Nicotine Dependence
Conditions
Brief summary
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
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.
Interventions
DRUGNicotine
Vape Free-Low nicotine unflavored
DEVICEVaporizer Device
Take puffs from vaporizer filled with different flavors
DRUGSalt-HIgh Nicotine Unflavored (Product B)
Vape Salt-High nicotine unflavored
DRUGFree-Low Nicotine Tobacco Flavored (Product C)
Vape Free-Low Nicotine Tobacco
DRUGSalt-High Nicotine Tobacco Flavored (Product D)
Vape Salt-High Tobacco
Sponsors
National Cancer Institute (NCI)
Roswell Park Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Intervention model description
The participant and researcher will be blinded to solution flavor and nicotine concentrates.
Eligibility
Sex/Gender
ALL
Age
21 Years to 55 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-time Curve (AUC) | Samples were taken at minutes 0, then they started puffing and samples were taken 2, 4, 5, 6, 8, 10 minutes during puffing. Then, samples were taken at times 13, 15, 20, 30, and 120 minutes post puffing. The last dose occurred at week 4. | Area under the plasma nicotine concentration over time curve |
| Maximum Concentration of Nicotine in Plasma (Cmax) | Samples were taken at minutes 0, then they started puffing and samples were taken 2, 4, 5, 6, 8, 10 minutes during puffing. Then, samples were taken at times 13, 15, 20, 30, and 120 minutes post puffing. The last dose occurred at week 4. | The maximum nicotine concentration in blood plasma |
| Time to Maximum Concentration | Samples were taken at minutes 0, then they started puffing and samples were taken 2, 4, 5, 6, 8, 10 minutes during puffing. Then, samples were taken at times 13, 15, 20, 30, and 120 minutes post puffing. The last dose occurred at week 4. | Time to maximum nicotine concentration in the blood plasma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Minnesota Nicotine Withdrawal Scale Change (Change From Pre- to Post-) | 5 minutes pre puffing and 3 minutes post puffing for 4 weeks | Minnesota Nicotine Withdrawal Scale Change Minnesota Nicotine Withdrawal scale measures 8 facets of withdrawal and results in a total score. We use change from 5 minutes Pre-puffing to 3 minutes post puffing session. Individual questions are scored 0 (none/better) to 4 (severe/worse). And then the scores are totaled. Positive change score = more withdrawal symptoms. Change score can range from -32 to 36). Positive change score = worse withdrawal symptoms Individual questions are scored 0 (none/better) to 4 (severe/worse). And then the scores are totaled. |
| Perceived Liking of Experimental Product Sampled | 1 minute post puffing for 4 weeks | Drug Effects Questionnaire Item #1 - perceived liking of the experimental product assessed by the question, Do you like any of the effects you are feeling right now? on a Likert scale from 0 (not at all) to 100 (extremely), with lower scores representing less liking of the experimental product. Mean is provided with possible scores between 0 and 100. |
| Perceived Harshness of Experimental Product Sampled | 1 minute post puffing for 4 weeks | Subjective Measure of Perceived Harshness (Likert, 1-5: 1 = best outcome, 5 = worst outcome). |
| Perceived Satisfaction of Experimental Product Sampled | 120 minutes after session start on last session (session 4) | Nicotine Solution Rating Scale that orders each of the four products from 1 to 4, with 1 being least satisfying and 4 being most satisfying. Mean rank is provided with a possible score of 1 through 4. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Intensity of Demand or Estimated Milligrams E-cigarettes Purchased at Free Cost for Each Device Sampled | 60 minutes post puffing for 4 weeks | Demand intensity is a behavioral economic estimated measure of consumption at zero cost in a experimental marketplace focused on purchasing of tobacco and nicotine products over increasing price of one product while others stay the same price. Participants were asked to purchase tobacco products (12 options) for one week's use. At each of the four sessions, participants experienced a marketplace with e-cigarette liquid prices of $1.63, $3.25, $6.50, and $13.00, while the prices of the other 11 tobacco products remained the same. Units purchased are transformed into mg of nicotine and nonlinear regression is used to estimate the purchasing when e-cigarettes are free/demand intensity, which is reported here. Higher scores indicate more mg of nicotine from e-cigarettes were purchased |
| Substitution Levels of Alternative Tobacco Products | 120 minutes post puffing for 4 weeks | Substitution is the slope of the line regressing consumption of the substitute product onto the price of cigarettes (cross-price elasticity). A positive coefficient indicates substitution (use of the substitute increases with increasing cigarette price). A negative value indicates complementarity (use of the substitute declines with increasing cigarette price). A value of 0 indicates no relationship. |
| Elasticity of Demand or Sensitivity to Price for Each Device Sampled | 60 minutes post puffing for 4 weeks | Demand elasticity , or sensitivity to price, is a behavioral economic measure of of the rate of purchasing decline over increasing cost for e-cigarettes. At each of the four sessions, participants experienced a marketplace with e-cigarette liquid prices of $1.63, $3.25, $6.50, and $13.00, while the prices of the other 11 tobacco products remained the same. Units purchased are transformed into mg of nicotine and nonlinear regression is used to estimate the purchasing when e-cigarettes are free/demand intensity, which is reported here. Higher scores indicate more sensitivity to price, also called inelastic demand. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Product Sequence D After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with one of the following: 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 random order.
