effect of tesofensine on energy balance in humans.

Conditions: Obesity

Summary: purpose: to evaluate the effect of tesofensine on energy balance


Eligibility criteria:
inclusion criteria: * overweight to obese subjects with bmi 28 - 35 kg/m² otherwise healthy * males 18 to 50 years of age, extremes included * subjects should be able to comply with study procedures * subjects giving written informed consent exclusion criteria: * use of any concomitant medication including high dose vitamins and regular otc preparations * subjects who have been smokers within the last year * subjects with specific diseases interfering with their metabolism e.g. myxoedema, cushing's syndrome, type 1 diabetes mellitus, significant neurological or psychiatric illness such as epilepsy, schizophrenia, depression, eating disorders such as bulimia. * subjects with type 2 diabetes mellitus are ineligible unless anti-diabetic medication was not deemed necessary by the investigator and fasting (venous or arterialized capillary full blood from finger or ear) blood glucose \> 6.1 mmol/l at screening. re-test is allowed if first measure is above inclusion value. the corresponding exclusion criteria for plasma glucose is 7.0 mmol/l * known hypercholesterolaemia (\> 7 mmol/l). * known hypertriglyceridaemia (\> 3 mmol/l). * malabsorptive intestinal disorders that can be assumed to affect the absorption of tesofensine * mental or psychiatric disorder based on medical history only * subjects with systemic infections or inflammatory diseases * subjects currently (within the past 2 months) known to abuse or to be dependent on any drug, including alcohol (weekly consumption \> 21 units of alcohol ) * hepatic or renal dysfunction (asat and/or alat \> 2 x uln and creatinine clearance \< 30 ml/min estimated by central laboratory using cockcroft and gault formula, respectively) * special diets (e.g., vegetarian, atkins) * subject should not be athletics or planning major changes in physical activity during the study to an extent that may interfere with the study outcome, as judged by the investigator * weight change of \> 3 kg within 2 months prior to screening * surgically treated obesity * history or presence of significant cardiovascular disease such as heart failure, ischemic heart disease, stroke, transient ischemic attacks * significant abnormalities on the ecg according to the investigators opinion. additional exclusionary ecg values: qtcb \> 450 milliseconds(ms), pr interval \> 240 ms, qrs interval \> 120 ms * hypotension (i.e. supine systolic bp \< 90 mm hg) and/or symptomatic orthostatic hypotension (clinical symptoms of orthostatic hypotension associated with a decline ≥ 20 mm hg in systolic bp at one minute after standing compared with the previous supine systolic bp obtained after 5 minutes of quiet rest) at screening visit * hypertension (i.e. sitting diastolic bp ≥ 95 mm hg and sitting systolic bp ≥ 155 mm hg) as well as hr\>90 bpm * known hiv infection (no tests required) * clinically significant or potentially disabling eye disorder, including uncontrolled glaucoma * serologic evidence of active hepatitis b and/or c * history of cancer within the past 5 years, excluding treated basal cell carcinoma * subjects previously treated with tesofensine * subjects treated with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study drug