Methods for the treatment of diseases ameliorated by PDE4 inhibition using dosage titration of apremilast

Patent metadata

Field	Value
Publication number	US-10092541-B2
Application number	US-201514826027-A
Country	US
Kind code	B2
Filing date	Aug 13, 2015
Priority date	Aug 15, 2014
Publication date	Oct 9, 2018
Grant date	Oct 9, 2018

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.

First claim

What is claimed is:

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. A method for treating a patient with stereomerically pure (+)-2-[1-(3-ethoxy-4-methoxyphenyl)-2-methylsulfonylethyl]-4-acetylaminoisoindoline-1,3-dione,

Assignees

• Celgene Corp

Inventors

• Day Robert

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P27/02

  Ophthalmic agents · CPC title

• A61K38/13

  Cyclosporins · CPC title

• A61K31/635

  having a heterocyclic ring, e.g. sulfadiazine · CPC title

• A61K31/42

  Oxazoles · CPC title