Please select the eligibility criteria that correspond to the clinical trial below.
Title: Combination Therapy With Varenicline and Bupropion for Smoking Cessation
Brief Summary: This study provides an opportunity to combine varenicline and bupropion SR and capitalize on the potential additive benefit. The investigators hypothesize that this will further increase long-term (≥ 6 months) smoking abstinence rates.


Options:
A: Inclusion Criteria:

* Men or women aged ≥18 years
* Currently smoking 10 cigarettes per day or more
* Having smoked 5 py or more
* Presenting a CO level in expired air ≥ 10 ppm
* Personally motivated to reduce or stop smoking and indicating a willingness to follow through with protocol requirements
* Willing to sign a statement of informed consent

Exclusion Criteria:

* Myocardial infarction within the last 3 months
* Unstable angina
* Severe cardiac arrhythmia
* Pregnancy or breast feeding
* Use of any form of smokeless tobacco or nicotine substitution
* Having followed any smoking cessation programme during the last 3 months
* Alcohol or other drug addiction
* Use of any form of smokeless tobacco or nicotine substitution
* Participation in any clinical trial within the past 3 months
* Women in childbearing age not willing to use contraception until week 12 after QD
B: Inclusion Criteria:

* Smoke 3-30 cigarettes/day
* Desire to quit smoking as indicated on a smoking stages ladder
* Consume \>14 (men) or \>7 (women) standard alcohol drinks per week (e.g., 1 drink = 12 oz beer, 5 oz wine, 1.5 oz liquor)
* Ability to understand, read, and write in English, at least 8th grade education
* Willing and able to sign an informed consent
* Stable residence and contact information.

Exclusion Criteria:

* Hepatic panel indices \> 2 SD
* History of seizures or DTs during alcohol withdrawal
* Unstable medical (e.g., hepatitis, cirrhosis, seizure disorder, recent major cardiovascular event, etc.) or psychiatric disorder (e.g., active hallucinations, severe depression, obsessional thinking, self-injury risking significant blood loss, etc.) deemed by the study physician to be at significant risk for adverse interactions with study medications or measures.
* History of adverse reactions to varenicline (VAR) or nicotine patch
* Current suicidal ideation (past 6 months) and/or history of major suicide attempts.
* For women of child-bearing potential: currently pregnant, lactating, current plans to become pregnant in next three months, or unable to agree to adequate birth control during study participation.
C: Inclusion Criteria:

1. Subject is at least 18 years of age;
2. Subject has provide written informed consent;
3. Subject is smoking greater than or equal to 10 cigarettes per day for at least 6 months;

3) Subject is able to complete all study visits 4) Subject is in good health as determined by the investigator 5) Subject has the ability to participate fully in all aspects of the study and keep scheduled appointments 6) Subject is motivated to stop smoking.

Exclusion Criteria:

Female and were pregnant, lactating or likely to become pregnant during the trial and not able nor willing to use contraception or had:

1. an unstable medical condition;
2. another household member participating in the study;
3. bupropion or varenicline allergy;
4. current use (previous 30 days) of a tobacco dependence treatment and unable or unwilling to discontinue use;
5. an unstable medical condition or unstable angina, myocardial infarction, or coronary angioplasty (past 3 months) or an untreated cardiac dysrhythmia;
6. a history of renal failure or were on renal dialysis;
7. a history of seizures;
8. as defined by the C-SSRS (Columbia-Suicide Severity Rating Scale), current non-specific suicidal thoughts or lifetime history of a suicidal attempt (defined as "potentially self-injurious act committed with at least some wish to die, as a result of act");
9. a history of closed head trauma associated with \> 30 minutes of loss of consciousness, amnesia, skull fracture, subdural hematoma, or brain contusion;
10. a history or psychosis, bipolar disorder, bulimia or anorexia nervosa;
11. current moderate or severe depression as assessed by a score of ≥ 20 on the Beck Depression Inventory, Second Edition (BDI-II) 10;
12. active substance abuse other than nicotine;
13. current (past 14 days) use of an antipsychotic, monoamine oxidase inhibitors, or drugs known to interact with bupropion SR;
14. a recent dose change of their antidepressant (within last 3 months);
15. untreated hypertension or baseline systolic blood pressure \> 180 or diastolic \> 100;
16. current treatment with another investigational drug for tobacco dependence (previous 30 days); or
17. current use of bupropion or varenicline (previous 30 days).
D: Inclusion Criteria:

1. Smokers smoking at least 10 cigarettes/day (factory made or roll-your-own) in the past year
2. Aged 18 to 70 years
3. Motivated to quit defined as a score \> 5 on a visual rating scale ranging from 0 (not motivated at all) to 10 (extremely motivated)
4. Signed written informed consent
5. Understanding and speaking French
6. Women of childbearing age can be included if they use an effective contraceptive method: either hormonal contraception or an intrauterine device started at least one month before the first research visit
7. Individual affiliated to a health insurance system as defined by the sponsor (except Aide Médicale d'État =AME)
8. Previous failure of nicotine replacement therapy for smoking cessation

Exclusion Criteria:

1. any unstable disease condition within the last 3 months defined by the investigator as major change in symptoms or treatments such as 1.1.recent myocardial infarction, 1.2.unstable or worsening angina 1.3.severe cardiac arrhythmia 1.4.unstable or uncontrolled arterial hypertension 1.5.recent stroke 1.6.cerebrovascular disease 1.7.obliterative peripheral arterial disease 1.8.cardiac insufficiency 1.9.diabetes 1.10.hyperthyroidism 1.11.pheochromocytoma 1.12.severe hepatic insufficiency 1.13.history of seizures 1.14.severe depression 1.15.chronic obstructive pulmonary disease (COPD)
2. any life threatening condition with life-expectancy of less than 3 months
3. alcohol use disorder defined as a score ≥ 10 on the AUDIT-C questionnaire
4. abuse of or dependence on illegal drugs in the last 6 months revealed by the medical history
5. regular use of tobacco products other than cigarettes
6. current or previous (last 6 months) use of electronic cigarette
7. pregnant women
8. breastfeeding women
9. protected adults
10. current or past 3 months participation in another interventional research
11. current or past (last 3 months) use of smoking cessation medication such as varenicline, bupropion, nicotine replacement therapies
12. known lactose intolerance (placebo tablets contain lactose)
13. hypersensitivity to the active substance or to any of the excipients
14. known severe renal failure

Answer: C