Part Two: Pharmacokinetic Evaluation of E-Liquid Flavors of Vuse Solo Electronic Nicotine Delivery System, An Unblinded, Parallel, Randomized Study To Assess Nicotine Uptake In Smokers

Abstract

This paper reports the findings of a randomized nicotine pharmacokinetic (PK) study of a closed electronic nicotine delivery system (ENDS). The study evaluated four flavor variants of Vuse Solo ENDS where subjects used their randomized investigational product (IP) for 10 minutes ad libitum and blood samples were collected for PK assessments that included maximum plasma nicotine concentration (Cmax) and area under the nicotine concentration-vs-time curve up to 60 minutes (AUCnic0–60). Baseline-adjusted mean Cmax ranged from 6.53 to 8.21 ng/mL, and mean AUCnic0–60 ranged from 206.87 to 263.52 ng*min/mL for all ENDS IPs. Results for Cmax and AUCnic0-60 values were consistent among the ENDS IP flavor variants tested and results indicate that flavors did not affect nicotine uptake in human subjects.

Part three: a randomized study to assess biomarker changes in cigarette smokers switched to Vuse Solo or Abstinence

“…Across this study and the other two reported as part of this series, 53 total AEs were reported by 68 subjects using Vuse Solo 34,35 . Of these, the study PI determined 11 AEs were possibly related and 9 AEs were related to Vuse Solo use (Supplementary Table S3).…”

Part one: abuse liability of Vuse Solo (G2) electronic nicotine delivery system relative to combustible cigarettes and nicotine gum

“…A range of C max values has been reported in other published studies of Vuse Solo. For example, Hong et al (2022) report a mean C max of 6.91 ng/ml (Vuse Solo G2) after 10-min ad libitum product use among a population of exclusive smokers and dual users of cigarettes and ENDS 39 . In another study, a small sample of experienced ENDS users achieved relatively high nicotine uptake after five minutes of ad libitum Vuse Solo use (mean C max of 13.6 ng/ml) 11 .…”

“…Such results hold true in other studies of ENDS, despite differences in product design and variability in individual nicotine uptake 44,51,52 . Furthermore, across all studies of Vuse Solo, the observed differences in product liking scores between the Vuse Solo products (Vuse Solo G1 [Original, Menthol] and Vuse Solo G2 [Original, Menthol, and other flavors]) did not translate to substantial differences in nicotine PK parameters during acute ad libitum use 22,23,39 .…”

“…A tenminute "unit of use" for ENDS products was previously used by RAIS in similar studies (Stiles et 22,23,59,60 . Therefore, the same 10-min time frame of Vuse Solo product use was employed in this study and in Hong et al (Part 2 in this series) to allow for comparison across studies 39 . Lastly, because the commercial Vuse Solo e-liquids are manufactured with only one nicotine concentration, only one concentration was assessed in this study.…”

“…One explanation for this may be the limited time with which subjects interacted with the Vuse product (seven 10-min uses) versus nicotine gum (seven 30-min uses) and their usual brand cigarette (multiple periods of ad libitum use). However, in the companion PK study with similar product use parameters, two AEs (oropharyngeal pain and gastroesophageal reflux) were identified as related or possibly related to Vuse Solo use 39 . Furthermore, AEs related to Vuse Solo use in short-term switching studies have been reported and commonly include headache, nausea, and cough 38,40 .…”