Effect of Tesofensine on Energy Balance in Humans.

Study Overview
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Brief Summary
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Purpose: To evaluate the effect of tesofensine on energy balance

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

Conditions
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Obesity

Intervention / Treatment
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* Drug: Tesofensine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Tesofensine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect on 24-h EE (energy expenditure) after 14 days dosing, adjusted for FFM(Fat-Free Mass) and FM (Fat Mass) changes |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-h fat oxidation, spontaneous physical activity, fecal excretion of energy and fat (respiratory chamber),Changes in body weight and composition |  |  | 
| Physical Measure(Waist circumference, waist-hip ratio, change in BMI, Sagittal diameter and DEXA, Spontaneous energy intake at lunch test |  |  | 
| Metabolic measures (Total triglycerides, Cholesterol-total, LDL-C, HDL-C, LDH, Blood glucose fasting, HbA1c, C-reactive protein, Insulin, Adiponectin, FFA, CCK, Ghrelin, and Leptin) |  |  | 
| Data from questionnaires( Satiety & Appetite, POMS Brief) |  |  | 
| Safety & Tolerability |  |  |