Vaporizer Device: Take puffs from vaporizer filled with different flavors
Salt-High Nicotine Tobacco Flavored (Product D): Vape Salt-High Tobacco | 2 |
| Product Sequence A Then B Then C After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with one of the following: 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 random order.
Nicotine: Vape Free-Low nicotine unflavored
Vaporizer Device: Take puffs from vaporizer filled with different flavors
Salt-HIgh Nicotine Unflavored (Product B): Vape Salt-High nicotine unflavored
Free-Low Nicotine Tobacco Flavored (Product C): Vape Free-Low Nicotine Tobacco | 1 |
| Product Sequence B Then C Then A Then D After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with one of the following: 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 random order.
Vaporizer Device: Take puffs from vaporizer filled with different flavors
Salt-HIgh Nicotine Unflavored (Product B): Vape Salt-High nicotine unflavored
Free-Low Nicotine Tobacco Flavored (Product C): Vape Free-Low Nicotine Tobacco
Salt-High Nicotine Tobacco Flavored (Product D): Vape Salt-High Tobacco | 1 |
| Product Sequence D Then B Then A Then C After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with one of the following: 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 random order.
Nicotine: Vape Free-Low nicotine unflavored
Vaporizer Device: Take puffs from vaporizer filled with different flavors
Salt-HIgh Nicotine Unflavored (Product B): Vape Salt-High nicotine unflavored
Free-Low Nicotine Tobacco Flavored (Product C): Vape Free-Low Nicotine Tobacco
Salt-High Nicotine Tobacco Flavored (Product D): Vape Salt-High Tobacco | 1 |
| Product Sequence C Then D Then B Then A After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with one of the following: 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 random order.
Nicotine: Vape Free-Low nicotine unflavored
Vaporizer Device: Take puffs from vaporizer filled with different flavors
Salt-HIgh Nicotine Unflavored (Product B): Vape Salt-High nicotine unflavored
Free-Low Nicotine Tobacco Flavored (Product C): Vape Free-Low Nicotine Tobacco
Salt-High Nicotine Tobacco Flavored (Product D): Vape Salt-High Tobacco | 1 |
| Product Sequence A Then C After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with one of the following: 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 random order.
Nicotine: Vape Free-Low nicotine unflavored
Vaporizer Device: Take puffs from vaporizer filled with different flavors
Free-Low Nicotine Tobacco Flavored (Product C): Vape Free-Low Nicotine Tobacco | 1 |
| Product Sequence D Then C Then B Then A After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with one of the following: 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 random order.
Nicotine: Vape Free-Low nicotine unflavored
Vaporizer Device: Take puffs from vaporizer filled with different flavors
Salt-HIgh Nicotine Unflavored (Product B): Vape Salt-High nicotine unflavored
Free-Low Nicotine Tobacco Flavored (Product C): Vape Free-Low Nicotine Tobacco
Salt-High Nicotine Tobacco Flavored (Product D): Vape Salt-High Tobacco | 1 |
| Product Sequence A Then D Then B Then C After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with one of the following: 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 random order.
