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:

* Male or female cigarette smokers, 18-75 years, motivated to stop smoking and considered suitable for a smoking cessation attempt
* Smoked an average of at least 10 cigarettes per day during past year and over past month, and exhaled carbon monoxide (CO) \> 10 ppm at screening
* Current or past diagnosis of MDD without psychotic features, either single or recurrent, using DSM IV TR based on clinical assessment and confirmed by SCID and at least one of the following:
* On stable antidepressant treatment for MDD (stable dose for at least 2 months)
* Major depressive episode, using DSM IV TR, in the past 2 years successfully treated

Exclusion Criteria:

* Current or past diagnosis of dementia, schizophrenia, schizoaffective disorder, or other psychotic disorder, bipolar I disorder, bipolar II disorder.
* Subjects with antisocial, schizotypal, or any other personality disorder severe enough to compromise the subject's ability to comply with the study requirements..
* Current use of either bupropion or nortryptiline.
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. 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.
D: Subject inclusion criteria

1. DSM IV-TR Bipolar I or II or Bipolar NOS Disorder
2. Ability to provide written informed consent
3. Male or Female patients, all races, ages 18 to 65 years inclusive
4. Negative serum pregnancy test for females of child-bearing potential. Patients must agree to one of the following birth control methods: an oral contraceptive agent, an intrauterine device (IUD), an implantable contraceptive (e.g., Norplant), or an injectable contraceptive (e.g., Depo Provera) 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 a barrier method of contraception, e.g., condom and/or diaphragm with spermicide while participating in the study through at least 30 days after the last dose of study medication or abstinence.
5. MADRS total scores ≤ 8 (past 4 weeks) (suicidal item, score ≤ 1, past 4 weeks).
6. Y-MRS scores ≤ 8 (past 4 weeks) irritability, speech content, disruptive, or aggressive behavior items score ≤ 3, past 4 weeks)
7. Stable doses of primary bipolar maintenance medication for at least 8 weeks prior to randomization
8. No psychiatric hospitalization or Emergency Room Visits for psychiatric issues in the 6-month period prior to randomization
9. No suicidal attempts or behavior history past 6 months
10. No aggressive or violent acts or behavior by history past 6 months

Subject exclusion criteria

1. Uncontrolled seizure disorders and other neurological disorders including Huntington's Chorea, Multiple Sclerosis, Cerebral Palsy, and stroke (cerebrovascular accident, CVA).
2. Current alcohol or other substance abuse or dependence within the last 3 months (caffeine will be permitted, nicotine dependence is part of inclusion criteria), including a case-by-case evaluation of those who meet remission criteria and who are on long-term substance abuse and/or alcohol abuse treatment.
3. Female patients who are pregnant, lactating or likely to become pregnant in next 6 months
4. Uncontrolled diabetes mellitus, asthma, seizure disorder, uncontrolled hypertension, (uncontrolled hypertension is defined as Systolic BP \> 150 mm or Hg or diastolic BP \> 95 mm or Hg on 2 consecutive BP readings 15 minutes apart at the time of screening) or unstable medical illness. Moderate to severe renal disease - moderate renal failure is defined as serum Creatinine \>1.3 mg/dl in women and \> 1.5 mg/dl in men, at the time of screening.
5. Severe dizziness or fainting due to orthostatic blood pressure changes
6. Known hypersensitivity to varenicline
7. Current use of cimetidine
8. Current treatment with heparin, warfarin, or lidocaine
9. Comorbid psychiatric condition diagnosed within the last three months.

Subject smoking inclusion criteria

1. Score of 7 or greater on the Contemplation Ladder, and willing to pick a target quit date within the next 4 weeks.
2. Smoke \> 10 cigarettes per day.
3. Expired breath CO level \> 10 ppm at screening and randomization.
4. No use of smoking cessation medication and/or behavioral treatment for smoking cessation in the past three months.
5. No current use of any nicotine replacement treatment.
6. Not using any tobacco products other than cigarettes.
7. No current treatment for smoking cessation (hypnosis, acupuncture, others).
8. No current use or past treatment failure with varenicline.
9. No current treatment with bupropion for smoking cessation.

Answer: C