Clinical trial NCT05335915: Acute Pharmacokinetic and Pharmacodynamic Effects of "Tobacco-Free" Oral Nicotine Pouches in Smokers
Official title: Acute Pharmacokinetic and Pharmacodynamic Effects of "Tobacco-Free" Oral Nicotine Pouches in Smokers
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Nicotine Withdrawal
Nicotine Addiction
Drug Effect
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2022-04-20
Enrollment: 90
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: All participants will complete all dose conditions (study arms) in a randomized order
Primary purpose: BASIC_SCIENCE

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.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Pharmacokinetics of nicotine as assessed by the Cmax
timeFrame: Up to 6.5 hours
measure: Pharmacokinetics of nicotine as assessed by the AUC
timeFrame: Up to 6.5 hours
measure: Subjective ratings of "Like Drug Effect" as assessed by the Drug Effect Questionnaire
timeFrame: 6.5 hours
measure: Subjective ratings of "Pleasant Drug Effect" as assessed by the Drug Effect Questionnaire
timeFrame: 6.5 hours
measure: Subjective ratings of "take again" as assessed by the Drug Effect Questionnaire
timeFrame: 6.5 hours
measure: Subjective ratings of "urge to smoke" as assessed by the Hughes-Hatsukami Withdrawal Questionnaire
timeFrame: 6.5 hours
measure: Subjective ratings of "craving to smoke" as assessed by the Hughes-Hatsukami Withdrawal Questionnaire
timeFrame: 6.5 hours
Secondary outcomes:
measure: Pharmacokinetics of nicotine as assessed by the Tmax
timeFrame: Up to 6.5 hours
measure: Tobacco withdrawal symptoms as assessed by the Tiffany-Drobes QSU brief-Factor 1
timeFrame: 6.5 hours
measure: Tobacco withdrawal symptoms as assessed by the Tiffany-Drobes QSU brief-Factor 2
timeFrame: 6.5 hours
measure: Topography as assessed by the total time of use
timeFrame: 2 hours
measure: The Direct Effects of Nicotine Scale (DENS)
timeFrame: 6.5 hours
measure: Perceived strength of effects as assessed by the Drug Effect Questionnaire
timeFrame: 6.5 hours
measure: Negative and aversive effects as assessed by the Drug Effect Questionnaire
timeFrame: 6.5 hours
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Behavioral Pharmacology Research Unit
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Tory Spindle, PhD
role: PRINCIPAL_INVESTIGATOR
References: