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

Primary Purpose

Nicotine Withdrawal, Nicotine Addiction, Drug Effect

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Nicotine
Cigarette
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Nicotine Withdrawal

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  1. over 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 160mmHg, 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 10 or more cigarettes per day
  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 moderate to severe tobacco use disorder (DSM-V and FTND)
  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 >2 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

Sites / Locations

  • Johns Hopkins Behavioral Pharmacology Research UnitRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Active Comparator

Arm Label

Original/Tobacco Flavored Pouch (low nicotine dose)

Original/Tobacco Flavored Pouch (high nicotine dose)

Mint/Menthol Flavored Pouch (low nicotine dose)

Mint/Menthol Flavored Pouch (high nicotine dose)

Fruit Flavored Pouch (low nicotine dose)

Fruit Flavored Pouch (high nicotine dose)

Own brand cigarettes

Arm Description

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

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

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.
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.
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.
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.
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.
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.
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.

Secondary Outcome Measures

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.
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
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
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.
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.
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.
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.

Full Information

First Posted
April 12, 2022
Last Updated
December 7, 2022
Sponsor
Johns Hopkins University
Collaborators
National Institute on Drug Abuse (NIDA)
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1. Study Identification

Unique Protocol Identification Number
NCT05335915
Brief Title
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

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 27, 2022 (Actual)
Primary Completion Date
September 1, 2025 (Anticipated)
Study Completion Date
September 1, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
National Institute on Drug Abuse (NIDA)

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nicotine Withdrawal, Nicotine Addiction, Drug Effect

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
Model Description
All participants will complete all dose conditions (study arms) in a randomized order
Masking
ParticipantCare Provider
Masking Description
Double-blinded
Allocation
Randomized
Enrollment
56 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Original/Tobacco Flavored Pouch (low nicotine dose)
Arm Type
Experimental
Arm Description
participants will use a tobacco flavored pouch (4mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions
Arm Title
Original/Tobacco Flavored Pouch (high nicotine dose)
Arm Type
Experimental
Arm Description
participants will use a tobacco flavored pouch (8mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions
Arm Title
Mint/Menthol Flavored Pouch (low nicotine dose)
Arm Type
Experimental
Arm Description
participants will use a mint/menthol flavored pouch (4mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions
Arm Title
Mint/Menthol Flavored Pouch (high nicotine dose)
Arm Type
Experimental
Arm Description
participants will use a mint/menthol flavored pouch (8mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions
Arm Title
Fruit Flavored Pouch (low nicotine dose)
Arm Type
Experimental
Arm Description
participants will use a fruit flavored pouch (4mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions
Arm Title
Fruit Flavored Pouch (high nicotine dose)
Arm Type
Experimental
Arm Description
participants will use a fruit flavored pouch (8mg nicotine dose)under both controlled (experimenter-directed) and ad libitum use conditions
Arm Title
Own brand cigarettes
Arm Type
Active Comparator
Arm Description
participants will smoke participants' own brand of cigarettes under both controlled (experimenter-directed) and ad libitum use conditions
Intervention Type
Other
Intervention Name(s)
Nicotine
Other Intervention Name(s)
Tobacco
Intervention Description
Nicotine pouches will be self-administered
Intervention Type
Other
Intervention Name(s)
Cigarette
Other Intervention Name(s)
Nicotine, Tobacco
Intervention Description
Cigarette will be smoked
Primary Outcome Measure Information:
Title
Pharmacokinetics of nicotine as assessed by the Cmax
Description
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.
Time Frame
Up to 6.5 hours
Title
Pharmacokinetics of nicotine as assessed by the AUC
Description
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.
Time Frame
Up to 6.5 hours
Title
Subjective ratings of "Like Drug Effect" as assessed by the Drug Effect Questionnaire
Description
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.
Time Frame
6.5 hours
Title
Subjective ratings of "Pleasant Drug Effect" as assessed by the Drug Effect Questionnaire
Description
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.
Time Frame
6.5 hours
Title
Subjective ratings of "take again" as assessed by the Drug Effect Questionnaire
Description
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.
Time Frame
6.5 hours
Title
Subjective ratings of "urge to smoke" as assessed by the Hughes-Hatsukami Withdrawal Questionnaire
Description
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.
Time Frame
6.5 hours
Title
Subjective ratings of "craving to smoke" as assessed by the Hughes-Hatsukami Withdrawal Questionnaire
Description
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.
Time Frame
6.5 hours
Secondary Outcome Measure Information:
Title
Pharmacokinetics of nicotine as assessed by the Tmax
Description
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.
Time Frame
Up to 6.5 hours
Title
Tobacco withdrawal symptoms as assessed by the Tiffany-Drobes QSU brief-Factor 1
Description
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
Time Frame
6.5 hours
Title
Tobacco withdrawal symptoms as assessed by the Tiffany-Drobes QSU brief-Factor 2
Description
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
Time Frame
6.5 hours
Title
Topography as assessed by the total time of use
Description
During the 2 hour ad libitum bout, topography will be collected. The total time of use (out of 2 hours) will be assessed.
Time Frame
2 hours
Title
The Direct Effects of Nicotine Scale (DENS)
Description
The DENS will assess nicotine-specific effects. Scores range from 0 (none) to 100 (extreme) using a 100mm line anchored with none/extreme designation.
Time Frame
6.5 hours
Title
Perceived strength of effects as assessed by the Drug Effect Questionnaire
Description
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.
Time Frame
6.5 hours
Title
Negative and aversive effects as assessed by the Drug Effect Questionnaire
Description
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.
Time Frame
6.5 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: ≥ 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. Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Tory Spindle, PhD
Phone
410-550-0529
Email
tspindle@jhmi.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Mikahla McDeavitt
Phone
410-550-0050
Email
mmcdeav1@jhmi.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tory Spindle, PhD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins Behavioral Pharmacology Research Unit
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21224
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tory Spindle, PhD
Phone
410-550-0529
Email
tspindle@jhmi.edu

12. IPD Sharing Statement

Plan to Share IPD
No

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

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