Condition(s) treated: Obesity

Intervention: Tesofensine (Drug)

Phase: Phase 2

Enrollment status: Recruiting. Expecting to enroll 200 people.

Sponsor: NeuroSearch A/S

Principal investigator(s) or official(s):
Arne V Astrup, MD, Principal Investigator, Affiliation: Department of Human Nutrition, The Royal Veterinary & Agricultural University

Overall contact:
Dieter H Meier, MD, Phone: 45 44 60 82 67, Email: dhm@neurosearch.dk

Purpose:

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

Official title: Effect of Tesofensine on Weight Reduction in Patients With Obesity. A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Multi-Centre Study.

Study design: Interventional, Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Percent change and absolute change in body weight

Secondary outcome: 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

Minimum eligible age: 18 Years. Maximum eligible age: 65 Years. Eligible gender(s): Both.

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

Dieter H Meier, MD, Phone: 45 44 60 82 67, Email: dhm@neurosearch.dk

NeuroSearch A/S, Ballerup 2750, Denmark; Recruiting

Start date: September 2006
End date: October 2007
Last updated: October 31, 2006