Effect of Tesofensine on Weight Reduction in Patients With Obesity.

Study Overview
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Brief Summary
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Purpose: To evaluate the efficacy on weight reduction, metabolic parameters and safety of tesofensine versus placebo in obese patients

Official Title
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Effect of Tesofensine on Weight Reduction in Patients With Obesity. A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multi-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: Obese patients with 30 kg/m² ≤ BMI ≤ 40 kg/m² Males and females 18 to 65 years of age, extremes included Patients continuously receiving diet therapy as well as instructions on exercise at least for 2 weeks run-in, who during the run-in before randomization do not gain weight (< 2 kg) Females of childbearing potential must be non-pregnant and use safe contraceptive methods (the pill, IUD or surgically sterilized) Patients should be able to comply with study procedures Smoking habits should have been stable for at least 2 months Patients giving written informed consent Exclusion Criteria: Use of prescription medication as listed Positive serum pregnancy test for women of childbearing potential Pregnant or lactating women, or women who are planning to become pregnant within the next 8 months Patients with specific diseases interfering with their metabolism e.g. untreated myxoedema, Cushing's syndrome, Type 1 diabetes mellitus, significant neurological or psychiatric illness such as epilepsy, schizophrenia, depression, eating disorders such as bulimia. Patients 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 Patients currently (within the past 2 months) known to abuse or to be dependent on any drug, including alcohol (weekly consumption > 21 units of alcohol (men) or >14 units of alcohol (women)) 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) Known untreated hypercholesterolaemia (> 7 mmol/l). Patients with well regulated cholesterol using drugs for hypercholesterolaemia are allowed inclusion Known untreated hypertriglyceridaemia (> 3 mmol/l). Patients with well regulated triglyceride levels using drugs for hypertriglyceridaemia are allowed inclusion Drug treated thyroid diseases (well substituted hypothyroidism is allowed) Patients who suffer from hyperthyroid disease are not allowed in the study, even though they may be well treated by drugs Patients, who have recently diagnosed, not yet stable hypothyroid disease are not allowed in the study Patients who suffer from longstanding stable hypothyroid disease, well treated substitution are allowed to be included including hypothyroidism as a sequelae to definitive treatment of hyperthyroidism by surgery or radioactive iodine Malabsorptive intestinal disorders that can be assumed to affect the absorption of tesofensine Special diets (e.g., vegetarian, Atkins) Patients 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 Mental or psychiatric disorder based on medical history only Surgically treated obesity Patients with systemic infections or inflammatory diseases 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 > 480 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 Uncontrolled hypertension (i.e. sitting diastolic BP ≥ 95 mm Hg and sitting systolic BP ≥ 155 mm Hg) despite treatment for > 4 weeks prior to the screening visit as well as HR>90 bpm Known HIV infection (no tests required) Serologic evidence of active hepatitis B and/or C History of cancer within the past 5 years, excluding treated basal cell carcinoma Clinically significant or potentially disabling eye disorder, including uncontrolled glaucoma Current treatment with medication with known ocular toxicity such as chloroquine and hydroxychloroquine is prohibited Patients previously treated with tesofensine Patients 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: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

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 |
| --- | --- | --- |
| Percent change and absolute change in body weight |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Waist circumference, waist-hip ratio, change in BMI, Sagittal diameter and DEXA |  |  | 
| blood tests (Triglycerides, Cholesterol-total, LDL-C, HDL-C, LDH, Blood glucose fasting, HbA1c, C-reactive protein, Insulin and Adiponectin ) |  |  | 
| data from questionnaires (Baecke Questionnaire, Satiety & Appetite Questionnaire, POMS, and Impact of Weight on Quality of Life Questionnaire -Lite Version (IWQOL-Lite)) |  |  | 
| Safety & Tolerability |  |  |