an Open-Label, Randomized, Controlled, Crossover Study to assess Nicotine Pharmacokinetics and Subjective Effects of the JUUL System with Three Nicotine Concentrations Relative to Combustible Cigarettes in adult Smokers.

Introduction:
This text provides an analysis of a clinical laboratory study that assessed nicotine pharmacokinetics (PK) and subjective effects of the Juul System (JS) with three nicotine concentrations and two different wicking materials in comparison to subjects' usual brand cigarettes. The study aims to evaluate the nicotine PK and subjective effects of JS with nicotine concentrations below the 20 mg/mL limit set by the European Union's Revision of the Tobacco Products Directive (EU TPD).

Key Points:

* The study enrolled 25 subjects, 20 males and 5 females, who were all of the white race and not hispanic or Latino ethnicity.
* Subjects were current smokers of at least 10 manufactured, non-mentholated cigarettes a day and had been smoking for at least 12 months.
* The four JS products used in the study had nicotine concentrations of 59, 18, and 9 mg/mL, and ph ranging from 5.9 to 6.2.
* The study design was a randomized, open-label, crossover study, conducted in accordance with the principles of the International Conference on harmonisation harmonised Tripartite Guideline for Good Clinical Practice and the Declaration of helsinki.
* Nicotine PK assessments were performed for the controlled puffing sequence (CPS) and ad libitum sessions, with 4 mL venous blood samples collected at specified timepoints.
* Subjective effects assessments were performed using a 20-item modified Product Evaluation Scale (mPES) after the collection of the 30-minute blood sample in the CPS session.
* Safety and tolerability were assessed via incidence and nature of adverse events (aEs) by the study investigator.

Main Message:
The study found that nicotine exposure from all JS was significantly less than that of UB cigarettes, and nicotine delivery from JS was nicotine concentration-dependent. The use of JS 59 mg/mL resulted in subjective relief from cravings that did not differ significantly from that of UB cigarettes, while JS 18 mg/mL and 9 mg/mL were rated significantly lower. The lower nicotine delivery and subjective relief from JS 18 and 9 mg/mL may not be sufficient to help all smokers, particularly heavier and more dependent smokers, transition away from cigarettes. The study suggests that the lower nicotine delivery and subjective relief from JS 18 and 9 mg/mL may not be effective substitutes for cigarettes, and heavier and more dependent smokers may require ENDS with nicotine concentrations greater than 20 mg/mL to successfully transition away from cigarettes.

Goldenson NI, Fearon IM, Buchhalter aR, henningfield JE. an Open-Label, Randomized, Controlled, Crossover Study to assess Nicotine Pharmacokinetics and Subjective Effects of the JUUL System with Three Nicotine Concentrations Relative to Combustible Cigarettes in adult Smokers. Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco. 2021;23(6):947-955. doi:10.1093/ntr/ntab001