E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 8.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10029883 |
E.1.2 | Term | Obesity |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy on weight reduction, metabolic parameters and safety of tesofensine versus placebo in obese patients. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Males and females 18 to 65 years of age, extremes included 2. Patients continuously receiving diet therapy as well as instructions on exercise at least for 2 weeks run-in, who during the run-in before randomisation do not gain weight ( < 2 kg) 3. Females of childbearing potential must be non-pregnant and use safe contraceptive methods ( the pill, IUD or surgically sterilized) 4. Patients should be able to comply with study procedures 5. Smoking habits should have been stable for at least 2 months 6. Patients giving written informed consent
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E.4 | Principal exclusion criteria |
1. Use of prescription medication 2. Positive serum pregnancy test for women of childbearing potential 3. Pregnant or lactating women, or women who are planning to become pregnant within the next 18 months 4. 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. 5. 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. 6. 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)) 7. 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) 8. Known untreated hypercholesterolaemia (> 7 mmol/l). Patients with well regulated cholesterol using drugs for hypercholesterolaemia are allowed inclusion. 9. Known untreated hypertriglyceridaemia (> 3 mmol/l). Patients with well regulated triglyceride levels using drugs for hypertriglyceridaemia are allowed inclusion. 10. Drug treated thyroid diseases (well substituted long standing hypothyroidism is allowed, including hypothyroidism as a sequelae to definitive treatment of hyperthyroidism by surgery or radioactive iodine) 11. Special diets (e.g., vegetarian, Atkins) 12. Malabsorptive intestinal disorders that can be assumed to affect the absorption of tesofensine 13. 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 14. Surgically treated obesity 15. Weight change of > 3 kg within 2 months prior to screening 16. Mental disorders or psychiatric disorder based on medical history only 17. Patients with systemic infections or inflammatory diseases 18. History or presence of significant cardiovascular disease such as heart failure, ischemic heart disease, stroke, transient ischemic attacks 19. 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 20. 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 21. 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. 22. Known HIV infection (no tests required) 23. Serologic evidence of active hepatitis B and/or C 24. History of cancer within the past 5 years, excluding treated basal cell carcinoma 25. Clinically significant or potentially disabling eye disorder, including uncontrolled glaucoma 26. Current treatment with medication with known ocular toxicity such as chloroquine and hydroxychloroquine is prohibited 27. Patients previously treated with tesofensine 28. Patients treated with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding the first dose of study drug |
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E.5 End points |
E.5.1 | Primary end point(s) |
Absolut change and percent change in body weight from baseline to end of treatment at week 24.
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |