Method of weight management

Abstract

Provided are methods of determining if an individual is a responder to treatment with (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof. Also provided are methods for selecting an individual for treatment with (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof from a plurality of individuals in need of weight management. Also provided are methods for weight management in an individual in need thereof. Also provided are compounds, compositions, and kits for use in a method of weight management in an individual.

1 . A method of determining if an individual is a responder to treatment with (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof, comprising the steps of:
 measuring an individual's responsiveness to (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof after a first time period of administration of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof to the individual,   wherein if the individual has achieved a threshold effect after said first time period of administration, the individual is a responder.   
     
     
         2 . A method for selecting an individual for treatment with (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof from a plurality of individuals in need of weight management, comprising:
 measuring an individual's responsiveness to (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof after a first time period of administration of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof to the individual; and   selecting the individual for treatment with (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof if the individual has achieved a threshold effect after said first time period of administration.   
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein said first time period of administration is from about 4 weeks to about 4 months. 
     
     
         5 . The method of  claim 4 , wherein said first time period of administration is about 12 weeks. 
     
     
         6 . The method of  claim 1 , wherein said threshold effect comprises a decrease in an assessment of weight. 
     
     
         7 .- 20 . (canceled) 
     
     
         21 . The method of  claim 6 , wherein a decrease in an assessment of weight comprises weight loss of at least about 5%. 
     
     
         22 . The method of  claim 6 , wherein a decrease in an assessment of weight comprises weight loss of at least about 5% and said first time period of administration is about 12 weeks. 
     
     
         23 .- 31 . (canceled) 
     
     
         32 . The method of  claim 1 , wherein achievement of a threshold effect after the first time period of administration correlates with a likelihood of the individual achieving one or more additional beneficial effects after a second time period of administration. 
     
     
         33 .- 38 . (canceled) 
     
     
         39 . A method for weight management in an individual in need thereof, comprising the steps of:
 administering a therapeutically effective amount of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof to an individual,   wherein said individual has previously been determined to be a responder according to  claim 1 .   
     
     
         40 . A method for weight management in an individual in need thereof, comprising the steps of:
 administering to the individual a therapeutically effective amount of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof;   determining whether the individual is a responder according to  claim 1 ; and   continuing administration of the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof if the individual is identified as a responder, or   modifying the administration of the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof to the individual if the individual is not identified as a responder.   
     
     
         41 . The method of  claim 39 , wherein weight management comprises weight loss. 
     
     
         42 . The method of  claim 39 , wherein weight management comprises controlling weight gain. 
     
     
         43 . The method of  claim 39 , wherein weight management comprises maintenance of weight loss. 
     
     
         44 . A method for decreasing food intake in an individual in need thereof, comprising the steps of:
 administering a therapeutically effective amount of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof to an individual,   wherein said individual has previously been determined to be a responder according to  claim 1 .   
     
     
         45 . A method for decreasing food intake in an individual in need thereof, comprising the steps of:
 administering to the individual a therapeutically effective amount of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof;   determining whether the individual is a responder according to the method of  claim 1 ; and   continuing administration of the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof if the individual is identified as a responder, or   modifying the administration of the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof to the individual if the individual is not identified as a responder.   
     
     
         46 . A method for inducing satiety in an individual in need thereof, comprising the steps of:
 administering a therapeutically effective amount of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof to an individual,   wherein said individual has previously been determined to be a responder according to  claim 1 .   
     
     
         47 . A method for inducing satiety in an individual in need thereof, comprising the steps of:
 administering to the individual a therapeutically effective amount of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof;   determining whether the individual is a responder according to the method of  claim 1 ; and   continuing administration of the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof if the individual is identified as a responder, or   modifying the administration of the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof to the individual if the individual is not identified as a responder.   
     
     
         48 . A method for the treatment of obesity in an individual in need thereof, comprising the steps of:
 administering a therapeutically effective amount of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof to an individual,   wherein said individual has previously been determined to be a responder according to  claim 1 .   
     
     
         49 . A method for the treatment of obesity in an individual in need thereof, comprising the steps of:
 administering to the individual a therapeutically effective amount of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof;   determining whether the individual is a responder according to the method of  claim 1 ; and   continuing administration of the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof if the individual is identified as a responder, or   modifying the administration of the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof to the individual if the individual is not identified as a responder.   
     
     
         50 . A method for the prevention of obesity in an individual in need thereof, comprising the steps of:
 administering a therapeutically effective amount of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof to an individual,   wherein said individual has previously been determined to a responder according to  claim 1 .   
     
