Clinical trial NCT04170907: Pharmacokinetics and Pharmacodynamics of Different Nicotine Salt Concentration Vape System Pods and Free-base Nicotine
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nicotine Dependence
Keywords: nicotine
pharmacokinetics
pharmacodynamics
Lead sponsor: Insel Gruppe AG, University Hospital Bern
Sponsor class: OTHER
Collaborators: name: University of Bern
First posted: 2019-11-20
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Participants will be switched in a within-subject crossover design among the three product types.
Primary purpose: OTHER

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Nicotine Peak Plasma Concentration (Cmax)
timeFrame: Blood samples collection: 15 minutes before and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
Secondary outcomes:
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: Blood samples collection: 15 minutes before and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
measure: Time at which the Cmax is observed (Tmax)
timeFrame: Blood samples collection: 15 minutes before and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
measure: Elimination half-life (t1/2)
timeFrame: Blood samples collection: 15 minutes before and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
measure: Genotyping of the hepatic cytochrome P450 enzyme CYP2A6
timeFrame: Blood sample collection during first session
measure: Nicotine metabolite ratio (NMR)
timeFrame: Assessed at screening visit
measure: Modified Minnesota Nicotine Withdrawal Scale (MNWS)
timeFrame: Baseline, 10 minutes and 1 and 3 hours after the last puff
measure: Tiffany Questionnaire on Smoking Urges-Brief (QSU) total (global) craving score
timeFrame: Baseline, 10 minutes and 1 and 3 hours after the last puff
measure: Positive and Negative Affect Schedule (PANAS)
timeFrame: Baseline, 10 minutes and 1 and 3 hours after the last puff
measure: Respiratory symptoms
timeFrame: At baseline and 5 minutes after the last puff
measure: Direct effects
timeFrame: Ten minutes post-use
measure: Heart rate
timeFrame: 15 minutes before and 2, 10, 15, 30, 60, 120, and 180 minutes after the last puff
measure: Systolic blood pressure
timeFrame: 15 minutes before and 2, 10, 15, 30, 60, 120, and 180 minutes after the last puff
measure: Diastolic blood pressure
timeFrame: 15 minutes before and 2, 10, 15, 30, 60, 120, and 180 minutes after the last puff
Other outcomes:
Locations:
city: Bern
country: Switzerland
facility: Inselspital, University Hospital Bern
state: BE
Study officials:
affiliation: Sponsor: Inselspital, Bern University Hospital
name: Evangelia Liakoni, MD
role: PRINCIPAL_INVESTIGATOR
References: