Clinical trial NCT00394667: Effect of Tesofensine on Weight Reduction in Patients With Obesity.
Official title: Effect of Tesofensine on Weight Reduction in Patients With Obesity. A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multi-centre Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obesity
Lead sponsor: NeuroSearch A/S
Sponsor class: INDUSTRY
First posted: 2006-11-01
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Purpose:

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


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

Primary outcomes:
measure: Percent change and absolute change in body weight
Secondary outcomes:
measure: Waist circumference, waist-hip ratio, change in BMI, Sagittal diameter and DEXA
measure: blood tests (Triglycerides, Cholesterol-total, LDL-C, HDL-C, LDH, Blood glucose fasting, HbA1c, C-reactive protein, Insulin and Adiponectin )
measure: data from questionnaires (Baecke Questionnaire, Satiety & Appetite Questionnaire, POMS, and Impact of Weight on Quality of Life Questionnaire -Lite Version (IWQOL-Lite))
measure: Safety & Tolerability
Other outcomes:
Locations:
city: Ballerup
country: Denmark
facility: NeuroSearch A/S
Study officials:
affiliation: Department of Human Nutrition, The Royal Veterinary & Agricultural University
name: Arne V Astrup, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Expression of concern--effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet. 2013 Apr 6;381(9873):1167. doi: 10.1016/S0140-6736(13)60778-3. No abstract available.
citation: Gilbert JA, Gasteyger C, Raben A, Meier DH, Astrup A, Sjodin A. The effect of tesofensine on appetite sensations. Obesity (Silver Spring). 2012 Mar;20(3):553-61. doi: 10.1038/oby.2011.197. Epub 2011 Jun 30.
citation: Astrup A, Madsbad S, Breum L, Jensen TJ, Kroustrup JP, Larsen TM. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet. 2008 Nov 29;372(9653):1906-1913. doi: 10.1016/S0140-6736(08)61525-1. Epub 2008 Oct 22.