Tesofensine and metoprolol for treatment of hypertension

Abstract

The present invention relates to treatment of hypertension using a combination of tesofensine and metoprolol. The treatment is particularly well suited for the treatment of hypertensive obese subjects and hypertensive diabetic subjects.

1 . A method for treating hypertension or pre-hypertension in a hypertensive or pre-hypertensive subject, comprising administering to said subject:
 i) 0.1 mg to 1 mg of tesofensine or a pharmaceutically acceptable salt thereof;   ii) 10 mg to 200 mg of metoprolol or a pharmaceutically acceptable salt thereof.   
     
     
         2 . (canceled) 
     
     
         3 . The method according to  claim 1 , wherein the subject is suffering from pre-hypertension, stage 1 hypertension, stage 2 hypertension or isolated systolic hypertension, prior to the administration. 
     
     
         4 . The method according to  claim 1 , wherein the subject has a systolic blood pressure in the range of 120-139 mmHg and a diastolic blood pressure in the range of 80-89 mmHg, prior to the administration. 
     
     
         5 . The method according to  claim 1 , wherein the subject has a systolic blood pressure above 135 mmHg and/or a diastolic blood pressure above 85 mmHg, prior to the administration. 
     
     
         6 . The method according to  claim 1 , wherein the subject has a systolic blood pressure above 140 mmHg and/or a diastolic blood pressure above 90 mmHg, prior to the administration. 
     
     
         7 . The method according to  claim 1 , wherein the subject has a systolic blood pressure in the range of 140-159 mmHg and a diastolic blood pressure in the range of 90-99 mmHg, prior to the administration. 
     
     
         8 . The method according to  claim 1 , wherein the subject has a systolic blood pressure in the range of 160-179 mmHg and a diastolic blood pressure in the range of 100-109 mmHg, prior to the administration. 
     
     
         9 . The method according to  claim 1 , wherein the subject has a systolic blood pressure at or above 140 mmHg and a diastolic blood pressure below 90 mmHg, prior to the administration. 
     
     
         10 . The method according to  claim 1 , wherein the subject is a child or an adolescent having an average systolic blood pressure (SBP) or diastolic blood pressure (DBP) that is ≥95th percentile for gender, age, and height on at least 3 separate occasions or wherein the subject has an average SBP or DBP levels that are ≥90th percentile but <95th percentile, prior to the administration. 
     
     
         11 . The method according to  claim 1 , wherein the subject is obese, prior to the administration. 
     
     
         12 . The method according to  claim 1 , wherein the subject has a BMI above 25 kg/m 2 . 
     
     
         13 . The method according to  claim 12 , wherein the subject has a BMI above 30 kg/m 2 . 
     
     
         14 . The method according to  claim 1 , wherein the subject is suffering from diabetes, prior to the administration. 
     
     
         15 . The method according to  claim 14 , wherein the diabetes is type 1 diabetes, type 2 diabetes, pre-diabetes, or gestational diabetes. 
     
     
         16 . The method according to  claim 14 , wherein the subject is suffering from type 1 diabetes, prior to the administration. 
     
     
         17 . The method according to  claim 14 , wherein the subject is suffering from type 2 diabetes, prior to the administration. 
     
     
         18 . The method according to  claim 14 , wherein the subject is suffering from pre-diabetes, prior to the administration. 
     
     
         19 . The method according to  claim 14 , wherein the subject is suffering from gestational diabetes, prior to the administration. 
     
     
         20 . The method according to  claim 1 , wherein the subject is further suffering from a disorder or condition that is metabolic syndrome, dyslipidemia, atherosclerosis, drug-induced obesity, an overeating disorder, bulimia nervosa, binge eating disorder, compulsive over-eating, impaired appetite regulation, Prader Willi Syndrome (PWS), nonalcoholic fatty liver disease (NAFLD), or nonalcoholic steatohepatitis (NASH) prior to the administration. 
     
     
         21 . The method according to  claim 1 , wherein the subject is a human. 
     
     
         22 . The method according to  claim 1 , wherein the administration results in a decrease in the systolic blood pressure of the subject and/or a decrease in the diastolic blood pressure of the subject, as compared to prior to the administration. 
     
     
         23 . The method according to  claim 1 , wherein the administration results in a decrease in the systolic blood pressure by at least 5 mm Hg, as compared to the subject's systolic blood pressure prior to the administration. 
     
     
         24 . The method according to  claim 1 , wherein the administration results in a decrease in the systolic blood pressure by at least 5%, as compared to the subject's systolic blood pressure prior to the administration. 
     
     
         25 . The method according to  claim 1 , wherein the administration results in a decrease in the diastolic blood pressure by at least 5 mm Hg, as compared to the subject's diastolic blood pressure prior to the administration. 
     
     
         26 . The method according to  claim 1 , wherein the administration results in a decrease in the diastolic blood pressure by at least 5%, as compared to the subject's diastolic blood pressure prior to the administration. 
     
     
         27 . The method according to  claim 1 , wherein the tesofensine or a pharmaceutically acceptable salt thereof and the metoprolol or a pharmaceutically acceptable salt thereof are administered orally. 
     
     
         28 . The method according to  claim 1 , wherein the tesofensine or a pharmaceutically acceptable salt thereof and the metoprolol or a pharmaceutically acceptable salt thereof are administered simultaneously, sequentially or separately. 
     
     
         29 . The method according  claim 1 , wherein the tesofensine or a pharmaceutically acceptable salt thereof and the metoprolol or a pharmaceutically acceptable salt thereof are co-administered as a single pharmaceutical composition. 
     
     
         30 . The method according to  claim 1 , wherein the metoprolol or a pharmaceutically acceptable salt thereof are administered as a pharmaceutical composition having an extended release profile. 
     
     
         31 . The method according to  claim 1 , wherein the tesofensine or a pharmaceutically acceptable salt thereof is administered to said subject at a dose of 0.25 mg to 0.75 mg of tesofensine per day. 
     
     
         32 . The method according to  claim 1 , wherein the metoprolol or a pharmaceutically acceptable salt thereof is administered to said subject at a dose of 25-100 mg of metoprolol per day. 
     
     
         33 . (canceled) 
     
     
         34 . (canceled) 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . (canceled) 
     
     
         38 . (canceled) 
     
     
         39 . (canceled) 
     
     
         40 . (canceled) 
     
     
         41 . (canceled) 
     
     
         42 . (canceled) 
     
     
         43 . (canceled) 
     
     
         44 . The method according to  claim 1 , wherein the administration results in reduction of the subject's BMI, as compared to prior to the administration. 
     
     
         45 . The method according to  claim 14 , wherein the administration results in alleviation of the diabetes. 
     
     
         46 . The method according to  claim 14 , wherein the administration results in alleviation of diabetic complications in the subject. 
     
     
         47 . The method according to  claim 20 , wherein the subject is suffering from a fatty liver disorder and wherein the administration results in reduction of the fatty liver disorder, as compared to prior to the administration.