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

Nicotine Dependence Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04170907
• Other study ID #: Nicotine PK PD
• Status: Completed
• Phase: N/A
• Start date: April 19, 2022
• Est. completion date: August 30, 2022

Study information

• Verified date: April 2022
• Source: University Hospital Inselspital, Berne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: August 30, 2022
• Est. primary completion date: August 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Nicotine Dependence
• Tobacco Use Disorder

Intervention

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.

Locations

Country	Name	City	State
Switzerland	Inselspital, University Hospital Bern	Bern	BE

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne	University of Bern

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	Genotyping of the hepatic cytochrome P450 enzyme CYP2A6	CYP2A6 genotype (allele variants)	Blood sample collection during first session
Secondary	Nicotine metabolite ratio (NMR)	Nicotine clearance assessed using 3'-hydroxycotinine/cotinine ratios	Assessed at screening visit
Secondary	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
Secondary	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
Secondary	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
Secondary	Respiratory symptoms	Yes/no: shortness of breath, wheezing, cough, phlegm	At baseline and 5 minutes after the last puff
Secondary	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
Secondary	Heart rate	Heart rate measurements (bpm)	15 minutes before and 2, 10, 15, 30, 60, 120, and 180 minutes after the last puff
Secondary	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
Secondary	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