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

NCT05335915 | Completed Phase 1

• 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

  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.

  Up to 6.5 hours

• Pharmacokinetics of nicotine as assessed by the AUC

  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 session and provides important insight into the abuse liability of a tobacco product.

  Up to 6.5 hours

• 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.

  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.

  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.

  6.5 hours

• Subjective ratings of "urge to smoke" as assessed by the Hughes-Hatsukami Withdrawal Questionnaire

  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.

  6.5 hours

• Subjective ratings of "craving to smoke" as assessed by the Hughes-Hatsukami Withdrawal Questionnaire

  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.

  6.5 hours

Secondary Outcomes (7)

• Pharmacokinetics of nicotine as assessed by the Tmax

  Up to 6.5 hours

• Tobacco withdrawal symptoms as assessed by the Tiffany-Drobes QSU brief-Factor 1

  6.5 hours

• Tobacco withdrawal symptoms as assessed by the Tiffany-Drobes QSU brief-Factor 2

  6.5 hours

• Topography as assessed by the total time of use

  2 hours

• The Direct Effects of Nicotine Scale (DENS)

  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

Study Officials

• Tory Spindle, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

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: September 5, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)