Nicotine: Vape Free-Low nicotine unflavored
Vaporizer Device: Take puffs from vaporizer filled with different flavors
Salt-HIgh Nicotine Unflavored (Product B): Vape Salt-High nicotine unflavored
Free-Low Nicotine Tobacco Flavored (Product C): Vape Free-Low Nicotine Tobacco
Salt-High Nicotine Tobacco Flavored (Product D): Vape Salt-High Tobacco | 1 |
| Product Sequence D Then A Then C Then B After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with one of the following: 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 random order.
Nicotine: Vape Free-Low nicotine unflavored
Vaporizer Device: Take puffs from vaporizer filled with different flavors
Salt-HIgh Nicotine Unflavored (Product B): Vape Salt-High nicotine unflavored
Free-Low Nicotine Tobacco Flavored (Product C): Vape Free-Low Nicotine Tobacco
Salt-High Nicotine Tobacco Flavored (Product D): Vape Salt-High Tobacco | 1 |
| Product Sequence C Then D Then A Then B After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with one of the following: 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 random order.
Nicotine: Vape Free-Low nicotine unflavored
Vaporizer Device: Take puffs from vaporizer filled with different flavors
Salt-HIgh Nicotine Unflavored (Product B): Vape Salt-High nicotine unflavored
Free-Low Nicotine Tobacco Flavored (Product C): Vape Free-Low Nicotine Tobacco
Salt-High Nicotine Tobacco Flavored (Product D): Vape Salt-High Tobacco | 1 |
| Product Sequence A Then C Then D Then B After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with one of the following: 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 random order.
Nicotine: Vape Free-Low nicotine unflavored
Vaporizer Device: Take puffs from vaporizer filled with different flavors
Salt-HIgh Nicotine Unflavored (Product B): Vape Salt-High nicotine unflavored
Free-Low Nicotine Tobacco Flavored (Product C): Vape Free-Low Nicotine Tobacco
Salt-High Nicotine Tobacco Flavored (Product D): Vape Salt-High Tobacco | 1 |
| Product Sequence A Then B Then D Then C After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with one of the following: 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 random order.
Nicotine: Vape Free-Low nicotine unflavored
Vaporizer Device: Take puffs from vaporizer filled with different flavors
Salt-HIgh Nicotine Unflavored (Product B): Vape Salt-High nicotine unflavored
Free-Low Nicotine Tobacco Flavored (Product C): Vape Free-Low Nicotine Tobacco
Salt-High Nicotine Tobacco Flavored (Product D): Vape Salt-High Tobacco | 1 |
| Product Sequence B Then A Then D Thn C After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with one of the following: 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 random order.
Nicotine: Vape Free-Low nicotine unflavored
Vaporizer Device: Take puffs from vaporizer filled with different flavors
Salt-HIgh Nicotine Unflavored (Product B): Vape Salt-High nicotine unflavored
Free-Low Nicotine Tobacco Flavored (Product C): Vape Free-Low Nicotine Tobacco
Salt-High Nicotine Tobacco Flavored (Product D): Vape Salt-High Tobacco | 1 |
| Product Sequence B Then D Then C Then A After 8-10 hours after nicotine abstinence, participants attend 4 vaping sessions over 2-2.5 hours , 5-7 days apart. They are randomized to take 20 puffs over 10 minutes (1 puff every 30 seconds) of vaporized filled with one of the following: 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 random order.
