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.

Study Overview

• Status: Recruiting
• Conditions: Drug Effect; Nicotine Addiction; Nicotine Withdrawal
• Intervention / Treatment: Other: Nicotine; Other: Cigarette

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Mikahla McDeavitt; Phone Number: 410-550-0050; Email: mmcdeav1@jhmi.edu
• Study Contact Backup: Name: Tory Spindle, PhD; Phone Number: 410-550-0529; Email: tspindle@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Recruiting
      • Johns Hopkins Behavioral Pharmacology Research Unit
      • Contact: Tory Spindle, PhD; Phone Number: 410-550-0529; Email: tspindle@jhmi.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. ≥ 21 years old
2. good general health based on screening procedures (e.g., physical exam, blood testing)
3. vital signs in normal range (resting heart rate less than 100bpm, systolic blood pressure less than 150mmHg, diastolic blood pressure less than 90mmHg)
4. negative urine test for illicit drug use (excluding THC) and negative breath alcohol test at screening and before each session
5. self-report currently smoking daily
6. self-report at least a one year history of regular smoking
7. exhaled breath CO greater than or equal to 10ppm and urine cotinine greater than 100 ng/ml at screening
8. meet criteria for at least mild tobacco use disorder
9. no self-reported regular use of other tobacco products (e.g., smokeless products, e-cigarettes) in the past 30 days
10. no self-reported prior use of novel oral nicotine pouches
11. exhaled breath CO less than 10 ppm upon arrival for each study session.

Exclusion Criteria:

1. Psychoactive drug use (aside from cannabis, nicotine, alcohol, or caffeine) in past month
2. 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
3. Use of cannabis >4 times per week
4. History of or current significant medical condition that, in the opinion of the investigators or medical staff, will impact safety
5. 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
6. Women who are pregnant, planning to become pregnant, or are breast-feeding
7. Currently seeking treatment to quit smoking or currently using a nicotine/tobacco cessation product.
8. Enrollment in another clinical trial in the past 30 days

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Original/Tobacco Flavored Pouch (low nicotine dose); participants will use a tobacco flavored pouch (4mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions	Other: Nicotine; Nicotine pouches will be self-administered; Other Names: Tobacco
Experimental: Original/Tobacco Flavored Pouch (high nicotine dose); participants will use a tobacco flavored pouch (8mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions	Other: Nicotine; Nicotine pouches will be self-administered; Other Names: Tobacco
Experimental: Mint/Menthol Flavored Pouch (low nicotine dose); participants will use a mint/menthol flavored pouch (4mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions	Other: Nicotine; Nicotine pouches will be self-administered; Other Names: Tobacco
Experimental: Mint/Menthol Flavored Pouch (high nicotine dose); participants will use a mint/menthol flavored pouch (8mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions	Other: Nicotine; Nicotine pouches will be self-administered; Other Names: Tobacco
Experimental: Fruit Flavored Pouch (low nicotine dose); participants will use a fruit flavored pouch (4mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions	Other: Nicotine; Nicotine pouches will be self-administered; Other Names: Tobacco
Experimental: Fruit Flavored Pouch (high nicotine dose); participants will use a fruit flavored pouch (8mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions	Other: Nicotine; Nicotine pouches will be self-administered; Other Names: Tobacco
Active Comparator: Own brand cigarettes; participants will smoke participants' own brand of cigarettes under both controlled (experimenter-directed) and ad libitum use conditions	Other: Cigarette; Cigarette will be smoked; Other Names: Tobacco; Nicotine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of nicotine as assessed by the Tmax	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.	Up to 6.5 hours
Tobacco withdrawal symptoms as assessed by the Tiffany-Drobes QSU brief-Factor 1	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	6.5 hours
Tobacco withdrawal symptoms as assessed by the Tiffany-Drobes QSU brief-Factor 2	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	6.5 hours
Topography as assessed by the total time of use	During the 2 hour ad libitum bout, topography will be collected. The total time of use (out of 2 hours) will be assessed.	2 hours
The Direct Effects of Nicotine Scale (DENS)	The DENS will assess nicotine-specific effects. Scores range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.	6.5 hours
Perceived strength of effects as assessed by the Drug Effect Questionnaire	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.	6.5 hours
Negative and aversive effects as assessed by the Drug Effect Questionnaire	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.	6.5 hours

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Tory Spindle, PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): July 27, 2022
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2025

Study Registration Dates

• First Submitted: April 12, 2022
• First Submitted That Met QC Criteria: April 12, 2022
• First Posted (Actual): April 20, 2022

Study Record Updates

• Last Update Posted (Estimated): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 13, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Ganglionic Stimulants; Nicotinic Agonists; Cholinergic Agonists; Nicotine
• Other Study ID Numbers: IRB00318560; 1R01DA055962-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes