Test of Novel Drug for Smoking Cessation

Study Overview
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Brief Summary
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The study will assess a novel active drug vs. placebo on ability to reduce smoking and aid cessation during a one-week practice quit period for each condition in smokers with a high interest in quitting (i.e. crossover design). Medication effects on reducing withdrawal and cognitive impairment will help assess the mechanism to support quit smoking attempts.

Detailed Description
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We aim to test the proof of principal that an alpha-7 PAM drug, JNJ-39393406, promotes smoking cessation when compared to placebo. We have developed, tested, and validated an efficient Phase 2a screening procedure that optimally combines the validity of randomized clinical trials with the practicality of lab- based medication studies. Notably, it employs a within-subject, cross-over design comparing active versus placebo effects on quitting smoking to maximize statistical power without a large sample, in contrast to the large samples needed for between-groups randomized treatment conditions. Using this procedure, we will evaluate effects of JNJ-39393406 vs. placebo on short-term smoking abstinence in smokers who already have a high interest in quitting soon. We predict that, compared with placebo, JNJ-39393406 will increase days of abstinence, identifying initial evidence of efficacy for smoking cessation. Our main dependent measure is days of very stringent biochemically validated (expired CO<5 ppm) 24-hr smoking abstinence, with post-quit withdrawal and cognitive function as secondary measures. Potential for adverse side-effects will be assessed at each visit.

Official Title
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Development of a Novel Therapeutic for Smoking Cessation

Conditions
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Smoking Cessation

Intervention / Treatment
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* Drug: Active JNJ Drug
* Drug: Placebo pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female dependent smokers wanting to quit soon - Exclusion Criteria: Use of non-smoked nicotine products Already enrolled in cessation program. Recent alcohol or substance dependence (≤ 3 months) Women who are pregnant, planning a pregnancy, or lactating; all female participants shall undergo a pregnancy test at screening and will be excluded if positive. Serious or unstable medical disorder within the past 3 months Epilepsy Current diagnosis (within last 6-months) of abnormal cardiac rhythms; unstable cardiovascular disease e.g. stroke, myocardial infarction in the last 6 months Evidence impaired liver function test (LFT) Evidence of kidney failure Any subject with a history of hematological cancers examples: leukemia, lymphoma etc. Any clinically significant hematological laboratory abnormality.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Crossover of active JNJ vs. placebo for 2 weeks each, involving 1 week of dose run-up and 1 week of attempting to quit each day on that drug condition. A one-week washout separates these drug conditions, which are administered in counter-balanced order.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JNJ Active Drug<br>200 mg (100 mg b.i.d.) Active JNJ Drug used to assess quitting for one week, as part of crossover design. This JNJ experimental compound has NO name, just a company number. | Drug: Active JNJ Drug<br>* 200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week.<br>* Other names: JNJ-39393406;Drug: Placebo pill<br>* Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week.<br>|
| Experimental: Placebo Pill<br>Placebo pill used for one week quit attempt, as part of crossover design. | Drug: Active JNJ Drug<br>* 200 mg/day (100 mg b.i.d.) of Active JNJ Drug will be used for one week while attempting to briefly quit smoking on Mon-Fri of that week.<br>* Other names: JNJ-39393406;Drug: Placebo pill<br>* Placebo pill will be taken daily to assess ability to briefly quit smoking on Mon-Fri for one week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quit Status | Complete abstinence from smoking for 24 hr is counted as a quit day and is assessed daily from Mon-Fri for just one week, on the JNJ active drug and one week on placebo. This same Mon-Fri procedure for one week (only) is done for both drug phases. Total outcome in each drug condition therefore is number of quit days out of the five assessment days (range 0-5). | up to one week each drug phase (0-5) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minnesota Nicotine Withdrawal Scale (MNWS) During Attempt to Quit on Active JNJ Drug and on Placebo | Severity of withdrawal symptoms will be assessed with standard self-report measure of Minnesota Nicotine Withdrawal Scale (MNWS) each quit day during one week only on active JNJ, and each quit day during one week on placebo. Ratings are made on 0-100 visual analog scale, with 0=not at all to 100=very much, and are averaged to create a total score also ranging from 0-100. Higher scores indicate more severe withdrawal. | only on days quit while on JNJ or on placebo | 
| Cognitive Function on Continuous Performance Task (CPT) for Those With CO<10 During First Assessment Day (Mon) of Attempt to Quit Smoking During Both JNJ and Plac Quit Periods | This measure of cognitive performance (mean of median speed of correct responding on computer keyboard to letters and numbers) was assessed only on Monday (day 1) of the 0-5 days during each drug/placebo condition. Data only from those shown to have CO<10 ppm were analyzed, to confirm responding during abstinence while on drug/placebo condition. Cognitive testing consisted of standard Continuous Performance Task (CPT), on active JNJ and on placebo phases. This measure is assessed to determine potential mechanism of drug efficacy in relieving disrupted cognitive processing function caused by tobacco deprivation and withdrawal. | first day during quit week on JNJ, and during quit week on placebo. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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crossover