Nicotine: Vape Free-Low nicotine unflavored
Vaporizer Device: Take puffs from vaporizer filled with different flavors
Salt-HIgh Nicotine Unflavored (Product B): Vape Salt-High nicotine unflavored
Free-Low Nicotine Tobacco Flavored (Product C): Vape Free-Low Nicotine Tobacco
Salt-High Nicotine Tobacco Flavored (Product D): Vape Salt-High Tobacco | 1 |
| Total | 15 |
Baseline characteristics
| Characteristic | Product Sequence D | Total | Product Sequence B Then D Then C Then A | Product Sequence B Then A Then D Thn C | Product Sequence A Then B Then D Then C | Product Sequence A Then C Then D Then B | Product Sequence C Then D Then A Then B | Product Sequence D Then A Then C Then B | Product Sequence A Then D Then B Then C | Product Sequence D Then C Then B Then A | Product Sequence A Then C | Product Sequence C Then D Then B Then A | Product Sequence D Then B Then A Then C | Product Sequence B Then C Then A Then D | Product Sequence A Then B Then C |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 26 years STANDARD_DEVIATION 2.8 | 28.7 years STANDARD_DEVIATION 8.7 | 32 years | 33 years | 32 years | 22 years | 26 years | 29 years | 23 years | 24 years | 21 years | 21 years | 37 years | 55 years | 24 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 2 Participants | 12 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants |
| Sex: Female, Male Male | 1 Participants | 10 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 13 |
| other Total, other adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 13 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 | 0 / 12 | 0 / 13 |
Outcome results
Primary
Area Under the Concentration-time Curve (AUC)
Area under the plasma nicotine concentration over time curve
Time frame: Samples were taken at minutes 0, then they started puffing and samples were taken 2, 4, 5, 6, 8, 10 minutes during puffing. Then, samples were taken at times 13, 15, 20, 30, and 120 minutes post puffing. The last dose occurred at week 4.
Population: All treated and eligible patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A: Unflavored Free-based Nicotine Form | Area Under the Concentration-time Curve (AUC) | 128.8 ng*min/mL | Standard Error 40.8 |
| B: Unflavored Salt-based Nicotine Form | Area Under the Concentration-time Curve (AUC) | 295.6 ng*min/mL | Standard Error 126.7 |
| C: Tobacco Flavor Free-based Nicotine Form | Area Under the Concentration-time Curve (AUC) | 177.3 ng*min/mL | Standard Error 51.7 |
| D: Tobacco Flavor Salt-based Nicotine Form | Area Under the Concentration-time Curve (AUC) | 199.7 ng*min/mL | Standard Error 71.7 |
Primary
Maximum Concentration of Nicotine in Plasma (Cmax)
The maximum nicotine concentration in blood plasma
Time frame: Samples were taken at minutes 0, then they started puffing and samples were taken 2, 4, 5, 6, 8, 10 minutes during puffing. Then, samples were taken at times 13, 15, 20, 30, and 120 minutes post puffing. The last dose occurred at week 4.
Population: All treated and eligible patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A: Unflavored Free-based Nicotine Form | Maximum Concentration of Nicotine in Plasma (Cmax) | 5.7 ng/mL | Standard Error 0.8 |
| B: Unflavored Salt-based Nicotine Form | Maximum Concentration of Nicotine in Plasma (Cmax) | 11.8 ng/mL | Standard Error 3.3 |
| C: Tobacco Flavor Free-based Nicotine Form | Maximum Concentration of Nicotine in Plasma (Cmax) | 6.7 ng/mL | Standard Error 1.3 |
| D: Tobacco Flavor Salt-based Nicotine Form | Maximum Concentration of Nicotine in Plasma (Cmax) | 8.1 ng/mL | Standard Error 1.7 |
Primary
Time to Maximum Concentration
Time to maximum nicotine concentration in the blood plasma
Time frame: Samples were taken at minutes 0, then they started puffing and samples were taken 2, 4, 5, 6, 8, 10 minutes during puffing. Then, samples were taken at times 13, 15, 20, 30, and 120 minutes post puffing. The last dose occurred at week 4.
Population: All treated and eligible patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A: Unflavored Free-based Nicotine Form | Time to Maximum Concentration | 11.5 minutes | Standard Error 1.6 |
| B: Unflavored Salt-based Nicotine Form | Time to Maximum Concentration | 9.8 minutes | Standard Error 1.5 |
| C: Tobacco Flavor Free-based Nicotine Form | Time to Maximum Concentration | 11.7 minutes | Standard Error 1.5 |
| D: Tobacco Flavor Salt-based Nicotine Form | Time to Maximum Concentration | 8.6 minutes | Standard Error 1.3 |
Secondary
Minnesota Nicotine Withdrawal Scale Change (Change From Pre- to Post-)
Minnesota Nicotine Withdrawal Scale Change Minnesota Nicotine Withdrawal scale measures 8 facets of withdrawal and results in a total score. We use change from 5 minutes Pre-puffing to 3 minutes post puffing session. Individual questions are scored 0 (none/better) to 4 (severe/worse). And then the scores are totaled. Positive change score = more withdrawal symptoms. Change score can range from -32 to 36). Positive change score = worse withdrawal symptoms Individual questions are scored 0 (none/better) to 4 (severe/worse). And then the scores are totaled.