     
         51 . A method for the prevention of obesity in an individual in need thereof, comprising the steps of:
 administering to the individual a therapeutically effective amount of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof;   determining whether the individual is a responder according to the method of  claim 1 ; and   continuing administration of the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof if the individual is identified as a responder, or   modifying the administration of the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof to the individual if the individual is not identified as a responder.   
     
     
         52 .- 64 . (canceled) 
     
     
         65 . The method of  claim 40 , wherein modifying the administration of the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof comprises increasing the dose and/or frequency of administration of the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof. 
     
     
         66 . (canceled) 
     
     
         67 . The method of  claim 40 , wherein modifying the administration of the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof comprises discontinuing the prescribing or administering of the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof. 
     
     
         68 . (canceled) 
     
     
         69 . The method of  claim 40  any one of  claims 40 - 43 ,  45 ,  47 ,  49 , or  51 , wherein modifying the administration of the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof comprises prescribing or administering a weight loss compound or procedure to the individual to be used in combination with the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof. 
     
     
         70 . (canceled) 
     
     
         71 . The method of  claim 40 , wherein modifying the administration of the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof comprises prescribing or administering to the individual a weight loss compound chosen from cannabinoid CB1 receptor antagonists, lipase inhibitors, monoamine reuptake inhibitors, anticonvulsants, glucose sensitizers, incretin mimetics, amylin analogs, GLP-1 analogs, Y receptor peptides, 5HT2C serotonin receptor agonists, opioid receptor antagonists, appetite suppressants, anorectics, and hormones. 
     
     
         72 . (canceled) 
     
     
         73 . The method of  claim 40 , wherein modifying the administration of the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof comprises prescribing or administering to the individual a weight loss compound chosen from amphetamine, caffeine, bromocriptine, ephedrine, pseudoephedrine, phenylpropanolamine, diethylpropion, benzphetamine, rimonabant, mazindol, surinabant, orlistat, cetilistat, sibutramine, bupropion, citalopram, escitalopram, fluoxetine, paroxetine, sertraline, duloxetine, milnacipran, mirtazapine, venlafaxine, desvenlafaxine, topiramate, zonisamide, metformin, exenatide, pramlintide, liraglutide, obinepitide, naltrexone, phentermine, phendimetrazine, insulin, dexfenfluramine, fenfluramine, leptin, naltrexone, and pharmaceutically acceptable salts and combinations thereof. 
     
     
         74 . (canceled) 
     
     
         75 . The method of  claim 69 , wherein the weight loss compound is phentermine. 
     
     
         76 . (canceled) 
     
     
         77 . The method of  claim 69 , wherein the procedure comprises a surgical weight loss procedure. 
     
     
         78 . (canceled) 
     
     
         79 . The method of  claim 1 , wherein the method further comprises prescribing and/or administering a reduced-calorie diet. 
     
     
         80 . The method of  claim 1 , wherein the method further comprises prescribing and/or administering a program of regular exercise. 
     
     
         81 . The method of  claim 1 , wherein the individual has an initial body mass index ≧25 kg/m 2 . 
     
     
         82 . The method of  claim 1 , wherein the individual has an initial body mass index ≧27 kg/m 2 . 
     
     
         83 . The method of  claim 81 , wherein the individual has at least one weight related comorbid condition. 
     
     
         84 . The method of  claim 83 , wherein the weight related comorbid condition is selected from: hypertension, dyslipidemia, cardiovascular disease, glucose intolerance and sleep apnea. 
     
     
         85 . The method of  claim 84 , wherein the weight related comorbid condition is selected from: hypertension, dyslipidemia, and type 2 diabetes. 
     
     
         86 . The method of  claim 1 , wherein the individual has an initial body mass index ≧30 kg/m 2 . 
     
     
         87 . (canceled) 
     
     
         88 . (canceled) 
     
     
         89 . The method of  claim 1 , wherein the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof is (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride or a solvate or hydrate thereof. 
     
     
         90 . The method of  claim 89 , wherein the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof is (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride hemihydrate. 
     
     
         91 . The method of  claim 90 , wherein the (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride or a solvate or hydrate thereof is prescribed and/or administered to the individual in a dose equal to or less than 20 mg per day. 
     
     
         92 . The method of  claim 91 , wherein the is (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride or a solvate or hydrate thereof is prescribed and/or administered to the individual in a dose equal to or less than 10 mg twice per day. 
     
     
         93 . (canceled)