Please select the eligibility criteria that correspond to the clinical trial below.
Title: A 12-Week, Double-Blind, Placebo-Controlled, Multicenter Study With A 40 Week Follow Up Evaluating the Safety and Efficacy of Varenicline Tartrate 1 Milligram (Mg) Twice Daily (BID) for Smoking Cessation in Subjects With Cardiovascular Disease
Brief Summary: The primary purpose of this study is to determine whether or not varenicline will help people with cardiovascular disease quit smoking and to confirm it is safe in these patients.


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:

Participants will be required to satisfy all of the following criteria at the screening visit, unless otherwise stated:

• Participants will be: 1.1. over 23 years of age

• T2DM Patients will have: 2.1. body mass index (BMI) between 17.6 and 34.5 kg/m2, inclusive 2.2. body weight exceeding 50 kg (males) or 40 kg (females) 2.3 6.0\<HbA1C\<12 3.2. completion of proforma (CRF) 3.3. lab assessment as outlined in the CRF

* Participants will be willing to refrain from eating/drinking prior to screening and Check-in at each study visit.
* Participants will be regular smokers of at least 10 cigarettes/day (max 30 cigarette/day)
* Participants will have smoked for at least five consecutive years prior to screening.
* Participants must have a saliva cotinine level \> 10 ng/mL or an exhaled breath CO (eCO) level \> 7 ppm at screening.
* Participants in Arm A who continue to smoke will be willing to use their own brand/type cigarettes.
* Participants in Arms B will be willing to use the study products (THP product or e-cigarette) provided to them during the study.

Exclusion Criteria:

Participants will be excluded at the screening visit based on the following criteria:

* Female participants who are pregnant or breastfeeding. This will be confirmed at screening and at visit 1. Any female subject who becomes pregnant during this study will be withdrawn.
* Participants with a history of recent acute decompensation of their disease requiring treatment within 4 weeks prior to visit 1.
* Participants who have a significant history of alcoholism or drug/chemical abuse within 24 months prior to screening, as determined by the investigator.
* Participants who are still participating in another clinical study (e.g. attending follow-up visits) or who have participated in a clinical study involving administration of an investigational drug (new chemical entity) in the past 3 months prior to first product use.
* Participants who have, or who have a history of, any clinically-significant neurological, gastrointestinal, renal, hepatic, cardiovascular, psychiatric, respiratory, metabolic, endocrine, haematological or other major disorder that, in the opinion of the investigator or their appropriately qualified designee, would jeopardise the safety of the subject or impact on the validity of the study results.
* Participants who regularly use any nicotine (e.g. e-cigarettes, NRT) or tobacco product (e.g. HTPs, oral smokeless) other than their own cigarettes within 14 days of screening.

At screening and prior to enrolment, all patients will be offered a locally available free smoking cessation program as per local guidelines. Those who express the intention of booking for the cessation program together with those who, at screening, are planning to quit smoking in the next 6 months, will not be recruited in the study. Patients taking part in the study will be informed that they are free to quit smoking and withdraw from the study at any time. Any subject who decides to quit smoking will be directed to local stop smoking services.

Withdrawal Criteria:

Patients may be withdrawn from the study prematurely for the following reasons:

1. subject experiences a severe adverse event (SAE). The appropriate SAE electronic Case Report Form (eCRF) page must be completed.
2. If any deviations occur during the conduct of the study, which cannot be corrected. All protocol deviations will be fully documented and considered for their effect on study objectives. Deviations that could lead to subject discontinuation from the study include:

   * deviations which could affect subject's safety (e.g. illness requiring treatment\[s\]) which in the clinical judgement of the investigator might invalidate the study by interfering with the allocated test product or the willingness of the subject to comply with the study activities.
   * deviations involving the use of any nicotine/tobacco products other than the intended conventional cigarettes (in Arm A) or (in Arm B).
3. If the subject is uncooperative, including non-attendance. In these cases, efforts should have been made by the investigator to ascertain the reason and to ensure the subject's attendance as soon as possible.
4. Subject's personal request: the subject could decide, at any moment of the study, to stop his/her participation.
5. Female participant becoming pregnant.
C: Inclusion Criteria:

* Age 21-65
* Smoke \>9 cigarettes per day for at least 1 year
* Smoke regular filtered cigarettes or machine-rolled cigarettes with a filter
* CO measurement \>9 ppm at baseline
* No serious quit attempt in the prior 1 month. This includes use of any FDA approved smoking cessation medication (varenicline, bupropion \[used specifically as a quitting aid\], patch, gum, lozenge, inhaler, and nasal spray) in the past 1 month as an indication of treatment seeking.
* Not planning to quit in the next 6 months
* Interested in reducing cigarette consumption
* Willing to attend visits weekly and monthly over a 9-month period (not planning to move, not planning extended vacation, no planned surgeries)
* Read and write in English
* Able to understand and consent

Exclusion Criteria:

* Pregnant and/or nursing women
* Unstable or significant medical condition in the past 12 months (Recent heart attack or some other heart conditions, stroke, severe angina including high blood pressure if systolic \>159 or diastolic \>99 observed during screening).
* Immune system disorders, respiratory diseases (exacerbations of asthma or COPD, require oxygen, require oral prednisone), kidney (dialysis) or liver diseases (cirrhosis), or any medical disorder/medication that may affect participant safety or biomarker data.
* Use of any non-cigarette nicotine delivery product (pipe, cigar, dip, chew, snus, hookah, ECIGs, strips, sticks) in the past 7 days
* Uncontrolled mental illness or substance abuse or inpatient treatment for these in the past 6 months
* History of difficulty providing or unwilling to provide blood samples (fainting, poor veins, anxiety)
* No surgery requiring general anesthesia in the past 6 weeks
* Use of an ECIG for 5 or more days in the past 28 days or any use in the past 7 days
* Use of marijuana or any illicit drug/prescription drugs for non-medical use daily/almost daily, or weekly in the past 3 months per NIDA Quick Screen
* Use of hand-rolled, roll your own cigarettes
* Known allergy to propylene glycol or vegetable glycerin
* Other member of household is currently participating/participated in the study
D: Inclusion Criteria:

* smokers (at least 10 cigarettes/ day for the past year)
* willing to attempt quit smoking by using the National Health Service smoking cessation services or via e-cigarette use.

Exclusion Criteria:

* Non-ambulant people and people with a recent (e.g. within 6 months) cardiovascular disease event (e.g. stroke, myocardial infarction) or cardiac surgery,
* people with insulin-controlled diabetes mellitus or with coexisting skin conditions, leg ulcers, vasculitis or deep venous occlusion (as these may affect their cardiovascular function),
* pregnant women,
* people who require major surgery (which will prevent them of taking part in the study)
* people who following referral to the smoking cessation services, are advised that Nicotine Replacement Therapy is not appropriate for them,
* people who are currently using e-cigarettes on a daily basis, or currently undertaking an attempt within a smoking cessation service,
* people who are judged to be unable or are unwilling to give informed consent.

The study team will assess prospective participants and will not include in the study those who appear too frail or have health problems (e.g. dementia, Alzheimer's etc.) that might prevent them of giving a conscious, informed consent.

Answer: A