Time frame: 5 minutes pre puffing and 3 minutes post puffing for 4 weeks
Population: All treated and eligible patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A: Unflavored Free-based Nicotine Form | Minnesota Nicotine Withdrawal Scale Change (Change From Pre- to Post-) | 0.5 score on a scale | Standard Error 0.7 |
| B: Unflavored Salt-based Nicotine Form | Minnesota Nicotine Withdrawal Scale Change (Change From Pre- to Post-) | 0.7 score on a scale | Standard Error 0.7 |
| C: Tobacco Flavor Free-based Nicotine Form | Minnesota Nicotine Withdrawal Scale Change (Change From Pre- to Post-) | 1.5 score on a scale | Standard Error 0.5 |
| D: Tobacco Flavor Salt-based Nicotine Form | Minnesota Nicotine Withdrawal Scale Change (Change From Pre- to Post-) | -0.5 score on a scale | Standard Error 0.7 |
Secondary
Perceived Harshness of Experimental Product Sampled
Subjective Measure of Perceived Harshness (Likert, 1-5: 1 = best outcome, 5 = worst outcome).
Time frame: 1 minute post puffing for 4 weeks
Population: All treated and eligible patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A: Unflavored Free-based Nicotine Form | Perceived Harshness of Experimental Product Sampled | 4.85 score on a scale | Standard Error 0.1 |
| B: Unflavored Salt-based Nicotine Form | Perceived Harshness of Experimental Product Sampled | 2.92 score on a scale | Standard Error 0.4 |
| C: Tobacco Flavor Free-based Nicotine Form | Perceived Harshness of Experimental Product Sampled | 4.62 score on a scale | Standard Error 0.1 |
| D: Tobacco Flavor Salt-based Nicotine Form | Perceived Harshness of Experimental Product Sampled | 3.08 score on a scale | Standard Error 0.4 |
Secondary
Perceived Liking of Experimental Product Sampled
Drug Effects Questionnaire Item #1 - perceived liking of the experimental product assessed by the question, Do you like any of the effects you are feeling right now? on a Likert scale from 0 (not at all) to 100 (extremely), with lower scores representing less liking of the experimental product. Mean is provided with possible scores between 0 and 100.
Time frame: 1 minute post puffing for 4 weeks
Population: All treated and eligible patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A: Unflavored Free-based Nicotine Form | Perceived Liking of Experimental Product Sampled | 45.9 score on a scale | Standard Error 5.2 |
| B: Unflavored Salt-based Nicotine Form | Perceived Liking of Experimental Product Sampled | 55.2 score on a scale | Standard Error 4 |
| C: Tobacco Flavor Free-based Nicotine Form | Perceived Liking of Experimental Product Sampled | 46.5 score on a scale | Standard Error 6 |
| D: Tobacco Flavor Salt-based Nicotine Form | Perceived Liking of Experimental Product Sampled | 52.5 score on a scale | Standard Error 5.4 |
Secondary
Perceived Satisfaction of Experimental Product Sampled
Nicotine Solution Rating Scale that orders each of the four products from 1 to 4, with 1 being least satisfying and 4 being most satisfying. Mean rank is provided with a possible score of 1 through 4.
Time frame: 120 minutes after session start on last session (session 4)
Population: All treated and eligible patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| A: Unflavored Free-based Nicotine Form | Perceived Satisfaction of Experimental Product Sampled | 3.08 score on a scale | Standard Error 0.3 |
| B: Unflavored Salt-based Nicotine Form | Perceived Satisfaction of Experimental Product Sampled | 3.75 score on a scale | Standard Error 0.4 |
| C: Tobacco Flavor Free-based Nicotine Form | Perceived Satisfaction of Experimental Product Sampled | 3.77 score on a scale | Standard Error 0.4 |
| D: Tobacco Flavor Salt-based Nicotine Form | Perceived Satisfaction of Experimental Product Sampled | 4.23 score on a scale | Standard Error 0.3 |
Other Pre-specified
Elasticity of Demand or Sensitivity to Price for Each Device Sampled
Demand elasticity , or sensitivity to price, is a behavioral economic measure of of the rate of purchasing decline over increasing cost for e-cigarettes. At each of the four sessions, participants experienced a marketplace with e-cigarette liquid prices of $1.63, $3.25, $6.50, and $13.00, while the prices of the other 11 tobacco products remained the same. Units purchased are transformed into mg of nicotine and nonlinear regression is used to estimate the purchasing when e-cigarettes are free/demand intensity, which is reported here. Higher scores indicate more sensitivity to price, also called inelastic demand.
Time frame: 60 minutes post puffing for 4 weeks
Population: All treated and eligible patients
| Arm | Measure | Value (MEAN) |
|---|---|---|
| A: Unflavored Free-based Nicotine Form | Elasticity of Demand or Sensitivity to Price for Each Device Sampled | 0.0005 mg nicotine per dollar |
| B: Unflavored Salt-based Nicotine Form | Elasticity of Demand or Sensitivity to Price for Each Device Sampled | 0.0004 mg nicotine per dollar |
| C: Tobacco Flavor Free-based Nicotine Form | Elasticity of Demand or Sensitivity to Price for Each Device Sampled | 0.0004 mg nicotine per dollar |
| D: Tobacco Flavor Salt-based Nicotine Form | Elasticity of Demand or Sensitivity to Price for Each Device Sampled | 0.0005 mg nicotine per dollar |
Other Pre-specified
Intensity of Demand or Estimated Milligrams E-cigarettes Purchased at Free Cost for Each Device Sampled
Demand intensity is a behavioral economic estimated measure of consumption at zero cost in a experimental marketplace focused on purchasing of tobacco and nicotine products over increasing price of one product while others stay the same price. Participants were asked to purchase tobacco products (12 options) for one week's use. At each of the four sessions, participants experienced a marketplace with e-cigarette liquid prices of $1.63, $3.25, $6.50, and $13.00, while the prices of the other 11 tobacco products remained the same. Units purchased are transformed into mg of nicotine and nonlinear regression is used to estimate the purchasing when e-cigarettes are free/demand intensity, which is reported here. Higher scores indicate more mg of nicotine from e-cigarettes were purchased
Time frame: 60 minutes post puffing for 4 weeks
Population: All treated and eligible patients
| Arm | Measure | Value (MEAN) |
|---|---|---|
| A: Unflavored Free-based Nicotine Form | Intensity of Demand or Estimated Milligrams E-cigarettes Purchased at Free Cost for Each Device Sampled | 908.3 mg of nicotine |
| B: Unflavored Salt-based Nicotine Form | Intensity of Demand or Estimated Milligrams E-cigarettes Purchased at Free Cost for Each Device Sampled | 1142 mg of nicotine |
| C: Tobacco Flavor Free-based Nicotine Form | Intensity of Demand or Estimated Milligrams E-cigarettes Purchased at Free Cost for Each Device Sampled | 785.5 mg of nicotine |
| D: Tobacco Flavor Salt-based Nicotine Form | Intensity of Demand or Estimated Milligrams E-cigarettes Purchased at Free Cost for Each Device Sampled | 985.8 mg of nicotine |
Other Pre-specified
Substitution Levels of Alternative Tobacco Products
Substitution is the slope of the line regressing consumption of the substitute product onto the price of cigarettes (cross-price elasticity). A positive coefficient indicates substitution (use of the substitute increases with increasing cigarette price). A negative value indicates complementarity (use of the substitute declines with increasing cigarette price). A value of 0 indicates no relationship.
Time frame: 120 minutes post puffing for 4 weeks
Population: All treated and eligible patients
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| A: Unflavored Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Marlboro Reds | 0 mg nicotine per dollar |
| A: Unflavored Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Revel Mint | 4.232 mg nicotine per dollar |
| A: Unflavored Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Revel Dark Mint | 0 mg nicotine per dollar |
| A: Unflavored Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | IQOS Tobacco | 0 mg nicotine per dollar |
| A: Unflavored Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | IQOS Menthol | 4.86 mg nicotine per dollar |
| A: Unflavored Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | JUUL Classic Tobacco | -0.000000000000 mg nicotine per dollar |
| A: Unflavored Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | JUUL Virginia Tobacco | 0 mg nicotine per dollar |
| A: Unflavored Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Camel Snus Frost | 0 mg nicotine per dollar |
| A: Unflavored Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Camel Snus Mellow | 0 mg nicotine per dollar |
| A: Unflavored Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | JUUL Menthol | 15.54 mg nicotine per dollar |
| A: Unflavored Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Marlboro Menthols | 0 mg nicotine per dollar |
| B: Unflavored Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | JUUL Menthol | 17.31 mg nicotine per dollar |
| B: Unflavored Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | JUUL Virginia Tobacco | 0 mg nicotine per dollar |
| B: Unflavored Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | JUUL Classic Tobacco | 8.167 mg nicotine per dollar |
| B: Unflavored Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Revel Dark Mint | 0 mg nicotine per dollar |
| B: Unflavored Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Revel Mint | 0.2371 mg nicotine per dollar |
| B: Unflavored Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Marlboro Reds | 0 mg nicotine per dollar |
| B: Unflavored Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Marlboro Menthols | 0 mg nicotine per dollar |
| B: Unflavored Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Camel Snus Mellow | 0 mg nicotine per dollar |
| B: Unflavored Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Camel Snus Frost | 0 mg nicotine per dollar |
| B: Unflavored Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | IQOS Menthol | 4.389 mg nicotine per dollar |
| B: Unflavored Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | IQOS Tobacco | 0.2552 mg nicotine per dollar |
| C: Tobacco Flavor Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | IQOS Menthol | 4.432 mg nicotine per dollar |
| C: Tobacco Flavor Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Marlboro Reds | 0 mg nicotine per dollar |
| C: Tobacco Flavor Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Marlboro Menthols | 0 mg nicotine per dollar |
| C: Tobacco Flavor Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | JUUL Virginia Tobacco | 0 mg nicotine per dollar |
| C: Tobacco Flavor Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Camel Snus Mellow | 0 mg nicotine per dollar |
| C: Tobacco Flavor Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | JUUL Classic Tobacco | 2.554 mg nicotine per dollar |
| C: Tobacco Flavor Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Camel Snus Frost | 0 mg nicotine per dollar |
| C: Tobacco Flavor Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Revel Dark Mint | 0 mg nicotine per dollar |
| C: Tobacco Flavor Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | IQOS Tobacco | 2.382 mg nicotine per dollar |
| C: Tobacco Flavor Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Revel Mint | 4.663 mg nicotine per dollar |
| C: Tobacco Flavor Free-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | JUUL Menthol | 14.75 mg nicotine per dollar |
| D: Tobacco Flavor Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | IQOS Tobacco | 1.813 mg nicotine per dollar |
| D: Tobacco Flavor Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | JUUL Menthol | 18.28 mg nicotine per dollar |
| D: Tobacco Flavor Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Marlboro Reds | 0 mg nicotine per dollar |
| D: Tobacco Flavor Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Camel Snus Mellow | 0 mg nicotine per dollar |
| D: Tobacco Flavor Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | IQOS Menthol | 2.43 mg nicotine per dollar |
| D: Tobacco Flavor Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Camel Snus Frost | 0 mg nicotine per dollar |
| D: Tobacco Flavor Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Marlboro Menthols | 0 mg nicotine per dollar |
| D: Tobacco Flavor Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | JUUL Classic Tobacco | -4.175 mg nicotine per dollar |
| D: Tobacco Flavor Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | JUUL Virginia Tobacco | 7.377 mg nicotine per dollar |
| D: Tobacco Flavor Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Revel Mint | 0.2371 mg nicotine per dollar |
| D: Tobacco Flavor Salt-based Nicotine Form | Substitution Levels of Alternative Tobacco Products | Revel Dark Mint | 0 mg nicotine per dollar |