Effect of Tesofensine on Weight Reduction in Patients With Obesity.

Effect of Tesofensine on Weight Reduction in Patients With Obesity. A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multi-centre Study.

Purpose:

To evaluate the efficacy on weight reduction, metabolic parameters and safety of tesofensine versus placebo in obese patients

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