Combination Nicotine Patch / Lorcaserin for Smoking Cessation

Phase 2

Completed

Conditions: Nicotine Dependence

Interventions: Drug: lorcaserin
Drug: nicotine patch
Drug: placebo lorcaserin

Registration Number: NCT02906644

Lead Sponsor: Duke University

Brief Summary: This study plans to compare the efficacy of the nicotine patch / lorcaserin combination treatment vs. the nicotine patch alone in terms of leading to a reduction in smoking behavior and withdrawal symptoms.

Detailed Description: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 97

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lorcaserin + Patch	nicotine patch	Participants will receive lorcaserin (10mg twice a day) and nicotine patches (21mg/24hr) for 14 weeks, at which point the nicotine patch dosage will be reduced to 14mg/24hr for 1 week, followed by 7mg/24hr for 1 week.
Patch	placebo lorcaserin	Participants will receive nicotine patches (21mg/24hr) and placebo lorcaserin for 2 weeks; after 2 weeks participants will begin to receive active lorcaserin (10mg twice a day) along with the nicotine patches for 12 weeks, at which point the nicotine patch dosage will be reduced to 14mg/24hr for 1 week, followed by 7mg/24hr for 1 week.
Patch	nicotine patch	Participants will receive nicotine patches (21mg/24hr) and placebo lorcaserin for 2 weeks; after 2 weeks participants will begin to receive active lorcaserin (10mg twice a day) along with the nicotine patches for 12 weeks, at which point the nicotine patch dosage will be reduced to 14mg/24hr for 1 week, followed by 7mg/24hr for 1 week.
Lorcaserin + Patch	lorcaserin	Participants will receive lorcaserin (10mg twice a day) and nicotine patches (21mg/24hr) for 14 weeks, at which point the nicotine patch dosage will be reduced to 14mg/24hr for 1 week, followed by 7mg/24hr for 1 week.
Patch	lorcaserin	Participants will receive nicotine patches (21mg/24hr) and placebo lorcaserin for 2 weeks; after 2 weeks participants will begin to receive active lorcaserin (10mg twice a day) along with the nicotine patches for 12 weeks, at which point the nicotine patch dosage will be reduced to 14mg/24hr for 1 week, followed by 7mg/24hr for 1 week.

Primary Outcome Measures

Name	Time	Method
Smoking Withdrawal	Week 2 pre quit day	At the study visit above (two week post treatment initiation but 2 weeks prior to quit day), withdrawal symptoms will be assessed after 2 hours of smoking abstinence using the Shiffman-Jarvik (short form) questionnaire, which consists of 9 items rated from 1 to 7, where 1= not at all, 2= very little, 3= a little, 4= moderately, 5= a lot, 6= quite a lot, and 7= extremely. The 9 items are grouped into 8 subscales: Craving, Negative Affect, Appetite, and Arousal. The range of scores for each subscale will be 1-7, with higher scores indicating more of the withdrawal symptom having been experienced.
Time-to-lapse	Week 2 pre quit day	Two weeks after treatment is initiated, with nicotine patch + lorcaserin or nicotine patch alone, but still two weeks prior to the quit day, subjects will be evaluated in a modified version of the McKee Smoking Lapse Task. In this task smokers, who have been abstinent for 2 hours will be provided with the option to smoke at any time, but paid by the minute for remaining abstinent with progressively decreasing payments over an hour.

Secondary Outcome Measures

Name	Time	Method
Adherence to Lorcaserin + Nicotine Patch Treatment as Indicator of Tolerability	Two Weeks pre and 10 weeks post quit day	Tolerability of the lorcaserin + nicotine patch treatment will be assessed by calculating adherence scores based on the percentage of days on which the study drugs were taken between visits as reported by participants on diaries.
Number of Participants Reporting Smoking Abstinence	Weeks 7-10 post quit day	Number of participants who reported continuous four-week abstinence from smoking (weeks 7-10 post target quit date), confirmed by expired air carbon monoxide (CO).
Number of Participants Reporting Tolerability Issues With Lorcaserin + Nicotine Patch Treatment	Two Weeks pre and 10 weeks post quit day	Tolerability of the lorcaserin + nicotine patch treatment will be assessed by tabulating the number of participants rating side effects \> "moderate".
Weight Gain Following Continuous Four-week Abstinence From Smoking	Week 10 post quit day	Among smoking-abstinent participants, weight gain relative to baseline will be assessed.
Number of Participants Reporting 6-month Smoking Abstinence	6 months post Quit Day	Number of participants who reported not smoking for the previous seven days when called for 6-month follow-up, confirmed by expired air carbon monoxide (CO).
Percentage of Change in Ad Libitum Smoking at End of Week 2	Week 2 pre quit day	To evaluate the effects of lorcaserin on ad libitum (ad lib) smoking, the percent change in reported number of cigarettes smoked from baseline to the end of week 2 (the day prior to the 2nd study visit) will be calculated.