Acute Effects of Oral Nicotine Pouches

NCT07128329 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: IRB005024925R01DA055962-04
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The present human laboratory study will recruit cigarette smokers (n=60) and adult infrequent nicotine users (n=60) to complete two counterbalanced lab sessions in which the participants use nicotine pouches under controlled conditions. The investigators are recruiting both frequent and infrequent nicotine users because FDA regulates tobacco products based on a public health standard, meaning FDA must consider the impact a regulation may have on the population as a whole (e.g., people who use and do not use tobacco products currently).

Conditions

Nicotine Pharmacokinetic Study; Nicotine Pharmacodynamic Study; Nicotine Pouch Self-Administration

Keywords

Nicotine pouch; Cigarette smokers; Infrequent nicotine users; Outpatient; Zyn

Outcome Measures

Primary Outcomes (9)

• Pharmacokinetics - CMax for nicotine

  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.

  6.5 hours

• Pharmacokinetics - AUC for nicotine

  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.

  6.5 hours

• Drug Effect Questionnaire-Like Drug Effect

  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

• Drug Effect Questionnaire-pleasant Drug Effect

  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

• Drug Effect Questionnaire-take again

  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

• Topography - number of pouches used

  During the 2 hour ad libitum bout, primary topography variable will be collected - the total number of pouches used (range 0 - 5)

  2 hours

• Topography - duration of use

  During the 2 hour ad libitum bout, primary topography variable will be collected - total duration of use (range 0 - 2 hours).

  2 hours

• Hughes-Hatsukami Withdrawal Questionnaire

  The HHWS will be used to obtain subjective ratings of tobacco withdrawal outcomes among smokers including: "urge", "craving" "Anxious," "Depression," " Difficultly concentrating," "Drowsy," "Hunger," "Impatient," "Irritable," "Restlessness," "Desire for sweets". Scores for these items range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.

  6.5 hours

• Tiffany-Drobes Questionnaire on Smoking Urges (QSU) brief

  The QSU-brief will measure tobacco withdrawal symptoms in smokers using 10 items that form 2 factors: factor 1 (intention to smoke) and factor 2 (anticipation of withdrawal symptom relief). Mean score 0-5. Lower score is better.

  6.5 hours

Secondary Outcomes (5)

• Pharmacokinetics - Tmax for nicotine

  6.5 hours

• The Direct Effects of Nicotine Scale (DENS)

  6.5 hours

• Drug Effects Questionnaire (DEQ) - feel drug effect

  6.5 hours

• Drug Effects Questionnaire (DEQ) subjective effects- unpleasant effect

  6.5 hours

• Drug Effects Questionnaire (DEQ) subjective effects- dislike drug effect

  6.5 hours

Study Arms (2)

Pouch label version 1

ACTIVE COMPARATOR

Nicotine pouches with label 1

Drug: Nicotine Pouches

Pouch label version 2

EXPERIMENTAL

Nicotine pouches with label 2

Drug: Nicotine Pouches

Interventions

Nicotine Pouches DRUG

Nicotine pouches

Also known as: Zyn

Pouch label version 1; Pouch label version 2

Eligibility Criteria

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

You may qualify if:

• greater than or equal to 21 years old
• good general health based on screening procedures
• vital signs in normal range (resting heart rate less than 110bpm, systolic blood pressure less than 150mmHg, diastolic blood pressure less than 100mmHg)
• negative urine test for illicit drug use (excluding THC) and negative breath alcohol test at screening and before each session
• no self-reported prior use of oral nicotine pouches
• Not actively trying to quit smoking or using smoking cessation medication (e.g., nicotine replacement therapy)
• self-report currently smoking cigarettes daily
• exhaled breath CO greater than or equal to 10ppm and urine cotinine greater than 100 ng/ml at screening
• meet criteria for tobacco use disorder
• no self-reported regular use of other tobacco products (e.g., smokeless products, e-cigarettes) in the past 30 days
• self-report previously using nicotine/tobacco but no more than 100 lifetime uses across all routes of administration
• no self-reported nicotine/tobacco uses in the past 30 days
• urine cotinine less than 100 ng/ml at screening.

You may not qualify if:

• psychoactive drug use (aside from cannabis, nicotine, alcohol, or caffeine) in past month
• current use of OTC drugs, supplements/vitamins, or prescription medications that, in the opinion of medical staff, will impact safety
• currently have severe dependence for cannabis
• history of or current significant medical condition that, in the opinion of medical staff, will impact safety
• current psychiatric condition or substance use disorder (aside from tobacco use disorder for smokers), that, in the opinion of medical staff, will impact safety
• women who are pregnant, planning to become pregnant, or are breast-feeding

Sponsors & Collaborators

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

Study Sites (1)

Johns Hopkins University School of Medicine, Behavioral Pharmacology Research Unit (Bayview)

Baltimore, Maryland, 21224, United States

RECRUITING

Study Officials

• Tory Spindle, PhD

  Johns Hopkins University School of Medicine, Department of Psychiatry and Behavioral Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joseph Ciancio, PhD

CONTACT

(410) 550-0529; jcianci3@jh.edu

Lakshmi Kumar, PhD

CONTACT

(410) 550-1928; lkumar6@jh.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Research program coordinators
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Mixed between/within-subjects crossover design with two groups of participants (cigarette smokers and infrequent nicotine users). Participants complete all experimental sessions, serving as their own control.

Study Record Dates

• First Submitted: August 13, 2025
• First Posted: August 18, 2025
• Study Start: November 21, 2025
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: February 17, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)