Pharmacokinetics and Pharmacodynamics of Synthetic Nicotine and Nicotine Analogues

NCT07348224 | Not Yet Recruiting DMC

• 1 other identifier: BASEC-ID 2025-01893
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Electronic cigarettes are battery-operated devices that can produce an aerosol by heating a liquid which commonly contains nicotine. In recent years, products containing synthetically produced nicotine and nicotine analogues have entered the market. However, it remains unclear whether these types of nicotine have the same effects as conventional nicotine derived from the tobacco plant. The aim of this study is to investigate the effects of these nicotine types and to gain a better understanding of their respective mechanisms of action.

Conditions

Nicotine; Vaping; Synthetic Nicotine; Nicotine Analogues

Keywords

synthetic nicotine; nicotine analogues; vaping

Outcome Measures

Primary Outcomes (1)

• Maximum total nicotine concentrations (Cmax)

  Comparison of the maximum total nicotine (i.e. sum of both enantiomers) in blood concentrations (Cmax) between groups

  15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff

Secondary Outcomes (26)

• Maximum concentration (Cmax) of 6-methylnicotine

  15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff

• Maximum concentration (Cmax) of 6-methylnicotine's metabolites

  15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff

• AUC (area under the concentration-time curve) nicotine enantiomers

  15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff

• AUC (area under the concentration-time curve) 6-methylnicotine

  15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff

• AUC (area under the concentration-time curve) 6-methylnicotine's metabolites

  15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff

Other Outcomes (1)

• Reported adverse events

  Throughout study completion, an average of 2.5-6.5 weeks

Study Arms (3)

Synthetic S-Nicotine

OTHER

Vaping of e-liquids contanining synthetic S-nicotine

Other: Vaping of synthetic S-nicotine

Racemic nicotine (S-/R-nicotine)

OTHER

Vaping of e-liquids contanining synthetic racemic nicotine (containing both the S- and R-nicotine enantiomers)

Other: Vaping of racemic nicotine (S-/R-nicotine)

6-methylnicotine

OTHER

Vaping of e-liquids contanining the nicotine analogue 6-methylnicotine (6MN)

Other: Vaping of 6-methylnicotine

Interventions

Vaping of synthetic S-nicotine OTHER

Vaping of e-liquids containing synthetic S-nicotine

Synthetic S-Nicotine

Vaping of 6-methylnicotine OTHER

Vaping of e-liquids containing the nicotine analogue 6-methylnicotine (6MN)

6-methylnicotine

Vaping of racemic nicotine (S-/R-nicotine) OTHER

Vaping of e-liquids containing synthetic racemic nicotine (S-/R-nicotine)

Racemic nicotine (S-/R-nicotine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women, age 18 or older at screening who have used EC with nicotine during at least 10 of the past 30 days
• Saliva cotinine concentration of \> 30 ng/mL 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 engaging in sexual activities which can lead to pregnancy: willingness of using a reliable/hormonal contraception method during the study (hormonal, e.g. pill, intrauterine devices, or mechanical method, e.g. condom, diaphragm)
• Signed informed consent form

You may not qualify if:

• Known hypersensitivity/allergy to a content of the e-liquids
• Smoking of more than 5 cigarettes per day in the past 30 days
• Pregnant or lactating women
• Intention to become pregnant during the course of the study
• BMI \< 18 or \> 30 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 medications with known 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 of 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

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Swiss Tobacco Prevention Funds: collaborator

Study Sites (1)

Inselspital

Bern, Switzerland

Location

MeSH Terms

Conditions

Vaping

Condition Hierarchy (Ancestors)

Smoking; Behavior

Central Study Contacts

Evangelia Liakoni, Prof.

CONTACT

+41 31 632 54 61; evangelia.liakoni@insel.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2025
• First Posted: January 16, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-04

Locations

CH (1)