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

NCT05335915 | Completed Phase 1 Results

• 2 other identifiers: IRB003185601R01DA055962-01
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Nicotine Withdrawal; Nicotine Addiction; Drug Effect

Outcome Measures

Primary Outcomes (7)

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

  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.

  0 to 1 hour

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

  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.

  0 to 1 hour

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

  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.

  Up to 6.5 hours

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

  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.

  Up to 6.5 hours

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

  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.

  Up to 6.5 hours

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

  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.

  Up to 6.5 hours

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

  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.

  Up to 6.5 hours

Secondary Outcomes (7)

• Pharmacokinetics of Nicotine as Assessed by the Tmax

  Up to1 hour

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

  Up to 6.5 hours

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

  6.5 hours

• Topography as Assessed by the Total Time of Use

  2 hours

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

  6.5 hours

Study Arms (7)

Original/Tobacco Flavored Pouch (low nicotine dose)

EXPERIMENTAL

participants will use a tobacco flavored pouch (4mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions

Other: Nicotine

Original/Tobacco Flavored Pouch (high nicotine dose)

EXPERIMENTAL

participants will use a tobacco flavored pouch (8mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions

Other: Nicotine

Mint/Menthol Flavored Pouch (low nicotine dose)

EXPERIMENTAL

participants will use a mint/menthol flavored pouch (4mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions

Other: Nicotine

Mint/Menthol Flavored Pouch (high nicotine dose)

EXPERIMENTAL

participants will use a mint/menthol flavored pouch (8mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions

Other: Nicotine

Fruit Flavored Pouch (low nicotine dose)

EXPERIMENTAL

participants will use a fruit flavored pouch (4mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions

Other: Nicotine

Fruit Flavored Pouch (high nicotine dose)

EXPERIMENTAL

participants will use a fruit flavored pouch (8mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions

Other: Nicotine

Own brand cigarettes

ACTIVE COMPARATOR

participants will smoke participants' own brand of cigarettes under both controlled (experimenter-directed) and ad libitum use conditions

Other: Cigarette

Interventions

Nicotine OTHER

Nicotine pouches will be self-administered

Also known as: Tobacco

Fruit Flavored Pouch (high nicotine dose); Fruit Flavored Pouch (low nicotine dose); Mint/Menthol Flavored Pouch (high nicotine dose); Mint/Menthol Flavored Pouch (low nicotine dose); Original/Tobacco Flavored Pouch (high nicotine dose); Original/Tobacco Flavored Pouch (low nicotine dose)

Cigarette OTHER

Cigarette will be smoked

Also known as: Nicotine, Tobacco

Own brand cigarettes

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Johns Hopkins Behavioral Pharmacology Research Unit

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Tobacco Use Disorder

Interventions

Nicotine; Tobacco Products

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Smoking Devices; Manufactured Materials; Technology, Industry, and Agriculture

Results Point of Contact

• Title: Dr. Tory Spindle
• Organization: Johns Hopkins University School of Medicine

tspindle@jhmi.edu

4105500529

Study Officials

• Tory Spindle, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Masking Details: Double-blinded
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants will complete all dose conditions (study arms) in a randomized order

Study Record Dates

• First Submitted: April 12, 2022
• First Posted: April 20, 2022
• Study Start: July 27, 2022
• Primary Completion: August 29, 2025
• Study Completion: August 29, 2025
• Last Updated: July 23, 2026
• Results First Posted: July 23, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)