Combination Nicotine Patch / Lorcaserin for Smoking Cessation

This study proposes to investigate the potential efficacy of a combination of two
FDA-approved agents, nicotine patch and lorcaserin, for smoking cessation treatment. The
nicotine patch which provides a sustained low dose of nicotine is a nicotine receptor
agonist. Lorcaserin, a serotonin 5-hydroxytryptamine receptor 2C (5-HT2C) agonist, is a drug
that is FDA-approved for weight loss, and has also recently been shown to be efficacious for
smoking cessation. Given that these drugs act through distinct mechanisms it is hoped that
the combination will prove more efficacious than either drug alone. It is also hypothesized
that the combination will reduce weight gain commonly seen after smoking cessation.

Inclusion Criteria:

- 18-65 years old;

- Smoke an average of at least 10 cigarettes per day;

- Have smoked at least one cumulative year;

- Have an expired air CO reading of at least 10ppm;

- Body weight of >50 kg (110 lbs.)

- Able to read and understand English;

- Express a desire to quit smoking in the next thirty 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).

- Participants with a history of hypertension may, however, be allowed to participate in
the study if the study physician or physician assistant determines that the condition
is stable, controlled by medication, and in no way jeopardizes the individual's
safety.

- Coronary heart disease, diagnosed by coronary angiogram;

- Lifetime history of heart attack;

- Cardiac rhythm disorder (irregular heart rhythm);

- Chest pain in the last month (unless history, exam, and ECG clearly indicate a
non-cardiac source);

- Symptomatic cardiac (heart) disorder (including but not limited to valvular heart
disease, heart murmur, heart failure);

- Diagnosis of liver disease or kidney disorder (except kidney stones, gallstones);

- Gastrointestinal problems (e.g. Celiac disease, Crohn's dx Ulcerative Colitis) 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 (unless controlled by diet and exercise alone and screening 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);

- HIV, Hepatitis B, or Hepatitis C

- History of tuberculosis or recent positive purified protein derivative (PPD) test

- Other major medical condition;

- Current psychiatric disease (with the exception of anxiety disorders, obsessive
compulsive disorder (OCD) and ADHD);

- Suicidal ideating (thinking about ways to commit suicide) (within the past 10 years)
or lifetime occurrence of attempted suicide;

- Current depression - The Patient Health Questionnaire (PHQ-9) for Depression will be
used to screen for current (within 2 weeks) depression. Potential subjects who score
>9 (or who score >0 on item #9 ("Thoughts that you would be better off dead, or of
hurting yourself in some way") will be excluded from study participation, and, at the
discretion of the study physician, referred to appropriate psychiatric treatment;

- Bulimia or anorexia;

- BMI of < 18.5 kg/m2;

- Prior use of fenfluramine or dexfenfluramine

- Use (within the past 30 days) of:

- Illegal drugs (or if the urine drug screen is positive for tetrahydrocannabinol
(THC), Cocaine, Amphetamine, Opiates, Methamphetamines, phencyclidine (PCP),
Benzodiazepines, or Barbiturates), Unless recent use of prescription Opiates,
Benzodiazepines for management of acute symptoms.

- Experimental (investigational) drugs;

- Psychiatric medications including antidepressants (selective serotonin reuptake
inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs),
tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), St.
John's Wort), lithium, anti-psychotics or any other medications that are known to
affect smoking cessation (e.g. clonidine);

- Phentermine, triptans, tryptophan, linezolid, dextromethorphan, opiates,
tramadol, or dopamine agonists;

- Any agents that have documented correlation with increased incidence of
valvulopathy and/or pulmonary hypertension (e.g., cyproheptadine, trazodone,
nefazodone, amoxapine, tricyclic antidepressants, mirtazapine, pergolide,
ergotamine, methysergide) (or anticipated use during the study);

- Smokeless tobacco (chewing tobacco, snuff), pipes or e-cigarettes;

- Wellbutrin, bupropion, Zyban, Chantix, varenicline, nicotine patch, nicotine
replacement therapy or any other smoking cessation aid.

- Concurrent use of a serotonergic agent/combination associated with severe serotonin
syndrome (within the past 30 days);

- Use of cigar, cigarillos, pipe, Hookah, dissolvable nicotine, snuff, chewing tobacco
more than once per month.

- Use of e-cigarettes once per month or more.

- Self-report of consuming 4 or more alcoholic drinks on 1 or more days per week;

- Significant adverse reaction to lorcaserin or nicotine patch in the past.

- Current participation or recent participation (in the past 30 days) in another smoking
study at the investigators Center or another research facility.

- Current participation in another research study.