Co-therapy comprising canagliflozin and phentermine for the treatment of obesity and obesity related disorders

Abstract

The present invention is directed to the use of co-therapy comprising administration of canagliflozin and phentermine for the treatment of obesity and obesity related disorders. More particularly, the present invention is directed to co-therapy for treating obesity, for promoting weight loss and/or for suppressing appetite; for treating, delaying, slowing the progression of and/or preventing metabolic disorders (including for example Type 2 diabetes mellitus); for treating, delaying, slowing the progression of and/or preventing renal or fatty liver disorders (including for example NASH, NAFLD, etc.); for treating, delaying, slowing the progression of and/or preventing sleep disorders (including for example sleep apnea); for providing cardiovascular protection; for treating, delaying, slowing the progression of and/or preventing cardiovascular events (including major adverse cardiac events (MACE) such as myocardial infarction, unstable angina, cardiovascular death, revascularization, fatal or non-fatal cerebrovascular accident, peripheral arteriopathy, aortic events, hospitalization due to congestive heart failure, etc.); and/or for extending or prolonging life span.

1 . A method for treating, delaying, slowing the progression of or preventing obesity or an obesity related disorder comprising administering to a subject in need thereof a therapeutically effective amount of co-therapy comprising
 (a) canagliflozin; wherein the canagliflozin is administered in an amount in the range of from about 50 mg to about 500 mg per day; and   (b) phentermine; wherein the phentermine is administered in an amount in the range of from about 3.75 mg to about 50 mg per day.   
     
     
         2 . A method for treating obesity, promoting weight loss, suppressing appetite, decreasing food intake, inducing satiety or controlling weight gain comprising administering to a subject in need thereof a therapeutically effective amount of co-therapy consisting essentially of
 (a) canagliflozin; wherein the canagliflozin is administered in an amount in the range of from about 50 mg to about 500 mg per day; and   (b) phentermine; wherein the phentermine is administered in an amount in the range of from about 3.75 mg to about 50 mg per day.   
     
     
         3 - 9 . (canceled) 
     
     
         10 . A method as in any of  claim 1  wherein the subject in need thereof is overweight or obese. 
     
     
         11 . A method as in any of  claim 1  further comprising identifying the subject in need thereof by determining the subject's body mass index (BMI). 
     
     
         12 . A method as in any of  claim 1  wherein the subject in need thereof is a subject whose body mass index is greater than or equal to about 25 kg/m 2 . 
     
     
         13 . A method as in any of  claim 1 , wherein the subject achieves a weight loss after 26 Weeks of between about 5% and about 10%. 
     
     
         14 . A method as in any of  claim 1 , wherein the subject in need thereof is a subject who (a) has measured body mass index is greater than or equal to about 25 kg/m 2 ; (b) is a candidate for or has had bariatric surgery; or (c) is a candidate for or has had implanted a weight loss promoting device. 
     
     
         15 . A method as in  claim 2 , wherein the subject in need thereof is overweight or obese; and wherein the subject in need thereof has been diagnosed with or exhibits one or more symptoms of a disorder selected from the group consisting of pre-diabetes, impaired oral glucose tolerance, Type II diabetes mellitus, Metabolic Syndrome, cardiovascular risk, renal or fatty liver disorder and sleep apnea. 
     
     
         16 . A method as in  claim 2 , wherein the subject in need thereof has been diagnosed with or shows one or more symptoms of one or more of the following conditions: (a) diabetes mellitus, regardless of type; (b) chronic kidney disease (CKD); (c) acute renal failure (ARF); (d) renal transplant recipients; (e) renal transplant donors; (f) unilateral total or partial nephrectomized patients; or (g) nephrotic syndrome. 
     
     
         17 . A method as in  claim 2 , wherein the subject in need thereof is
 (1) an individual diagnosed with one or more of the conditions selected from the group consisting of overweight, obesity, visceral obesity and abdominal obesity; or   (2) an individual who shows one, two or more of the following signs:
 (a) a fasting blood glucose or serum glucose concentration greater than about 100 mg/dL, in particular greater than about 125 mg/dL; 
 (b) a postprandial plasma glucose equal to or greater than about 140 mg/dL; 
 (c) an HbA1c value equal to or greater than about 7.0%; or 
   (3) an individual wherein one, two, three or more of the following conditions are present:
 (a) obesity, visceral obesity and/or abdominal obesity, 
 (b) triglyceride blood level equal to or greater than about 150 mg/dL, 
 (c) HDL-cholesterol blood level less than about 40 mg/dL in female patients and less than about 50 mg/dL in male patients, 
 (d) a systolic blood pressure equal to or greater than about 130 mm Hg and a diastolic blood pressure equal to or greater than about 85 mm Hg, 
 (e) a fasting blood glucose level equal to or greater than about 100 mg/dL. 
   
     
     
         18 . A method as in  claim 2 , wherein the subject in need thereof is diabetic or pre-diabetic. 
     
     
         19 . A method as in  claim 2 , wherein the subject in need thereof is non-diabetic. 
     
     
         20 . (canceled) 
     
     
         21 . A method as in  claim 1 , wherein the obesity related disorder is selected from the group consisting of a metabolic disorder, a renal or fatty liver disorder, a cardiovascular event, and sleep apnea. 
     
     
         22 - 33 . (canceled) 
     
     
         34 . A method as in any of  claim 1 , wherein the canagliflozin is administered as a crystalline hemihydrate. 
     
     
         35 . A method as in any of  claim 1 , wherein the canagliflozin is administered in an amount in the range of from about 100 to about 300 mg. 
     
     
         36 . A method as in any of  claim 1 , wherein the canagliflozin is administered in an amount of about 100 mg or about 300 mg. 
     
     
         37 . A method as in any of  claim 1 , wherein the phentermine is phentermine hydrochloride. 
     
     
         38 . A method as in any of  claim 1 , wherein the phentermine is administered in an amount in the range of from about 3.75 mg to about 37.5 mg. 
     
     
         39 . A method as in any of  claim 1 , wherein the phentermine is administered in an amount of about 3.75 mg, about 7.5 mg, about 15 mg, about 30 mg or about 37.5 mg. 
     
     
         40 . A method as in any of  claim 1 , wherein the phentermine is administered in an amount of about 3.75 mg, about 7.5 mg or about 15 mg. 
     
     
         41 - 44 . (canceled) 
     
     
         45 . A pharmaceutical composition comprising
 (a) canagliflozin; wherein the canagliflozin is administered in an amount in the range of from about 50 mg to about 500 mg per day;   (b) phentermine; wherein the phentermine is administered in an amount in the range of from about 3.75 mg to about 50 mg per day; and   (c) a pharmaceutically acceptable carrier or excipient.   
     
     
         46 - 49 . (canceled) 
     
     
         50 . A method for chronic weight management comprising administering to a subject in need thereof a therapeutically effective amount of co-therapy comprising (a) canagliflozin and (b) phentermine; 
       wherein the subject in need thereof is a subject with an initial body mass index greater than or equal to about 30 kg/m 2 ; or greater than or equal to about 27 kg/m 2  and diagnosed with or exhibiting at least one weight-related co-morbid condition. 
     
     
         51 . The method of  claim 50 , wherein the co-therapy is an adjunct to a reduced-calorie diet and increased physical activity.