E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Aid to smoking cessation in cigarette smokers |
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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 | 10057852 |
E.1.2 | Term | Nicotine dependence |
|
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 assess the dose effect relationship of three fixed doses of surinabant on abstinence from smoking in cigarette smokers during the last four weeks of treatment. |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the dose effect relationship of surinabant on change of body weight. • To evaluate the clinical and biological safety and tolerability of surinabant. • To evaluate the dose effect relationship of surinabant on urges for nicotine. • To measure the plasma trough levels of surinabant. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients over legal age, smoking at least 10 cigarettes/day as a mean within the 6 months preceding the screening visit. |
|
E.4 | Principal exclusion criteria |
Related to study methodology 1. Level of motivation to quit less than 6 on a ten-point Likert Scale. 2. Refusal or inability to give informed consent to participate in the study. 3. Not able to follow verbal and written instructions and to complete all aspects of the study. 4. Other participant in a household enrolled in the study. 5. Patients who have a history of multiple allergic reactions to medications in two drug classes. 6. Patients who have taken an investigational drug within the past 6 months prior to the screening visit. 7. Patients who have smoked or consumed non-tobacco cigarettes or any form of tobacco product (other than cigarettes such as cigars, pipes, smokeless tobacco, etc) more than 3 days within the 3 months preceding the screening visit. 8. Patients dependent to alcohol or illicit drugs. 9. Patients who have smoked or consumed marijuana in any form on more than one occasion during the past 3 months. 10. Presence of any clinically significant current acute or chronic unstable neurological, gastrointestinal, cardiovascular, renal, hematological, endocrine, dermatological or respiratory disease, or any other medical condition including that might interfere with the evaluation of study medication. 11. Patients with a lifetime diagnosis (based on DSM-IV) of Psychotic Disorder. 12. Patients who currently present with (based on DSM-IV) a Major Depressive Episode (unstable and/or treated efficiently by an antidepressant since less than 6 months). 13. Patients who have suffered from a myocardial infarction, unstable angina or other major cardiovascular event within the past 6 months prior to screening. 14. Subjects who have an ECG abnormality, detected at screening and confirmed by repeated test, which is clinically significant according to the investigator, including a QT interval with Fridericia's correction (QTcF) ≥ 500 msec. 15. Pregnant or breast-feeding women. 16. Women of childbearing potential not protected by effective contraceptive method of birth control and/or who are unwilling or unable to be tested for pregnancy. Medically acceptable methods of birth control for this study include approved hormonal contraceptive medications or devices, approved intra-uterine contraceptive devices, use of two combined barrier methods.
Related to surinabant 17. Treatment with CYP3A4 potent inhibitors, see list given in Appendix A of the protocol. If previously administered, the patient should have stopped taking these drugs at least 4 weeks prior to randomization. Patients receiving other inhibitors of CYP3A4 can be included but therapeutic substitution should be considered whenever possible. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy criterion for this trial is the continuous abstinence from tobacco smoking at every visit during the last four weeks of the treatment period, i.e. from D29/W5 to D56/W8.
Abstinence will be defined by concurrence of the following components: • Smoking status Through direct inquiry of the patient, using daily recording from the patient, the investigator will determine whether the patient has been continuously abstinent (or nonabstinent) from tobacco cigarette smoking since the previous scheduled visit.
and
• Carbon Monoxide Exhaled carbon monoxide (CO) testing will be performed as a biomedical marker of smoking status. To be considered abstinent, the patient must have a level of exhaled CO ≤ 10 ppm Technical procedures for collection of exhaled CO will be described in a separate manual to be provided to the investigational sites.
and (when measured)
• Cotinine measurements (only assessed at D35/W5 and D56/W8) To confirm smoking status and exhaled CO results, plasma cotinine measurements will be performed. In order to be considered to be abstinent from nicotine, a patient must have plasma cotinine levels of less than or equal to 8 micrograms/L. A validated LC-MS/MS method with a limit of quantification of 4 ng/ml for cotinine will be used. Analysis will be conducted within the Department of Metabolism and Pharmacokinetics, sanofi-aventis Research, Malvern, PA 19355, USA. Technical procedures for collection, handling, storage and shipment of cotinine samples will be described in a separate manual to be provided to the investigational sites. |
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 29 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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
| |
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 | 1 |
E.8.9.1 | In the Member State concerned days | 10 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 10 |