Methods for the treatment of diseases ameliorated by PDE4 inhibition using dosage titration of apremilast
AssigneeCelgene Corporation
InventorRobert Day
Life of this patent
Estimating the term…
Abstract
Methods of treating, managing or preventing diseases ameliorated by inhibiting PDE4 such as psoriasis, ankylosing spondylitis, Behcet's disease, rheumatoid arthritis, atopic dermatitis, Crohn's disease, and ulcerative colitis are disclosed. Specific methods encompass the administration of apremilast in specific dosage titration schedule, alone or in combination with a second active agent.
Claims24
A method for treating a patient with stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, wherein the patient is suffering from psoriasis, the method consisting of:
- (a) administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione in an initial titration dosing schedule consisting of
- (i) 10 mg in the morning on the first day of administration;
- (ii) 10 mg in the morning and 10 mg after noon on the second day of administration;
- (iii) 10 mg in the morning and 20 mg after noon on the third day of administration;
- (iv) 20 mg in the morning and 20 mg after noon on the fourth day of administration;
- (v) 20 mg in the morning and 30 mg after noon on the fifth day of administration;
- and
- (b) on the sixth and every subsequent day, administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione at a dose of between about 40 mg/day and about 100 mg/day.
A method for treating a patient with stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, wherein the patient is suffering from psoriasis, the method consisting of:
- (a) administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione in an initial titration dosing schedule consisting of
- (i) 10 mg in the morning on the first day of administration;
- (ii) 10 mg in the morning and 10 mg after noon on the second day of administration;
- (iii) 10 mg in the morning and 20 mg after noon on the third day of administration;
- (iv) 20 mg in the morning and 20 mg after noon on the fourth day of administration;
- (v) 20 mg in the morning and 30 mg after noon on the fifth day of administration;
- and
- (b) on the sixth and every subsequent day, administering to the patient 30 mg in the morning and 30 mg after noon of stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione.
A method for treating a patient with stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, wherein the patient is suffering from ankylosing spondylitis, the method consisting of:
- (a) administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione in an initial titration dosing schedule consisting of
- (i) 10 mg in the morning on the first day of administration;
- (ii) 10 mg in the morning and 10 mg after noon on the second day of administration;
- (iii) 10 mg in the morning and 20 mg after noon on the third day of administration;
- (iv) 20 mg in the morning and 20 mg after noon on the fourth day of administration;
- (v) 20 mg in the morning and 30 mg after noon on the fifth day of administration;
- and
- (b) on the sixth and every subsequent day, administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione at a dose of between about 40 mg/day and about 100 mg/day.
A method for treating a patient with stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, wherein the patient is suffering from ankylosing spondylitis, the method consisting of:
- (a) administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione in an initial titration dosing schedule consisting of
- (i) 10 mg in the morning on the first day of administration;
- (ii) 10 mg in the morning and 10 mg after noon on the second day of administration;
- (iii) 10 mg in the morning and 20 mg after noon on the third day of administration;
- (iv) 20 mg in the morning and 20 mg after noon on the fourth day of administration;
- (v) 20 mg in the morning and 30 mg after noon on the fifth day of administration;
- and
- (b) on the sixth and every subsequent day, administering to the patient 30 mg in the morning and 30 mg after noon of stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione.
A method for treating a patient with stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, wherein the patient is suffering from Behcet's disease, the method consisting of:
- (a) administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione in an initial titration dosing schedule consisting of
- (i) 10 mg in the morning on the first day of administration;
- (ii) 10 mg in the morning and 10 mg after noon on the second day of administration;
- (iii) 10 mg in the morning and 20 mg after noon on the third day of administration;
- (iv) 20 mg in the morning and 20 mg after noon on the fourth day of administration;
- (v) 20 mg in the morning and 30 mg after noon on the fifth day of administration;
- and
- (b) on the sixth and every subsequent day, administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione at a dose of between about 40 mg/day and about 100 mg/day.
A method for treating a patient with stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, wherein the patient is suffering from Behcet's disease, the method consisting of:
- (a) administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione in an initial titration dosing schedule consisting of
- (i) 10 mg in the morning on the first day of administration;
- (ii) 10 mg in the morning and 10 mg after noon on the second day of administration;
- (iii) 10 mg in the morning and 20 mg after noon on the third day of administration;
- (iv) 20 mg in the morning and 20 mg after noon on the fourth day of administration;
- (v) 20 mg in the morning and 30 mg after noon on the fifth day of administration;
- and
- (b) on the sixth and every subsequent day, administering to the patient 30 mg in the morning and 30 mg after noon of stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione.
A method for treating a patient with stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, wherein the patient is suffering from rheumatoid arthritis, the method consisting of:
- (a) administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione in an initial titration dosing schedule consisting of
- (i) 10 mg in the morning on the first day of administration;
- (ii) 10 mg in the morning and 10 mg after noon on the second day of administration;
- (iii) 10 mg in the morning and 20 mg after noon on the third day of administration;
- (iv) 20 mg in the morning and 20 mg after noon on the fourth day of administration;
- (v) 20 mg in the morning and 30 mg after noon on the fifth day of administration;
- and
- (b) on the sixth and every subsequent day, administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione at a dose of between about 40 mg/day and about 100 mg/day.
