Pharmacokinetics, Subjective Effects, and Abuse Liability of Nicotine Salt-Based Vaping Products With Tobacco or Unflavored E-liquids, SALTVAPE Study

Study Overview
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Brief Summary
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This trial studies activity of time (pharmacokinetics), subjective effects, and abuse liability of nicotine salt-based vaping products with tobacco or e-liquids. This study aims to determine and compare the levels of nicotine delivered to the bloodstream from nicotine salt and free-base nicotine e-liquid solutions.

Detailed Description
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PRIMARY OBJECTIVES: I. To determine the effect of nicotine salt (nicotine benzoate) and free-base nicotine in different flavored e-liquid solutions on puffing behaviors and systemic exposure to nicotine from electronic nicotine delivery systems (ENDS) by: Ia. Assessing short-term effects on nicotine cravings, withdrawal, and satisfaction from single use of ENDS refilled with flavored nicotine salt or flavored free-base nicotine solutions with two different flavors (tobacco or unflavored) in current daily ENDS users following an overnight fast. Ib. Comparing users' perceptions and preferences towards inhaling vapors containing nicotine salt (nicotine benzoate) or freebase nicotine with two different flavors (tobacco and unflavored) versus their regular brand. II. This project provides important information on whether the pharmacokinetics of nicotine delivery differ between salt and free-base forms of e-liquid of equivalent nominal concentration using the same device, and whether the previously observed effects of flavors on subjective effects differ between salt and free-base forms. III. Determine whether maximum concentration of nicotine in plasma (Cmax) or time to maximum concentration (Tmax) differ between free-base and salt-based versions of the same liquid, controlling for flavoring and nominal nicotine concentration [main effect of salt]. IV. Determine whether the effect of flavoring on subjective effects (e.g., harshness, liking) differs between matched free-base and salt-based e-liquids [flavor X salt interaction]. EXPLORATORY OBJECTIVE: I. Examine effects of salt and flavoring on abuse liability using the Experimental Tobacco Marketplace (ETM). OUTLINE: After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours, 5-7 days apart. During each session, participants take 20 puffs over 10 minutes (one puff every 30 seconds) of vaporizer filled with freebased nicotine electronic (e)-liquid solution of unflavored, free-based nicotine e-liquid solution of tobacco flavor, salt-based nicotine e-liquid solution of unflavored, or salt-based nicotine e-liquid solution of tobacco flavor assigned in a random order.

Official Title
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Pharmacokinetics, Subjective Effects, and Abuse Liability of Nicotine Salt-Based Vaping Products With Tobacco or Unflavored E-liquids[SALTVAPE Study]

Conditions
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Nicotine Dependence

Intervention / Treatment
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* Drug: Nicotine
* Device: Vaporizer Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willingness to abstain from using ENDS product for 8-10 hours (overnight abstinence) prior to study visits Current daily ENDS user as determined by Has used ENDS product every day for the past 6 months (by history) Has used ENDS product or e-liquid containing nicotine (by history) Participant or legal representative must understand the investigational nature of this study and sign and Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure Exclusion Criteria: Smoked cigarettes in the past 7 days Currently smokes >= 5 cigarettes per month Unstable medical conditions (such as unstable heart disease, uncontrolled hypertension, thyroid disease, diabetes, renal or liver impairment, or glaucoma) or psychiatric condition (such as current major depression, history of schizophrenia or bipolar disorder) or current regular use of psychiatric medications (such as major tranquilizers and antidepressants) History of serious side effects from nicotine or from any nicotine replacement therapies Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant or nursing females Concurrent participation in another clinical trial Unwilling or unable to follow protocol requirements Any condition which in the investigator's opinion deems the participant an unsuitable candidate

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 55 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: Prevention
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: The participant and researcher will be blinded to solution flavor and nicotine consentration.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low Nicotine (nicotine vapor) 24 mg.ml<br>After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours, 5-7 days apart. During each session, participants take 20 puffs over 10 minutes (one puff every 30 seconds) of vaporizer filled with freebased nicotine e-liquid solution of unflavored, free-based nicotine e-liquid solution of tobacco flavor, salt-based nicotine e-liquid solution of unflavored, or salt-based nicotine e-liquid solution of tobacco flavor assigned in a random order. | Drug: Nicotine<br>* Vape different flavor nicotine products<br>* Other names: NIC;Device: Vaporizer Device<br>* Take puffs from vaporizer filled with different flavors<br>* Other names: Vaporizer;|
| Experimental: High Nicotine (nicotine vapor) 42 mg.ml<br>After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours, 5-7 days apart. During each session, participants take 20 puffs over 10 minutes (one puff every 30 seconds) of vaporizer filled with freebased nicotine e-liquid solution of unflavored, free-based nicotine e-liquid solution of tobacco flavor, salt-based nicotine e-liquid solution of unflavored, or salt-based nicotine e-liquid solution of tobacco flavor assigned in a random order. | Drug: Nicotine<br>* Vape different flavor nicotine products<br>* Other names: NIC;Device: Vaporizer Device<br>* Take puffs from vaporizer filled with different flavors<br>* Other names: Vaporizer;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum concentration of nicotine in plasma (Cmax) | Each outcome will be modeled as a function of base (free-base versus salt based), flavor (tobacco versus unflavored), their interaction, prior combination indicator (for carry over effect), and a random subject effect using a linear mixed model. All model assumptions will be verified graphically and transformations will be applied as appropriate. The effect of base on the Cmax will be evaluated using tests about the least square means of base. Additionally, 95% confidence intervals about the mean differences will be obtained. | Up to 1 year | 
| Area under the concentration-time curve (AUC) | Each outcome will be modeled as a function of base (free-base versus salt based), flavor (tobacco versus unflavored), their interaction, prior combination indicator (for carry over effect), and a random subject effect using a linear mixed model. All model assumptions will be verified graphically and transformations will be applied as appropriate. The effect of base on the AUC nicotine will be evaluated using tests about the least square means of base. Additionally, 95% confidence intervals about the mean differences will be obtained. | From 0 to 120 minutes | 
| Time to maximum concentration | Each outcome will be modeled as a function of base (free-base versus salt based), flavor (tobacco versus unflavored), their interaction, prior combination indicator (for carry over effect), and a random subject effect using a linear mixed model. All model assumptions will be verified graphically and transformations will be applied as appropriate. The effect of base on the Tmax measures will be evaluated using tests about the least square means of base. Additionally, 95% confidence intervals about the mean differences will be obtained. | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjective measure of perceived harshness of nicotine withdrawal symptoms | A Sensory Measuring scale will be used with -100 least intense and 100 most intense. | Up to 1 year | 
| Subjective measure of perceived satisfaction of nicotine withdrawal symptoms | Product evaluation scale with 4 being most satisfying and 1 being least satisfying | Up to 1 year | 
| Subjective measure of perceived liking of nicotine withdrawal symptoms | Product evaluation scale with 4 being most satisfying and 1 being least satisfying | Up to 1 year | 
| Change in nicotine withdrawal symptoms | Minnesota Nicotine Withdrawal Scale | Up to 1 year |