Please select the eligibility criteria that correspond to the clinical trial below.
Title: Concurrent Bupropion / Varenicline for Smoking Cessation
Brief Summary: This study focuses on the first step in developing an algorithm for maximizing quit-smoking success based on an adaptive approach, which changes treatment from the initial nicotine replacement therapy (NRT) when that treatment alone may not be sufficient. These NRT "non-responders" are switched (in double-blind fashion) before the quit date to receive either varenicline alone or varenicline paired with bupropion. Some participants who would otherwise have failed at their quit smoking attempt could be "rescued" by switching to alternative pharmacotherapies. The proposed study will evaluate the combination treatment against varenicline alone in an adaptive trial design


Options:
A: Inclusion Criteria:

* Cigarette smokers who are motivated to stop smoking and have smoked an average of at least 10 cigarettes per day

Exclusion Criteria:

* Subjects who have used a nicotine replacement product within 30 days of the study screening visit or intend to use it during the study.
B: Inclusion Criteria:

* 18-65 years old;
* smoked an average of at least 10 cigarettes per day for three cumulative years;
* have an expired air CO reading assessed at screening of at least 10ppm;
* express a desire to quit smoking within the next 30 days.

Exclusion Criteria:

* Hypertension (systolic \>140 mm Hg, diastolic \>100 mm Hg, coupled with a history of hypertension); subjects with no previous diagnosis of hypertension may have a screening blood pressure up to 160/100.
* Hypotension with symptoms (systolic \<90 mm Hg, diastolic \<60 mm Hg).
* Coronary heart disease;
* Lifetime history of heart attack;
* Cardiac rhythm disorder (irregular heart rhythm);
* Chest pains (unless history, exam, and ECG clearly indicate a non-cardiac source);
* Cardiac (heart) disorder (including but not limited to valvular heart disease, heart murmur, heart failure);
* History of skin allergy;
* Active skin disorder (e.g., psoriasis) within the last five years, except minor skin conditions (including but not limited to facial acne, minor localized infections, and superficial minor wounds);
* Liver or kidney disorder (except kidney stones, gallstones);
* Gastrointestinal problems or disease other than gastroesophageal reflux or heartburn;
* Active ulcers in the past 30 days;
* Currently symptomatic lung disorder/disease (including but not limited to chronic obstructive pulmonary disease (COPD), emphysema, and asthma);
* Brain abnormality (including but not limited to stroke, brain tumor, and seizure disorder);
* Migraine headaches that occur more frequently than once per week;
* Recent, unexplained fainting spells;
* Problems giving blood samples;
* Diabetes treated with insulin; non-insulin treated diabetes (unless glucose is less than 180mg/dcl and HbA1c is less than 7%);
* Current cancer or treatment for cancer in the past six months (except basal or squamous cell skin cancer);
* Other major medical condition;
* Current psychiatric disease (with the exception of anxiety disorders, obsessive compulsive disorder (OCD) and ADHD);
* Suicidal ideation (within the past 10 years) or lifetime occurrence of attempted suicide;
* Current depression;
* Bulimia or anorexia;
* Pregnant or nursing mothers;
* Alcohol abuse;
* Use of Opiate medications for pain or sleep in the past 14 days;
* Significant adverse reaction to nicotine patches, nicotine inhalers, bupropion / Wellbutrin / Zyban or Chantix / Varenicline in the past.
* Use (within the past 30 days) of:
* Illegal drugs (or if the urine drug screen is positive),
* Experimental (investigational) drugs;
* Psychiatric medications including antidepressants, anti-psychotics or any other medications that are known to affect smoking cessation (e.g. clonidine);
* Smokeless tobacco (chewing tobacco, snuff), cigars, pipes or e-cigarettes;
* Wellbutrin, bupropion, Zyban, Chantix, nicotine replacement therapy or any other smoking cessation aid.
C: Inclusion Criteria:

* Healthy male and female adolescents (12 - 16 years inclusive) with a total body weight greater than 30 kg who currently smoke an average of at least 3 cigarettes per day.

Exclusion Criteria:

* Male and female subjects with a positive urine drug screen and female subjects with a positive pregnancy test.
D: 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);

Answer: B