject age range is less than or equal to 11 years of age and the fixed target dose range of deflazacort is 6-36 mg per day, having a target dose of 18 or 24 mg per day; or, the age range is greater than 11 years of age and less than or equal to 18 years of age and the fixed target dose range of deflazacort is 30-72 mg per day, having a target dose of 36, 42 or 48 mg per day; or, an age range of greater than 18 years of age and the fixed target dose range of deflazacort is 36-72 mg per day, having a target dose of 36, 42, 48, 54, 60 or 66 mg per day. 
     
     
         3 . The method of  claim 2 , wherein the fixed target dose range of deflazacort for a subject less than or equal to 11 years of age is selected from 6-18 mg per day, having a target dose of 18 mg per day for an ambulatory subject or, 12-30 mg per day, having a target dose of 18 or 24 mg per day for a non-ambulatory subject; or, wherein the fixed target dose range of deflazacort for a subject greater than 11 years of age and less than or equal to 18 years of age is selected from 30-60 mg per day, having a target dose of 36 mg per day for an ambulatory subject or, 36-72 mg per day, having a target dose of 36 or 42 mg per day for a non-ambulatory subject; or, wherein the fixed target dose range of deflazacort for a subject greater than 18 years of age is selected from 36-72 mg per day, having a target dose of 42 mg per day for an ambulatory subject or, 48-96 mg per day, having a target dose of 54 or 66 mg per day for a non-ambulatory subject. 
     
     
         4 . The method of  claim 1 , wherein the subject weight range is less than or equal to 30 kg and the fixed target dose range of deflazacort is 6-36 mg per day, having a target dose of 18 or 24 mg per day; or, the subject weight range is greater than 30 kg and less than or equal to 50 kg and the fixed target dose range of deflazacort is 24-66 mg per day, having a target dose of 36 mg per day; or, the subject weight range is greater than 50 kg and the fixed target dose range of deflazacort is 42-96 mg per day, having a target dose of 48, 54 or 60 mg per day. 
     
     
         5 . The method of  claim 4 , wherein the fixed target dose range of deflazacort for a subject weight range less than or equal to 30 kg is selected from 12-36 mg per day, having a target dose of 18 mg per day for an ambulatory subject or, 18-54 mg per day, having a target dose of 24 mg per day for a non-ambulatory subject; or, wherein the fixed target dose range of deflazacort for a subject weight range greater than 30 kg and less than or equal to 50 kg is selected from 24-60 mg per day, having a target dose of 36 mg per day for an ambulatory subject or 30-72 mg per day, having a target dose of 42 mg per day for a non-ambulatory subject; or, wherein the fixed target dose range of deflazacort for a subject weight range greater than 50 kg is selected from 48-72 mg per day, having a target dose of 48 mg per day for an ambulatory subject or, 54-96 mg per day, having a target dose of 54 mg per day for a non-ambulatory subject. 
     
     
         6 . The method of  claim 1 , wherein the target dose selected from a fixed target dose range of deflazacort for a subject less than or equal to 11 years of age and having a subject weight range less than or equal to 30 kg is selected from 18 mg per day for an ambulatory subject or, 24 mg per day for a non-ambulatory subject; or, wherein the target dose selected from a fixed target dose range of deflazacort for a subject greater than 11 years of age and less than or equal to 18 years of age and having a subject weight range greater than 30 kg and less than or equal to 50 kg is selected from 36 mg per day for an ambulatory subject or, 42 mg per day for a non-ambulatory subject; or, wherein the target dose selected from a fixed target dose range of deflazacort for a subject greater than 18 years of age and having a subject weight range greater than 50 kg is selected from 48 mg per day for an ambulatory subject or, 54 mg per day for a non-ambulatory subject. 
     
     
         7 . The method of  claim 1 , wherein the dosing schedule comprises, a scheduled period selected from administering the fixed dose daily; or, administering twice the daily fixed dose on alternate days; or, administering thrice the daily fixed dose on each of 10 days followed by 10 days with no fixed dose administration; or, administering thrice to five times the daily fixed dose on each of 2 days followed by 5 days with no fixed dose administration. 
     
     
         8 . The method of  claim 1 , wherein the dosing schedule comprises, administering the fixed dose for a plurality of scheduled periods, wherein the fixed dose is been reduced by 6 mg for each period until deflazacort is no longer administered. 
     
     
         9 . The method of  claim 1 , wherein the factors further comprise concomitant administration of a CYP 3A4 inducer, concomitant administration of a CYP 3A4 inhibitor or concomitant administration of a P-glycoprotein (Pgp) inhibitor. 
     
     
         10 . The method of  claim 9 , wherein the CYP3A4 inducer is a moderate or strong CYP3A4 inducer. 
     
     
         11 . The method of  claim 10 , wherein the CYP3A4 inducer is a moderate CYP3A4 inducer and the dosage of deflazacort is increased about Two-Fold to about Three-Fold. 
     
     
         12 . The method of  claim 10 , wherein the CYP3A4 inducer is a strong CYP3A4 inducer and the dosage of deflazacort is increased about Four-Fold to about Six-Fold. 
     
     
         13 . The method of  claim 9 , wherein the CYP3A4 inhibitor is a moderate or strong CYP3A4 inhibitor. 
     
     
         14 . The method of  claim 13 , wherein the CYP3A4 inhibitor is a moderate CYP3A4 inhibitor and the dosage of deflazacort is reduced about Two-Fold to about Three-Fold. 
     
     
         15 . The method of  claim 13 , wherein the CYP3A4 inhibitor is a strong CYP3A4 inhibitor and the dosage of deflazacort is reduced about Three-Fold to about Four-Fold. 
     
     
         16 . The method of  claim 9 , wherein the fixed dose of deflazacort is reduced about Three-Fold to about Four-Fold during concomitant administration of a Pgp inhibitor. 
     
     
         17 . A pharmaceutical composition for use in providing a fixed dose deflazacort therapy to a subject that is suffering from Duchenne muscular dystrophy (DMD) comprising, oral administration of the composition formulated as an oral dosage form selected from a tablet or an oral suspension. 
     
     
         18 . The pharmaceutical composition of  claim 17 , wherein the tablet contains an amount of deflazacort selected from 6 mg, 18 mg, 30 mg or 36 mg in admixture with excipients selected from colloidal silicon dioxide, lactose monohydrate, magnesium stearate, and pre-gelatinized corn starch. 
     
     
         19 . The pharmaceutical composition of  claim 17 , wherein the oral suspension contains 22.75 mg/mL of deflazacort in a suspension with acetic acid, aluminum magnesium silicate, benzyl alcohol, carboxymethylcellulose sodium, polysorbate 80, purified water, and sorbitol. 
     
     
         20 . The pharmaceutical composition of  claim 17 , wherein the deflazacort oral suspension contains 13 mL of the suspension in a 20 mL bottle.