Effect of Tesofensine on Energy Balance in Humans.

The Effect of Tesofensine on Energy Balance in Humans. A Randomised, Double-Blind, Placebo-Controlled, Parallel- Group, Single Centre Study.

Purpose:

To evaluate the effect of tesofensine on energy balance

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