Pharmacokinetics and Pharmacodynamics of Different Nicotine Salt Concentration Vape System Pods and Free-base Nicotine

Randomized Crossover Study Comparing the Pharmacokinetics and Pharmacodynamics of Two Different Nicotine Salt Concentrations and Free-base Nicotine Using an Open Vape Pod System

Comparison of the pharmacokinetics and pharmacodynamics of two different nicotine salt concentrations and free-base nicotine using an open vape pod system

Study Overview

• Status: Completed
• Conditions: Nicotine Dependence
• Intervention / Treatment: Other: standardized vaping protocol

Detailed Description

On each study day, one puff will be taken with the assigned product every 30 seconds (total of 10 puffs). Blood samples will be collected to measure nicotine 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff. Heart rate and blood pressure will be measured 15 minutes before and 2, 10, 15, 30, 60, 120, and 180 minutes after the last puff. Post-use withdrawal, craving, reward, and satisfaction will be assessed 10 minutes and 1 and 3 hours after the last puff using the modified Minnesota Nicotine Withdrawal Scale (MNWS), the Tiffany Questionnaire on Smoking Urges (QSU), and the Positive and Negative Affect Schedule (PANAS) questionnaires. Respiratory symptoms will be assessed at baseline and 5 minutes after the last puff. Ten minutes post-use, the direct effects of the assigned product (e.g. satisfying, calming, pleasant, vape another one right now) will also be assessed using visual analog scales.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • BE
    • Bern, BE, Switzerland, 3010
      • Inselspital, University Hospital Bern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men or women, age 18 or older at screening, who have used electronic cigarettes and/or smoked at least 5 cigarettes per day in the past 30 days
• Saliva cotinine of > 50 ng/mL at screening
• No clinically significant findings on the physical examination at screening
• Ability to communicate well with the investigator and to understand and comply with the requirements of the study
• Women of child-bearing age: willingness of using a reliable contraception method during the study
• Signed informed consent

Exclusion Criteria:

