Please select the eligibility criteria that correspond to the clinical trial below.
Title: A 26-Week Phase II, Multicentre, Randomised, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Varenicline in Combination With Nicotine Replacement Therapy for Smoking Cessation
Brief Summary: The purpose of this study is to test whether the addition of a nicotine patch to varenicline increases smoking cessation success rate and whether the combination is safe.


Options:
A: Inclusion Criteria:

* History of alcohol dependence and at least one year of abstinence from alcohol intake.
* Has a history of smoking 20 or more cigarettes per day for the prior year.
* Can read and write English.
* Stated ability to fully participate in the study and keep all scheduled appointments.
* Has provided written informed consent.
* General good health.

Exclusion Criteria:

* Recent history (within three months) of a clinically significant myocardial infarction, unstable angina pectoris, serious cardiac arrhythmia or any other medical condition which the physician investigator deems incompatible with study participation.
* Current major depression. A past history of major depression will not be an exclusionary criteria.
* Current or previous use of bupropion (Wellbutrin).
* Active non- nicotine drug dependence.
* Past or current history of bipolar disorder, pain disorder or psychosis, schizophrenia, or other major psychiatric disorders.
* Current medically indicated use of psychiatric drugs.
* Females who are pregnant, lactating, or likely to become pregnant during the first year which includes the nicotine patch and bupropion (Wellbutrin) phase.
* History of severe skin allergies or evidence of severe chronic skin disorders.
* Current use of nicotine containing medication or tobacco products other than cigarettes.
* Current use (within 30 days of initiation of patch therapy) of the following medications for smoking cessation: clonidine, buspirone, or doxepin.
* A predisposition to seizures.
* A history of or current diagnosis of anorexia nervosa or bulimia.
* Medical disorder that would interfere with the absorption, metabolism, or excretion of bupropion (Wellbutrin).
B: A total of 120 subjects will be recruited in the study. Subjects will be eligible to participate if they:

1. Are at least 18 years of age;
2. Smoked more than10 cigarettes/day for the past one year;
3. Willing to make a quit attempt;
4. Able to participate fully in all aspects of the study; and
5. Have been provided with, understand, and have signed the informed consent.

Individuals will be excluded from study participation if they:

1. Meet diagnostic criteria for current major depressive disorder or lifetime history of bipolar disorder or schizophrenia. Patients with mild or moderate depressive symptoms \[Beck Depression Inventory, Second Edition \&#8804; 28\], but who do not meet current diagnostic criteria for major depressive disorder, will be included;
2. Are currently (within past 30 days) using antipsychotics or antidepressants;
3. Are currently (in previous 30 days) using any treatments for tobacco dependence (i.e., behavioral therapy, nicotine replacement therapy, bupropion SR, clonidine, or nortriptyline);
4. Have used an investigational drug within the 30 days prior to enrolling in this study;
5. Have ever used an herbal product for tobacco cessation;
6. Have recent history (in the past 3 months) of alcohol abuse or dependence as assessed by the CAGE questionnaire and study investigators;
7. Have a recent history of drug abuse as assessed by the Drug Abuse Screening Test 20 (DAST-20) and physician interview;
8. Are pregnant, lactating, or of child bearing potential, likely to become pregnant during the medication phase and not willing to use a reliable form of contraception. Reliable forms of contraception include barrier (diaphragm or condom with spermicidal jelly), injections, intrauterine device \[IUD\], surgical sterilization and abstinence;
9. Have a history of any major cardiovascular events in the past 6 months including unstable angina, acute MI or coronary angioplasty;
10. Have clinically significant acute or chronic progressive or unstable neurologic, hepatic, renal, cardiovascular, respiratory or metabolic disease;
11. Are currently on medications interacting with St. John?s Wort including warfarin, antiretrovirals (particularly indinavir and nevirapine), cyclosporine and tacrolimus, digoxin, nifedipine and verapamil, theophylline, all serotonergic drugs (serotonin reuptake inhibitors, tricyclic antidepressants, tramadol, venlafaxine, tryptophan and buspirone), MAO inhibitors, oral contraceptives, anti-cancer agents including imatinib and irinotecan, migraine medications (sumatriptan and zolmitriptan), methadone, lithium, sibutramine, atorvastatin and simvastatin, midazolam, alprazolam, fexofenadine, omeprazole, and general anesthetics (fentanyl, propofol, and sevoflurane);
12. Have another household member or relative participating in the study;
13. Have a known allergy to St. John?s Wort;
14. Have a history of photosensitivity;
15. Are professional drivers or operators of heavy machinery; and
16. Are scheduled for a planned surgical procedure within five days of taking SJW.
C: Inclusion Criteria:

* Long-term, daily NRT users (except nicotine patch) (\>11 months) ex-smokers that are willing to try to stop the use of NRT and adhere to this protocol.
* More than 4 pieces of nicotine gum/ sublingual tablets/ lozenges/ per day, OR more than 3 inhaler cylinders per day, OR
* more than 10 puffs of nasal spray per day.

