E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Psychiatry and Psychology [F] - Behaviours [F01] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008374 |
E.1.2 | Term | Cessation of smoking |
E.1.2 | System Organ Class | 100000004869 |
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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 assess in heavy smokers willing to quit smoking the efficacy and the safety profile of BP1.4979 for smoking cessation on the total abstinence measured by subject diary and confirmed by exhaled CO (abstinent ≤ 10 ppm). |
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E.2.2 | Secondary objectives of the trial |
No secondary objectives were established |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. males or females, aged 18 to 65 years old 2. 18 kg/m2 ≤ BMI ≤ 35 kg/m2 3. a smoking history of at least 10 years 4. subject smoking at least 15 cigarettes per day at the time being and for at least 30 days before selection. 5. motivated to quit smoking with a motivation test score > 12 on the Legeron and Lagrue Questionnaire of Motivation (Q-MAT) at the selection and at the inclusion 6. having already made at least 2 attempts to stop (each of at least 7 days), including at least one attempt with medical and pharmacological treatment, at least 30 days before the selection 7. with no period of abstinence > 3 months in the previous year 8. Fagerström Test of Nicotine Dependence (FTND) 7 at V0 (screening) and/or at V1 (randomization) 9. not taking anti-smoking medication 10. not taking antipsychotic medication, antidepressant except Selective Serotonin Reuptake Inhibitors (SSRIs) prescribed for at least one month (e.g. fluoxetine, paroxetine, fluvoxamine, sertraline, citalopram, escitalopram, venlafaxine, milnacipran, duloxetine) and/or any other psychotropic medication except benzodiazepine treatment stable for at least one month prior to inclusion in the study. 11. females of child-bearing potential must use a medically accepted effective method of birth control, agree to continue this method for the duration of the study and be negative to serum pregnancy test performed at the screening visit. Females should not be breast-feeding subject. 12. in the opinion of the investigator, the subject must have adequate support to comply with the entire study requirements as described in the protocol (e.g. transportation to and from trial site, self rating scales, drug compliance, scheduled visits, etc). 13. subject must have voluntarily expressed willingness to participate in this study, understand protocol procedures and have signed and dated an informed consent prior to beginning any protocol required procedures. 14. attend usual smoking cessation counseling provided by investigator. |
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E.4 | Principal exclusion criteria |
1. any significant psychiatric illness (schizophrenia, bipolar disorder, severe depression, dementia...) or mood disorder, assessed by the Beck Depression Inventory (BDI) (exclusion if 8 and/ or item G ≠ 0). 2. Hospital Anxiety and Depression (HAD) scale (A + D ≥ 19, the day of the selection and inclusion). 3. substance use disorder (except nicotine). 4. Alcohol Use Disorders Identification Test (AUDIT) 8. 5. any use of non prescription opiates / stimulants (amphetamines), cocaine or cannabis in the 3 previous months. 6. positive urinary test on opiates, amphetamine, cannabis or cocaine. 7. other active clinically significant illness, including unstable cardiovascular, or neoplasic pathology which could interfere with the study conduct or counter-indicate the study treatments or place the subject at risk during the trial or compromise the study participation. 8. subject with a known history of long QTc syndrome (e.g. syncope or arrhythmia) or presenting any significant serious abnormality of the ECG (e.g. recent myocardial infarction), or QTcB interval strictly higher than 450 ms for man and 460 ms for woman (electrocardiogram Bazett's corrected QT interval: QTc=QT/ [60/HR]). 9. subject with severe hepatic impairment or with severe renal impairment, or with any other significant abnormality in the physical examination or clinical laboratory results (e.g positive laboratory test for Hepatitis B surface antigen (HBsAg), or anti-HIV 1/2 or anti- HCV antibodies). 10. known hypersensitivity to the tested treatment including active substance and excipients. 11. subject smoking cigars or pipes in addition to cigarettes (patient should have stopped cigars or pipes at least 30 days before V0) 12. subject taking any antismoking medication (e.g. bupropion, varenicline, clonidine, cytisine..), and/ or Nicotine Replacement Therapy (NRT) in the previous month. 13. subject taking antipsychotic medication, or antidepressants other than SSRIs (SSRIs taking for at least one month). 14. subject taking anxiolytics (except benzodiazepines at stable dose for at least 1 month). 15. subject taking any prescription drug containing amphetamines. 16. subject on anti smoking targeted Cognitive Behavioral Therapy (CBT) or any antismoking oriented psychotherapy or acupuncture or using an electronic cigarette. 17. subject participating in another study and the use of any investigational therapy within the 30 days prior to the entry in this study. 18. subject without any medical care insurance. 19. pregnant woman or a pregnancy detected with a positive serum pregnancy test performed at the screening visit. 20. male subject who wants to conceive a child for the whole duration of the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary measure of efficacy will be 4-week prolonged abstinence from smoking cigarettes at the end of 12-week double-blind treatment phase (i.e. from V3 to V4). The continuous abstinence measured by subject diary and verified by exhaled CO (abstinent < 10 ppm) will define response to the treatment.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During treatment phase and up to 3 months after treatment. |
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E.5.2 | Secondary end point(s) |
•7-day tobacco Point Prevalence Abstinence (PPA) will be assessed at each visit by analysis of cigarettes consumption using self-report diaries and measurement of exhaled CO •daily cigarettes consumption (Measure: mean consumption variation to baseline to determine % of subjects having reduced cigarettes consumption between baseline and last week of treatment.) •assessment of craving and urge to smoke performed at each visit except screening (V0) by QSU-Brief Questionnaire (Measure: variation from V1 to V2, V3, V4, V5 and V-TQD), on (7-days PPA) responders •continuous abstinence from V3 (W8) to V6 (W16) and from V3 (W8) to V8 (W24) •nicotine withdrawal syndrome assessed by Minnesota Nicotine Withdrawal Scale (MNWS) (assessing urge to smoke, depressed mood, irritability, anxiety, poor concentration, restlessness, increased appetite and insomnia). (Measure: variation from V1 to V2, V3, V4, V5 and V-TQD ), on (7-days PPA) responders •smoking satisfaction measured by the modified Cigarette Evaluation Questionnaire (mCEQ) (recording measures of smoking satisfaction, psychological reward, enjoyment of respiratory tract sensations, craving reduction and aversion) if the subject continue to smoke. (Measure: variation from V1 to V2, V3, V4, V5 and V-TQD), in patients still smoking. •body weight variation in treatment responders •BDI mean depressive score variation in responders •abstinence in a sub-group of subjects having TQD up until treatment Day 8 •safety will be assessed by evaluation of adverse events, various questionnaires and vital signs (measurement of heart rate, blood pressure, and body weight) at each study visit, by physical examinations (V0 and V4), ECG and laboratory tests (blood chemistry, haematology, urinanalysis tests, prolactin dosage) at screening (V0), after 4-week treatment (V2) and at V4. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Throughout the whole study duration. |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
1 additional PL1 week single-blind for each patient at the 12th week. |
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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.8.2.4 | Number of treatment arms in the trial | 5 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 19 |
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 | No |
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 | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |