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:

* Participants must have stable, documented cardiovascular disease (including at least one of the following diagnosed \> 2 months prior to the Screening visit - angina, myocardial infarction (MI), revascularization, transient ischemic attack (TIA), and peripheral vascular disease (PVD).
* Participants that smoke \> 10 cigarettes / day.

Exclusion Criteria:

* Participants with unstable cardiovascular disease
* Cardiovascular events in the past 2 months
* Moderate or severe chronic obstructive pulmonary disease (COPD)
B: Inclusion Criteria:

1. Male or non-pregnant female cigarette smokers 18-years-of-age or older and reporting smoking at least an average of 10 cigarettes per day for the past year;
2. Subject is alcohol dependence based on DSM IV criteria as assessed by the Mini-International Neuropsychiatric Interview (MINI) and the physician investigator;3
3. Subject is currently drinking alcoholic beverages as assessed by the physician investigator;
4. Subject is a female subject of non-childbearing potential or a female subject of childbearing potential - who is using contraceptives and has a negative pregnancy test result;
5. Subject must be able to complete all the study visits;
6. Subject has the ability to participate fully in all aspects of the study and keep scheduled appointments;
7. Subject must be in good general health as determined by medical history, physical exam and physician investigator;
8. Subject must provide written informed consent to participate in the study;

Exclusion Criteria:

1. Subject is a female who is pregnant, lactating or likely to become pregnant during the trial and not willing to use an acceptable form of contraception during the medication phase, (for women of child-bearing potential, a pregnancy test will be performed prior to entry into the study and at the end of the medication phase);
2. Subject has another household member in study;
3. Known allergy to varenicline;
4. Subject is currently (in previous 30 days) using other behavioral or pharmacologic tobacco cessation program (i.e., behavioral therapy, nicotine replacement therapy, clonidine, varenicline, bupropion SR, nortriptyline or doxepin) and unwilling or unable to discontinue use;
5. Subject has an unstable medical condition as determined by the physician investigator;
6. Subject describes having a medical history of: a) unstable angina; b) myocardial infarction within the past 3 months; c) coronary angioplasty or d) an untreated cardiac dysrhythmia;
7. Subject has a personal history of renal failure or is on renal dialysis;
8. Subject has a current moderate or severe depression as assessed by the Center for Epidemiologic Studies-Depression survey (CES-D) and physician investigator;
9. Subject has, as defined by the Columbia Suicide Severity Rating Scale (C-SSRS) current non-specific suicidal thoughts, or have a 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");
10. Subject has current (past 30 days) major depressive disorder or has a history of another psychiatric disorder such as psychosis or bipolar disorder;
11. Subject currently uses of other tobacco products (i.e. pipe, cigar, smokeless tobacco) within the past 30 days;
12. Subject currently has cancer \[excluding non melanoma skin cancer\] not in remission (cancer free for 5 years or more);
13. Subject currently has Type 1 diabetes;
14. Subject has untreated hypertension or baseline systolic blood pressure \> 180 or diastolic \> 100;
15. Subject is currently on treatment with another investigational drug (within 30 days of study entry);
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. be male or female, 18 years of age or older
2. be able to understand the study, and having understood, provide written informed consent in English
3. have been enrolled in the University of Cincinnati Physicians Company-Opioid Treatment Program (UCPC-OTP) program for at least 30 days and be stable on the current methadone dose for at least 1 week
4. have smoked cigarettes for at least 3 months, have a measured exhaled carbon monoxide (CO) level \> 8 parts per million (ppm), and not planning to seek smoking-cessation treatment within the next 3 months
5. have a willingness to comply with all study procedures, including trying to stop smoking during designated weeks, and to comply with medication instructions
6. based on a week of Quitbit cigarette lighter assessments, with at least 5 days of usable data, smoke ≥ 10 cigarettes/day and smoke at least 30% of daily cigarettes within the 4-hour post-methadone-dosing period
7. if female and of child bearing potential, agree to use one of the following methods of birth control: oral contraceptives, contraceptive patch, barrier (diaphragm or condom), intrauterine contraceptive system, levonorgestrel implant, medroxyprogesterone acetate contraceptive injection,complete abstinence from sexual intercourse, hormonal vaginal contraceptive ring.

Exclusion Criteria:

1. have a current or past diagnosis of any psychotic disorder, or bipolar I or II disorder
2. have a psychiatric condition that, in the judgment of the study physician would make study participation unsafe or which would make treatment compliance difficult
3. be a significant suicidal/homicidal risk
4. have a medical condition that, in the judgment of the study physician, would make study participation unsafe or which would make treatment compliance difficult. Such conditions include, but are not limited to:

   * liver function tests greater than 3 times upper limit of normal
   * serum creatinine greater than 2 mg/dL
5. have had clinically significant cardiovascular or cerebrovascular disease within the past 6 months or have clinically significant ECG abnormalities
6. have taken an investigational drug within 30 days before consent
7. be taking concomitant medications that are contraindicated for use with the NNS or varenicline
8. be taking any concomitant medications that could increase the likelihood of smoking cessation (such as wellbutrin or nortriptyline)
9. have a known or suspected hypersensitivity to varenicline or the nicotine nasal spray (NNS)
10. use/have used smoking-cessation counseling programs with individual counseling or smoking-cessation medication treatments currently, or within 30 days before consent
11. have used electronic cigarettes or tobacco products, other than cigarettes, in the week before consent
12. be pregnant or breastfeeding
13. be anyone who, in the judgment of the investigator, would not be expected to complete the study protocol (e.g., due to relocation from the clinic area, probable incarceration, etc.)

Answer: C