Exclusion Criteria:

* Age \< 18 years,
* CO Smokers,
* Pregnant and lactating women,
* Used varenicline before,
* Not able to cooperate,
* Other significant diseases that might influence the trial (such as moderate -severe cardiac disease, lung cancer,) in expired air \> 7 ppm.
D: Inclusion Criteria:

1. Current cigarette smokers, male and female, aged between 18-75 years (both limits inclusive), and who are motivated to stop smoking.
2. Have smoked on average at least 10 cigarettes per day during past year and during the month prior to screening, and no period of abstinence greater than 3 months in the past year.
3. Women of child-bearing potential (WCBP) may be included provided they are not pregnant, not nursing, and meet all of the following criteria:

   * instructed and agree to avoid pregnancy through 30 days after the last dose of study medication
   * negative screening test (beta-HCG) at screening
   * agree to use at least one birth control method (oral contraceptive, IUD, implantable or injectable contraceptive for at least 1 month prior to entering the study and will continue its use through at least 30 days after the last dose of study medication, or use a barrier method of contraception (p.e.condom, diaphragm with spermicide) while participating in the study through at least 30 days after the last dose of study medication; or abstinence.
4. Patients must have no serious or unstable disease in the past 6 months.
5. Patients must be able to be outpatients, to be assessed in a clinical setting, and be able and willing to comply with all study visits during the treatment and non-treatment periods.
6. Only one subject per household may participate.

Exclusion Criteria:

1. Patients currently suffering from depression or who have been diagnosed with depression or treated with anti-depressants within the past 12 months.
2. Patients with a past of present history of psychosis, panic disorder, or bipolar disorder.
3. Patients with severe chronic obstructive pulmonary disease (COPD).
4. Patients with clinically significant cardiovascular disease in the past 6 months. such as myocardial infarction, coronary artery bypass graft (CABG), percutaneous transluminal coronary angioplasty (PTCA), severe or unstable angina, serious arrhythmia, and clinically significant ECG conduction abnormalities.
5. Patients with uncontrolled hypertension or a systolic blood pressure greater than 150mmHg or as diastolic pressure greater than 95mmHg at screening or baseline.
6. Patients with clinically significant neurological disorders or cerebrovascular diseases (for example, stroke, transient ischemic attack, etc.) in the past 6 months.
7. Patients with a history of clinically significant endocrine disorders or gastrointestinal diseases, including insulin dependent diabetes mellitus, uncontrolled hyperthyroidism, and active peptic ulcer.
8. Patients with clinically significant hepatic or renal impairment or other clinically significant abnormal laboratory test values.
9. Patients with a history of cancer (cured basal cell or squamous cell carcinoma of the skin allowed).
10. Patients with a history of clinically significant allergic reactions to drugs (for example, severe cutaneous and/or systemic allergic reactions).
11. Patients with a history of drug (except nicotine) or alcohol abuse or dependence within the past 12 months.
12. Patients with a body mass index (BMI) less than 15 or greater than 38 when wearing indoor clothing without shoes. No subject will be enrolled with a weight less than 45.5kg (100 pounds).
13. Patients previously enrolled in a study that included varenicline.
14. Patients having used nicotine replacement therapy within the last 6 months.
15. Patients taking another investigational drug within 30 days or 5 half-lives (whichever is longer) before the Baseline visit or within 30 days of study completion.
16. Use of prohibited medications: any antidepressants, including bupropion; antipsychotic agents; mood stabilizers; naltrexone; steroids (inhaled and topical steroids are permitted); insulin.
17. Patients who do not agree to completely abstain from using non-cigarette tobacco products (including for example, pipe tobacco, cigars, snuff, chewing tobacco, etc.) or marijuana during study participation.
18. Patients who intend to donate blood or blood components while receiving study drug or within 1 month of the completion of the study treatment.
19. Patients unable/or unlikely to comprehend and follow the study protocol, including patients unable and/or unwilling to participate in the non-treatment follow-up. Patients who, in the investigator's opinion, will be unlikely to commit to a 6 month-long study.
20. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study.

Answer: D