Evaluation of Long Term Safety of Tesofensine in Patients With Obesity

Evaluation of Long Term Safety of Tesofensine in Patients With Obesity

Purpose of the study is to evaluate the long term safety of tesofensine in obese patients

Inclusion Criteria:

Patients who have completed their participation in TIPO-1

• Males and females 18 to 65,5 years of age, extremes included
• Patients continuously receiving diet therapy as well as instructions on exercise
• Females of childbearing potential must be non-pregnant and use safe contraceptive methods (the pill, IUD, injection of prolonged gestagen, sub dermal implantation, hormonal vaginal devices, transdermal patches or surgically sterilized)
• Patients should be able to comply with study procedures
• Patients giving written informed consent

Exclusion Criteria:

• Patients with a BMI< 22
• Use of prescription medication as listed in Appendix 1
• Positive pregnancy test for women of childbearing potential
• Pregnant 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 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
• 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) in females and >450 ms in males, 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)
• 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 treated with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study drug