A method for treating a patient with stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, wherein the patient is suffering from rheumatoid arthritis, the method consisting of:
- (a) administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione in an initial titration dosing schedule consisting of
- (i) 10 mg in the morning on the first day of administration;
- (ii) 10 mg in the morning and 10 mg after noon on the second day of administration;
- (iii) 10 mg in the morning and 20 mg after noon on the third day of administration;
- (iv) 20 mg in the morning and 20 mg after noon on the fourth day of administration;
- (v) 20 mg in the morning and 30 mg after noon on the fifth day of administration;
- and
- (b) on the sixth and every subsequent day, administering to the patient 30 mg in the morning and 30 mg after noon of stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione.
A method for treating a patient with stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, wherein the patient is suffering from atopic dermatitis, the method consisting of:
- (a) administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione in an initial titration dosing schedule consisting of
- (i) 10 mg in the morning on the first day of administration;
- (ii) 10 mg in the morning and 10 mg after noon on the second day of administration;
- (iii) 10 mg in the morning and 20 mg after noon on the third day of administration;
- (iv) 20 mg in the morning and 20 mg after noon on the fourth day of administration;
- (v) 20 mg in the morning and 30 mg after noon on the fifth day of administration;
- and
- (b) on the sixth and every subsequent day, administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione at a dose of between about 40 mg/day and about 100 mg/day.
A method for treating a patient with stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, wherein the patient is suffering from atopic dermatitis, the method consisting of:
- (a) administering to the patient of stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione in an initial titration dosing schedule consisting of
- (i) 10 mg in the morning on the first day of administration;
- (ii) 10 mg in the morning and 10 mg after noon on the second day of administration;
- (iii) 10 mg in the morning and 20 mg after noon on the third day of administration;
- (iv) 20 mg in the morning and 20 mg after noon on the fourth day of administration;
- (v) 20 mg in the morning and 30 mg after noon on the fifth day of administration;
- and
- (b) on the sixth and every subsequent day, administering to the patient 30 mg in the morning and 30 mg after noon of stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione.
A method for treating a patient with stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, wherein the patient is suffering from Crohn's disease, the method consisting of:
- (a) administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione in an initial titration dosing schedule consisting of
- (i) 10 mg in the morning on the first day of administration;
- (ii) 10 mg in the morning and 10 mg after noon on the second day of administration;
- (iii) 10 mg in the morning and 20 mg after noon on the third day of administration;
- (iv) 20 mg in the morning and 20 mg after noon on the fourth day of administration;
- (v) 20 mg in the morning and 30 mg after noon on the fifth day of administration;
- and
- (b) on the sixth and every subsequent day, administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione at a dose of between about 40 mg/day and about 100 mg/day.
A method for treating a patient with stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, wherein the patient is suffering from Crohn's disease, the method consisting of:
- (a) administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione in an initial titration dosing schedule consisting of
- (i) 10 mg in the morning on the first day of administration;
- (ii) 10 mg in the morning and 10 mg after noon on the second day of administration;
- (iii) 10 mg in the morning and 20 mg after noon on the third day of administration;
- (iv) 20 mg in the morning and 20 mg after noon on the fourth day of administration;
- (v) 20 mg in the morning and 30 mg after noon on the fifth day of administration;
- and
- (b) on the sixth and every subsequent day, administering to the patient 30 mg in the morning and 30 mg after noon of stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione.
A method for treating a patient with stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, wherein the patient is suffering from ulcerative colitis, the method consisting of:
- (a) administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione in an initial titration dosing schedule consisting of
- (i) 10 mg in the morning on the first day of administration;
- (ii) 10 mg in the morning and 10 mg after noon on the second day of administration;
- (iii) 10 mg in the morning and 20 mg after noon on the third day of administration;
- (iv) 20 mg in the morning and 20 mg after noon on the fourth day of administration;
- (v) 20 mg in the morning and 30 mg after noon on the fifth day of administration;
- and
- (b) on the sixth and every subsequent day, administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione at a dose of between about 40 mg/day and about 100 mg/day.
A method for treating a patient with stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione, wherein the patient is suffering from ulcerative colitis, the method consisting of:
- (a) administering to the patient stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione in an initial titration dosing schedule consisting of
- (i) 10 mg in the morning on the first day of administration;
- (ii) 10 mg in the morning and 10 mg after noon on the second day of administration;
- (iii) 10 mg in the morning and 20 mg after noon on the third day of administration;
- (iv) 20 mg in the morning and 20 mg after noon on the fourth day of administration;
- (v) 20 mg in the morning and 30 mg after noon on the fifth day of administration;
- and
- (b) on the sixth and every subsequent day, administering to the patient 30 mg in the morning and 30 mg after noon of stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione.
Dependencies are inferred from the claim text.