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 2nd 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 oral octreotide in combination with a therapeutically effective amount of a dopamine agonist and/or a growth hormone receptor antagonist and/or an injectable somatostatin receptor ligand (SRL) and/or a selective estrogen receptor modulator (SERM). 
     
     
         2 - 3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the level of IGF-1 in the subject is only partially controlled on oral octreotide alone. 
     
     
         5 - 6 . (canceled) 
     
     
         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 . The method of  claim 1 , wherein the administration of octreotide comprises about 5 mg to about 120 mg of octreotide daily. 
     
     
         10 . The method of  claim 9 , wherein the administration of octreotide comprises about 40 to about 80 mg of octreotide daily. 
     
     
         11 - 18 . (canceled) 
     
     
         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 . The method of  claim 8 , wherein the administration of pegvisomant comprises about 10 to about 20 mg of pegvisomant daily or once, twice, three, four, five or six times per week. 
     
     
         21 . The method of  claim 8 , wherein the administration of pegvisomant comprises about 2 to about 10 mg of pegvisomant daily or once, twice, three, four, five or six times per week, such as 2, 4, 6, 8 or 10 mg of pegvisomant daily or once, twice, three, four, five or six times per week. 
     
     
         22 . The method of  claim 1 , wherein the SERM is clomiphene. 
     
     
         23 - 27 . (canceled) 
     
     
         28 . The method of  claim 1 , wherein the injectable somatostatin receptor ligand is a long-acting injectable formulation. 
     
     
         29 - 30 . (canceled) 
     
     
         31 . The method of  claim 28 , wherein the injectable somatostatin receptor ligand is a long-acting injectable formulation which is administered every four weeks. 
     
     
         32 - 33 . (canceled) 
     
     
         34 . The method of  claim 31 , wherein the oral octreotide is administered on an “as needed” basis. 
     
     
         35 . The method of  claim 31 , wherein the oral octreotide is administered on a regular basis. 
     
     
         36 . The method of  claim 31 , wherein the oral octreotide is administered on a daily basis. 
     
     
         37 . The method of  claim 36 , wherein the oral octreotide is administered on a daily basis toward the end of the dosing interval wherein the long-acting somatostatin receptor ligand was administered. 
     
     
         38 . The method of  claim 36 , wherein the oral octreotide is administered on a daily basis during the fourth week after the long-acting somatostatin receptor ligand was administered. 
     
     
         39 - 62 . (canceled) 
     
     
         63 . A method of treatment of a subject suffering from acromegaly comprising the following steps: administering to the subject oral octreotide with an initial dose of 20 mg BID;
 receiving information regarding blood levels of IGF-1 and/or clinical symptoms, and in response to blood levels of IGF-1 and/or clinical symptoms, evaluating the course of treatment,   wherein if blood levels of IGF-1 are normal and/or clinical symptoms are controlled and/or response level (biochemical and symptomatic response) is maintained, maintaining oral octreotide dosage at 20 mg BID;   wherein if IGF-1 levels are increased, or in case of symptomatic exacerbation, dosage of oral octreotide may be adjusted to 60 mg daily (40 mg morning+20 mg evening); continuing to receive information regarding blood levels of IGF-1 and/or clinical symptoms, and evaluating the course of treatment;   wherein if the blood levels of IGF-1 and/or clinical symptoms indicate the subject has failed to respond to dosage of oral octreotide at 80 mg daily for at least two weeks treatment, or subject has inadequate biochemical control on dosage of oral octreotide at 80 mg daily for at least two weeks treatment, co-administering oral octreotide at 80 mg daily with a second therapeutic agent.   
     
     
         64 - 66 . (canceled) 
     
     
         67 . The method of  claim 63 , wherein the combination of oral octreotide and the second therapeutic agent is maintained.