Impact of Very Low Nicotine Content Cigarettes in a Complex Marketplace

Study Overview
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Brief Summary
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This project will examine the impact of very low nicotine content (VLNC) cigarettes in a complex tobacco and nicotine product marketplace. We will compare the number of cigarettes smoked and cigarette-free days in an experimental marketplace that contains VLNC cigarettes versus normal nicotine content (NNC) cigarettes.

Detailed Description
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This randomized, open label, controlled, multi-site study will simulate a real world tobacco environment by providing participants access to an experimental marketplace where they will be given vouchers for a specified number of points that can be exchanged for study cigarettes (varying in nicotine content described below) and non-combusted tobacco/nicotine products (smokeless tobacco, snus, electronic cigarette, medicinal nicotine replacement) and at the end of the study can exchange unspent points for money. Subjects (N=200 in each group) will be randomly assigned to: 1) very low nicotine content cigarettes (VLNC; 0.4 mg/g) along with non-combusted tobacco/nicotine products or 2) normal nicotine content cigarettes (NNC; 15.8 mg/g) along with non-combusted tobacco/nicotine products. Smokers will undergo an orientation visit for screening and then enter a three phase experimental trial: Phase 1 - Baseline: Two week baseline assessment period during usual brand cigarette smoking. Phase 2 - Marketplace Adaptation: Two week period where subjects have access to the marketplace that provides their preferred usual brand cigarettes and selected non-combusted tobacco products to allow the subject to adjust to the marketplace prior to randomization; Phase 3 - Intervention: Randomization to a marketplace with access to either VLNC or NNC cigarettes plus non-combusted products for a 12 week period. Biomarker samples are collected at baseline, end of Phase 2 and end of week Phase 3 (week 12).

Official Title
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Impact of Very Low Nicotine Content Cigarettes in a Complex Marketplace Part of Evaluating New Nicotine Standards for Cigarettes

Conditions
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Tobacco Smoking, Nicotine Dependence

Intervention / Treatment
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* Drug: Very Low Nicotine Content Cigarettes
* Drug: Normal Nicotine Content Cigarettes


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female; At least 21 years of age; Biochemically confirmed smoker. Exclusion Criteria: Unstable health condition; Unstable medications; d) Pregnant or nursing.

Ages Eligible for Study
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Minimum Age: 21 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: Parallel Assignment
Interventional Model Description: Phase III randomized, open label, multi-center study that will examine the impact of very low nicotine content (VLNC) cigarettes using an experimental marketplace that contains tobacco and nicotine products, simulating a real world environment. There are three phases: Phase 1 is smoking usual brand cigarettes. Phase 2 is access to a marketplace with usual brand cigarettes and other non-combusted nicotine and tobacco products. Phase 3 involves access to a marketplace with study cigarettes and other non-combusted nicotine and tobacco products.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Very Low Nicotine Content Cigarettes<br>Very low nicotine content cigarettes (0.4 mg/g nicotine; 9 mg of tar) | Drug: Very Low Nicotine Content Cigarettes<br>* 0.4 mg/g nicotine; 9 mg tar<br>* Other names: Reduced Nicotine Content Cigarettes;|
| Active Comparator: Normal Nicotine Content Cigarettes<br>Normal (Conventional) Nicotine Content (15.8 mg/g nicotine; 9 mg of tar) | Drug: Normal Nicotine Content Cigarettes<br>* 15.8 mg/g nicotine; 9 mg tar<br>* Other names: Conventional Nicotine Content Cigarettes;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cigarettes Per Day (CPD) | The mean cigarettes (study and non-study cigarettes) smoked per day based on 7 days Daily Interactive Voice Response (IVR) data at the end of Phase 3 (experimental marketplace with study cigarettes) compared to Phase 2 (experimental marketplace with usual brand cigarettes). | 7 days prior to end of Phase 2 and the end of Week 12 (12 weeks on study cigarettes) | 
| Smoke-free Days | Rate of smoke-free days, defined as no cigarettes smoked in the past 24 hours calculated as the proportion of smoke-free days out of the total number of days in Phase 3. | 12 weeks on study cigarettes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change in 2-cyanoethyl-mercapturic Acid (CEMA) | Change in CEMA (biomarker for the mercapturic acid acrylonitrile) from end of Phase 2 (experimental marketplace with usual brand cigarettes) to end of Phase 3 (experimental marketplace with study cigarettes). | 12 weeks (Phase 3) on study cigarettes | 
| Study Cigarettes Per Day | The mean study cigarettes smoked per day based on 7 days Daily Interactive Voice Response (IVR) data at the end of Phase 3 (experimental marketplace with study cigarettes) compared to Phase 2 (experimental marketplace with usual brand cigarettes). | 12 weeks (Phase 3) on study cigarettes | 
| Seven-day Abstinence from Cigarettes | Total cigarettes per day equal to 0 for all 7 days before the week 12 visit and carbon monoxide (CO) ≤ 6ppm at week 12. | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Reduced nicotine cigarettes, Alternative nicotine products, Biomarkers of tobacco exposure