Methods of Administering Monomethyl Fumarate and Prodrugs Thereof Having Reduced Side Effects

A method of systemically administering a therapeutically effective amount of a compound selected from (i) monomethyl fumarate (MMF), (ii) a prodrug of monomethyl fumarate, and (iii) a combination thereof, to treat a disease in a patient in need of such treatment, comprising one of a) or b):

• a) orally administering to the patient, at a dosing frequency of not more than twice per day, an enteric-coated oral sustained release dosage form containing a therapeutically effective dose of the compound(s), wherein the dosage form, when subjected to an in vitro dissolution test employing as a dissolution medium 750 mL of 0.1 N hydrochloric acid, at pH 1.2, for a period of 2 hours, followed by addition of 250 mL of 200 mM tribasic sodium phosphate buffer resulting in an adjustment of the pH of the dissolution medium to 6.8, the dissolution medium being maintained at 37° C. and stirred at 100 rpm,
• releases:
• (i) less than 10 wt % of the dose over an initial 2 hours of the in vitro dissolution test;
• (ii) at least 90 wt % of the dose over not less than an initial 8 hours of the in vitro dissolution test;
• (iii) no more than 30 wt % of the dose in any one hour during the in vitro dissolution test;
• and (iv) no more than 40 wt % of the dose in any consecutive two hours during the in vitro dissolution test;
• or
• b) orally administering to the patient, at a frequency of not more than twice per day, a non-enteric-coated oral sustained release dosage form containing a therapeutically effective dose of the compound(s), wherein the dosage form, when subjected to an in vitro dissolution test employing as a dissolution medium 750 mL of 0.1 N hydrochloric acid, at pH 1.2, for a period of 2 hours, followed by addition of 250 mL of 200 mM tribasic sodium phosphate buffer resulting in an adjustment of the pH of the dissolution medium to 6.8,
• releases (i) at least 90 wt % of the dose over not less than an initial 8 hours of the in vitro dissolution test;
• (ii) no more than 30 wt % of the dose in any one hour during the in vitro dissolution test;
• and (iii) no more than 40 wt % of the dose in any consecutive two hours during the in vitro dissolution test.