Clinical trial NCT00428415: Effect of Tesofensine on Energy Balance in Humans.
Official title: The Effect of Tesofensine on Energy Balance in Humans. A Randomised, Double-Blind, Placebo-Controlled, Parallel- Group, Single Centre Study.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Obesity
Lead sponsor: NeuroSearch A/S
Sponsor class: INDUSTRY
First posted: 2007-01-30
Enrollment: 32
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Purpose:

To evaluate the effect of tesofensine on energy balance


Eligibility criteria: Inclusion Criteria:

* Overweight to obese subjects with BMI 28 - 35 kg/m² otherwise healthy
* Males 18 to 50 years of age, extremes included
* Subjects should be able to comply with study procedures
* Subjects giving written informed consent

Exclusion Criteria:

* Use of any concomitant medication including high dose vitamins and regular OTC preparations
* Subjects who have been smokers within the last year
* Subjects with specific diseases interfering with their metabolism e.g. myxoedema, Cushing's syndrome, Type 1 diabetes mellitus, significant neurological or psychiatric illness such as epilepsy, schizophrenia, depression, eating disorders such as bulimia.
* Subjects 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
* Known hypercholesterolaemia (\> 7 mmol/l).
* Known hypertriglyceridaemia (\> 3 mmol/l).
* Malabsorptive intestinal disorders that can be assumed to affect the absorption of tesofensine
* Mental or psychiatric disorder based on medical history only
* Subjects with systemic infections or inflammatory diseases
* Subjects currently (within the past 2 months) known to abuse or to be dependent on any drug, including alcohol (weekly consumption \> 21 units of alcohol )
* 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)
* Special diets (e.g., vegetarian, Atkins)
* Subject should not be athletics or 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
* Surgically treated obesity
* 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 \> 450 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
* Hypertension (i.e. sitting diastolic BP ≥ 95 mm Hg and sitting systolic BP ≥ 155 mm Hg) as well as HR\>90 bpm
* Known HIV infection (no tests required)
* Clinically significant or potentially disabling eye disorder, including uncontrolled glaucoma
* Serologic evidence of active hepatitis B and/or C
* History of cancer within the past 5 years, excluding treated basal cell carcinoma
* Subjects previously treated with tesofensine
* Subjects 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: Effect on 24-h EE (energy expenditure) after 14 days dosing, adjusted for FFM(Fat-Free Mass) and FM (Fat Mass) changes
Secondary outcomes:
measure: 24-h fat oxidation, spontaneous physical activity, fecal excretion of energy and fat (respiratory chamber),Changes in body weight and composition
measure: Physical Measure(Waist circumference, waist-hip ratio, change in BMI, Sagittal diameter and DEXA, Spontaneous energy intake at lunch test
measure: Metabolic measures (Total triglycerides, Cholesterol-total, LDL-C, HDL-C, LDH, Blood glucose fasting, HbA1c, C-reactive protein, Insulin, Adiponectin, FFA, CCK, Ghrelin, and Leptin)
measure: Data from questionnaires( Satiety & Appetite, POMS Brief)
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: