Skip to main content
OpenTrials
Completed

NCT Number: NCT05335915

Acute Pharmacokinetic and Pharmacodynamic Effects of "Tobacco-Free" Oral Nicotine Pouches in Smokers

The purpose of the present study is to examine the pharmacokinetics and pharmacodynamics of "tobacco-free" oral nicotine pouches, at various doses and flavors, in healthy adult smokers. The study will utilize a within-subjects, double-blind design. Upon enrollment, participants will complete 7 dosing conditions: tobacco-flavored pouch (low or high nicotine dose), mint/menthol-flavored pouch (low or high nicotine dose), and fruit-flavored pouch (low or high nicotine dose); participants will also complete a condition where the participants will smoke participants' preferred brand of cigarettes. In each experimental session, participants will complete 2 product-use bouts. In bout 1, the participants will use a single product (pouch or cigarette) for a fixed period under controlled conditions. In bout 2, participants will be given 2 hours to use participants' assigned product ad libitum.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Nicotine Withdrawal Chemically-Induced Disorders Drug Effect Mental Disorders Nicotine Addiction Substance-Related Disorders Tobacco Use Disorder

Age range

21 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Johns Hopkins Behavioral Pharmacology Research Unit

Baltimore, Maryland, 21224, United States

About this study

The purpose of the present study is to examine the pharmacokinetics and pharmacodynamics of "tobacco-free" oral nicotine pouches, at various doses and flavors, in healthy adult smokers. The study will utilize a within-subjects, double-blind design. Upon enrollment, participants will complete 7 dosing conditions: tobacco-flavored pouch (low or high nicotine dose), mint/menthol-flavored pouch (low or high nicotine dose), and fruit-flavored pouch (low or high nicotine dose); participants will also complete a condition where the participants will smoke participants' preferred brand of cigarettes. In each experimental session, participants will complete 2 product-use bouts. In bout 1, the participants will use a single product (pouch or cigarette) for a fixed period under controlled conditions. In bout 2, participants will be given 2 hours to use participants' assigned product ad libitum. Blood specimens will be obtained throughout the sessions to characterize the pharmacokinetics of nicotine and various pharmacodynamic outcomes (subjective drug effects, tobacco withdrawal symptoms, vital signs) will also be assessed. These procedures will be completed 7 separate times (on separate visits) by each participant (sessions will be separated by at least 48 hours).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • ≥ 21 years old
  • good general health based on screening procedures (e.g., physical exam, blood testing)
  • vital signs in normal range (resting heart rate less than 100bpm, systolic blood pressure less than 150mmHg, diastolic blood pressure less than 90mmHg)
  • negative urine test for illicit drug use (excluding THC) and negative breath alcohol test at screening and before each session
  • self-report currently smoking daily
  • self-report at least a one year history of regular smoking
  • exhaled breath CO greater than or equal to 10ppm and urine cotinine greater than 100 ng/ml at screening
  • meet criteria for at least mild tobacco use disorder
  • no self-reported regular use of other tobacco products (e.g., smokeless products, e-cigarettes) in the past 30 days
  • no self-reported prior use of novel oral nicotine pouches
  • exhaled breath CO less than 10 ppm upon arrival for each study session.

Exclusion criteria

  • Psychoactive drug use (aside from cannabis, nicotine, alcohol, or caffeine) in past month
  • Current use of over-the-counter (OTC) drugs, supplements/vitamins, or prescription medications that, in the opinion of the investigators or medical staff, will impact safety
  • Use of cannabis >4 times per week
  • History of or current significant medical condition that, in the opinion of the investigators or medical staff, will impact safety
  • Current psychiatric condition or substance use disorder (aside from tobacco use disorder) that, in the opinion of the investigators or medical staff, will impact safety or study outcomes
  • Women who are pregnant, planning to become pregnant, or are breast-feeding
  • Currently seeking treatment to quit smoking or currently using a nicotine/tobacco cessation product.
  • Enrollment in another clinical trial in the past 30 days

Treatment and study plan

Nicotine

Other

Nicotine pouches will be self-administered

Other names: Tobacco

Cigarette

Other

Cigarette will be smoked

Other names: Nicotine, Tobacco

Primary outcomes

  1. Pharmacokinetics of Nicotine as Assessed by the Cmax (20-min Directed Bout)

    Time frame: 0 to 1 hour

    Blood plasma samples will be collected and sent to a designated laboratory for quantitative analysis of nicotine. Maximum concentration (Cmax), is the highest plasma nicotine concentration reached during a session and provides important insight into the abuse liability of a tobacco product. Bout 1 (20min directed use) Cmax was calculated based on post-baseline blood timepoints which include 10 minutes, 20 minutes, 30 minutes, and 1 hour after bout 1 dosing.

  2. Pharmacokinetics of Nicotine as Assessed by the AUC (20 Min Directed Bout)

    Time frame: 0 to 1 hour

    Blood plasma samples will be collected and sent to a designated laboratory for quantitative analysis of nicotine. Area under the curve (AUC), represents the total nicotine exposure during an entire nicotine use period and provides important insight into the abuse liability of a tobacco product. Data is reported as the mean (SD) change from baseline. Bout 1 (20min directed use) AUC was calculated based on post-baseline blood timepoints which include 10 minutes, 20 minutes, 30 minutes, and 1 hour after bout 1 dosing.

  3. Peak Change From Baseline Subjective Ratings of "Like Drug Effect" as Assessed by the Drug Effect Questionnaire

    Time frame: Up to 6.5 hours

    The DEQ will be used to obtain subjective ratings of "like drug effect". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation with higher score indicating greater liking. Data is reported as mean (SD) change from baseline. A peak change from baseline score was calculated based on post-baseline timepoints which include 20 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 3.5 hours, 4.5 hours, and 6.5 hours after bout 1 dosing.

  4. Subjective Ratings of "Pleasant Drug Effect" as Assessed by the Drug Effect Questionnaire

    Time frame: Up to 6.5 hours

    The DEQ will be used to obtain subjective ratings of "pleasant drug effect". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation with higher score indicating greater "pleasant drug effect". A peak change from baseline score was calculated based on post-baseline timepoints which include 20 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 3.5 hours, 4.5 hours, and 6.5 hours after bout 1 dosing.

  5. Subjective Ratings of "Take Again" as Assessed by the Drug Effect Questionnaire

    Time frame: Up to 6.5 hours

    The DEQ will be used to obtain subjective ratings of "take again". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation, with higher score indicating greater "take again" rating. A peak change from baseline score was calculated based on post-baseline timepoints which include 20 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 3.5 hours, 4.5 hours, and 6.5 hours after bout 1 dosing.

  6. Subjective Ratings of "Urge to Smoke" as Assessed by the Hughes-Hatsukami Withdrawal Questionnaire (Change From Baseline)

    Time frame: Up to 6.5 hours

    The HHWS will be used to obtain subjective ratings of "urge to smoke". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation with higher score indicating greater "urge to smoke". A peak change from baseline score was calculated based on post-baseline timepoints which include 20 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 3.5 hours, 4.5 hours, and 6.5 hours after bout 1 dosing.

  7. Subjective Ratings of "Craving to Smoke" as Assessed by the Hughes-Hatsukami Withdrawal Questionnaire (Change From Baseline)

    Time frame: Up to 6.5 hours

    The HHWS will be used to obtain subjective ratings of "craving to smoke". Score range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation, with higher score indicating greater "craving to smoke". A peak change from baseline score was calculated based on post-baseline timepoints which include 20 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 3.5 hours, 4.5 hours, and 6.5 hours after bout 1 dosing.

Secondary outcomes

  1. Pharmacokinetics of Nicotine as Assessed by the Tmax

    Time frame: Up to1 hour

    Blood plasma samples will be collected and sent to a designated laboratory for quantitative analysis of nicotine. Time to maximum concentration (Tmax), is the time (in minutes) to reach Cmax. This is another measure relevant for abuse liability. Tmax for bout 1 was calculated based on post-baseline blood timepoints which include 20 minutes, 30 minutes, and 1 hour after bout 1 dosing.

  2. Tobacco Withdrawal Symptoms as Assessed by the Tiffany-Drobes QSU Brief-Factor 1 (Change From Baseline)

    Time frame: Up to 6.5 hours

    The QSU-brief factor 1 (intention to smoke) measures tobacco withdrawal symptoms using 5 items; scores are summed to produce a single score ranging from 0 to 30. Higher scores indicates greater withdrawal symptoms. A peak change from baseline score was calculated based on post-baseline timepoints which include 20 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 3.5 hours, 4.5 hours, and 6.5 hours after bout 1 dosing.

  3. Tobacco Withdrawal Symptoms as Assessed by the Tiffany-Drobes QSU Brief-Factor 2 (Change From Baseline)

    Time frame: 6.5 hours

    The QSU-brief factor 2 (anticipation of relief) measures tobacco withdrawal symptoms using 5 items; scores are summed to produce a single score ranging from 0 to 24. Higher scores indicates greater/worse withdrawal symptoms.

  4. Topography as Assessed by the Total Time of Use

    Time frame: 2 hours

    During the 2 hour ad libitum bout, topography will be collected. The total time of use (out of 2 hours) will be assessed.

  5. The Direct Effects of Nicotine Scale (DENS) (Change From Baseline)

    Time frame: 6.5 hours

    The DENS will assess nicotine-specific effects. Scores on all items range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation. Higher scores indicates stronger (better) nicotine related effects.

  6. Perceived Strength of Effects as Assessed by the Drug Effect Questionnaire

    Time frame: Up to 6.5 hours

    The DEQ will assess subjective ratings for "feel drug effect". Scores range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation with higher score indicating greater "feel drug effect". Higher scores indicates stronger (better) effects. A peak change from baseline score was calculated based on post-baseline timepoints which include 20 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 3.5 hours, 4.5 hours, and 6.5 hours after bout 1 dosing.

  7. Negative and Aversive Effects as Assessed by the Drug Effect Questionnaire

    Time frame: Up to 6.5 hours

    The DEQ will assess subjective ratings for "dislike drug effect". Scores range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation with higher score indicating a stronger (worse) perception of aversive or unpleasant drug effects. A peak change from baseline score was calculated based on post-baseline timepoints which include 20 minutes, 30 minutes, 1 hour, 1.5 hours, 2 hours, 3 hours, 3.5 hours, 4.5 hours, and 6.5 hours after bout 1 dosing.

Sponsors and collaborators

Lead sponsor

Johns Hopkins University

Other

Collaborators

  • National Institute on Drug Abuse (NIDA)

Registry information

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
Apr 20, 2022
Registry last updated
Jul 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.