Clinical trial NCT00394667 (phase 2, status: completed)
Conditions: obesity
ICD codes: E66.8, E66.9, E66.1, O99.214, O99.215, O99.210, O99.211
Drugs: tesofensine
SMILES: CCOC[C@H]1[C@H]2CC[C@@H](C[C@@H]1C1=CC(Cl)=C(Cl)C=C1)N2C
Eligibility criteria:

        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