• Known hypersensitivity/allergy to a content of the e-liquid
• Pregnancy or breast feeding
• BMI < 18 or > 28 kg/m2 at screening
• History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening
• Loss of ≥ 250 ml of blood within 3 months prior to screening, including blood donation
• Treatment with an investigational drug within 30 days prior to screening
• Treatment with prescribed or over-the-counter (OTC) medications with potential influence on CYP2A6 function within 1 week prior to screening (with the exception of contraception)
• History or clinical evidence of any disease (e.g. gastrointestinal tract-disease) and/or existence of any surgical or medical condition, which in the opinion of the investigator might interfere with the absorption, distribution, metabolism or excretion of the study drugs, or which might increase the risk for toxicity
• Legal incapacity or limited legal capacity at screening
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Nicotine salt 20 mg/mL; Vaping of nicotine salt e-liquids with a nicotine concentration of 20 mg/mL.	Other: standardized vaping protocol; The following questionnaires will first be completed: Modified Minnesota Nicotine Withdrawal Scale, Tiffany Questionnaire on Smoking Urges-Brief total (global) craving score, Positive and Negative Affect Schedule. The assigned product will then be given to the participant, and one puff will be taken every 30 seconds (total of 10 puffs). Blood samples will be collected 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff. Heart rate and blood pressure will be measured 15 minutes before and 2, 10, 15, 30, 60, 120, and 180 minutes after the last puff. Post-use withdrawal, craving, reward, and satisfaction will be assessed 10 minutes and 1 and 3 hours after the last puff. Respiratory Symptoms will be assessed at baseline and 5 minutes after the last puff. Ten minutes post-use, the direct effects will also be assessed.
OTHER: Nicotine salt 40 mg/mL; Vaping of nicotine salt e-liquids with a nicotine concentration of 40 mg/mL.	Other: standardized vaping protocol; The following questionnaires will first be completed: Modified Minnesota Nicotine Withdrawal Scale, Tiffany Questionnaire on Smoking Urges-Brief total (global) craving score, Positive and Negative Affect Schedule. The assigned product will then be given to the participant, and one puff will be taken every 30 seconds (total of 10 puffs). Blood samples will be collected 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff. Heart rate and blood pressure will be measured 15 minutes before and 2, 10, 15, 30, 60, 120, and 180 minutes after the last puff. Post-use withdrawal, craving, reward, and satisfaction will be assessed 10 minutes and 1 and 3 hours after the last puff. Respiratory Symptoms will be assessed at baseline and 5 minutes after the last puff. Ten minutes post-use, the direct effects will also be assessed.
OTHER: Free-base nicotine 20 mg/mL; Vaping of free-base nicotine e-liquids with a nicotine concentration of 20 mg/mL.	Other: standardized vaping protocol; The following questionnaires will first be completed: Modified Minnesota Nicotine Withdrawal Scale, Tiffany Questionnaire on Smoking Urges-Brief total (global) craving score, Positive and Negative Affect Schedule. The assigned product will then be given to the participant, and one puff will be taken every 30 seconds (total of 10 puffs). Blood samples will be collected 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff. Heart rate and blood pressure will be measured 15 minutes before and 2, 10, 15, 30, 60, 120, and 180 minutes after the last puff. Post-use withdrawal, craving, reward, and satisfaction will be assessed 10 minutes and 1 and 3 hours after the last puff. Respiratory Symptoms will be assessed at baseline and 5 minutes after the last puff. Ten minutes post-use, the direct effects will also be assessed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nicotine Peak Plasma Concentration (Cmax)	Comparison of nicotine Cmax between groups	Blood samples collection: 15 minutes before and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the plasma concentration versus time curve (AUC)	Comparison of the nicotine AUC between groups	Blood samples collection: 15 minutes before and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
Time at which the Cmax is observed (Tmax)	Comparison of the nicotine Tmax between groups	Blood samples collection: 15 minutes before and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
Elimination half-life (t1/2)	Comparison of t1/2 between groups	Blood samples collection: 15 minutes before and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
Genotyping of the hepatic cytochrome P450 enzyme CYP2A6	CYP2A6 genotype (allele variants)	Blood sample collection during first session
Nicotine metabolite ratio (NMR)	Nicotine clearance assessed using 3'-hydroxycotinine/cotinine ratios	Assessed at screening visit
Modified Minnesota Nicotine Withdrawal Scale (MNWS)	Excluding items relating to sleep disturbance and constipation, including eight items (angry/irritable/frustrated, anxious/nervous, depressed mood/sad, desire or craving to smoke, difficulty concentrating, increased appetite/hungry, restless and impatient), rated on a 0=none to 4=severe scale	Baseline, 10 minutes and 1 and 3 hours after the last puff
Tiffany Questionnaire on Smoking Urges-Brief (QSU) total (global) craving score	Mean of ten items, rated on a 1=strongly disagree to 7=strongly agree scale	Baseline, 10 minutes and 1 and 3 hours after the last puff
Positive and Negative Affect Schedule (PANAS)	Including items assigned as Positive or Negative Affect (each score is the sum of ten items, rated on a 1=very slightly/not at all to 5=extremely scale)	Baseline, 10 minutes and 1 and 3 hours after the last puff
Respiratory symptoms	Yes/no: shortness of breath, wheezing, cough, phlegm	At baseline and 5 minutes after the last puff
Direct effects	E.g. satisfying, calming, pleasant, vape another one right now, assessed using visual analog scales (0-100 mm) with a single word scored from left (not at all) to right (extremely)	Ten minutes post-use
Heart rate	Heart rate measurements (bpm)	15 minutes before and 2, 10, 15, 30, 60, 120, and 180 minutes after the last puff
Systolic blood pressure	Systolic blood pressure measurements (mmHg)	15 minutes before and 2, 10, 15, 30, 60, 120, and 180 minutes after the last puff
Diastolic blood pressure	Diastolic blood pressure measurements (mmHg)	15 minutes before and 2, 10, 15, 30, 60, 120, and 180 minutes after the last puff

Collaborators and Investigators

• Sponsor: University Hospital Inselspital, Berne
• Collaborators: University of Bern
• Investigators: Principal Investigator: Evangelia Liakoni, MD, Sponsor: Inselspital, Bern University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 19, 2022
• Primary Completion (ACTUAL): August 30, 2022
• Study Completion (ACTUAL): August 30, 2022

Study Registration Dates

• First Submitted: November 12, 2019
• First Submitted That Met QC Criteria: November 18, 2019
• First Posted (ACTUAL): November 20, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 7, 2022
• Last Update Submitted That Met QC Criteria: September 5, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: pharmacokinetics; pharmacodynamics; nicotine
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder
• Other Study ID Numbers: Nicotine PK PD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No