Oral octreotide administered in combination with other therapeutic agents

Abstract

This invention relates to combination therapy of a subject suffering from acromegaly. The method of treatment comprises administration to the subject of a therapeutically effective amount of oral somatostatin receptor ligand (SRL) e.g. octreotide in combination with a therapeutically effective amount of a dopamine agonist and/or a growth hormone receptor antagonist and/or a selective estrogen receptor modulator (SERM) and/or a 2 nd somatostatin receptor ligand (SRL).

1 . A method of treatment of a subject suffering from acromegaly which comprises administration to the subject of a therapeutically effective amount of an oral somatostatin receptor ligand (SRL) in combination with a therapeutically effective amount of a dopamine agonist or a growth hormone receptor antagonist or a 2nd somatostatin receptor ligand (SRL) or a selective estrogen receptor modulator (SERM). 
     
     
         2 . The method of treatment of  claim 1  wherein the oral somatostatin receptor ligand (SRL) is octreotide or lanreotide or pasireotide. 
     
     
         3 - 5 . (canceled) 
     
     
         6 . The method of  claim 1  wherein the dopamine agonist is cabergoline. 
     
     
         7 . The method of- claim 1  wherein the dopamine agonist is bromocriptine. 
     
     
         8 . The method of- claim 1  wherein the growth hormone receptor antagonist is pegvisomant or ATL1103. 
     
     
         9 - 12 . (canceled) 
     
     
         13 . The method of  claim 6  wherein the administration of cabergoline comprises about 0.2 to about 5 mg of cabergoline weekly. 
     
     
         14 - 16 . (canceled) 
     
     
         17 . The method of  claim 13  wherein the administration of cabergoline is gradually increased from 0.5 mg×2 per week for first two weeks, 1 mg×2 per week for additional two weeks, followed by 1.5 mg×2 per week for additional two weeks reaching a maintenance dose of 1.75 mg×2 per week 
     
     
         18 . The method of  claim 13  wherein the administration of cabergoline is a maintenance dose of 3.0 mg to 3.5 mg weekly. 
     
     
         19 . The method of  claim 8  wherein the administration of pegvisomant comprises about 2 mg to about 60 mg of pegvisomant daily or once, twice, three, four, five or six times per week. 
     
     
         20 - 21 . (canceled) 
     
     
         22 . The method of  claim 1  wherein the SERM is clomiphene. 
     
     
         23 - 27 . (canceled) 
     
     
         28 . The method of  claim 1  wherein the 2nd somatostatin receptor ligand is a long-acting injectable formulation. 
     
     
         29 - 32 . (canceled) 
     
     
         33 . The method of  claim 2  wherein the administration of oral octreotide comprises about 10 to about 80 mg of octreotide daily, such as 10, 20, 30, 40, 50, 60, 70 or 80 mg daily. 
     
     
         34 - 38 . (canceled) 
     
     
         39 . A unit dosage formulation for oral administration comprising an oral SRL and a dopamine agonist. 
     
     
         40 . The unit dosage formulation of  claim 39  wherein the dopamine agonist is cabergoline. 
     
     
         41 . The unit dosage formulation of  claim 39  wherein the oral SRL is octreotide. 
     
     
         42 . (canceled) 
     
     
         43 . A unit dosage formulation for oral administration comprising an oral SRL and SERM. 
     
     
         44 . The unit dosage formulation of  claim 43  wherein the SERM is clomiphene. 
     
     
         45 . The unit dosage formulation of  claim 43  wherein the oral SRL is octreotide. 
     
     
         46 . The unit dosage formulation of  claim 45  which comprises 5-120 mg octreotide and clomiphene. 
     
     
         47 - 67 . (canceled)