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

Abstract

Biomarkers of exposure (BoE) can help evaluate exposure to combustion-related, tobacco-specific toxicants after smokers switch from cigarettes to potentially less-harmful products like electronic nicotine delivery systems (ENDS). This paper reports data for one (Vuse Solo Original) of three products evaluated in a randomized, controlled, confinement study of BoE in smokers switched to ENDS. Subjects smoked their usual brand cigarette ad libitum for two days, then were randomized to one of three ENDS for a 7-day ad libitum use period, or to smoking abstinence. Thirteen BoE were assessed at baseline and Day 5, and percent change in mean values for each BoE was calculated. Biomarkers of potential harm (BoPH) linked to oxidative stress, platelet activation, and inflammation were also assessed. Levels decreased among subjects randomized to Vuse Solo versus Abstinence, respectively, for the following BoE: 42–96% versus 52–97% (non-nicotine constituents); 51% versus 55% (blood carboxyhemoglobin); and 29% versus 96% (nicotine exposure). Significant decreases were observed in three BoPH: leukotriene E4, 11-dehydro-thromboxane B2, and 2,3-dinor thromboxane B2 on Day 7 in the Vuse Solo and Abstinence groups. These findings show that ENDS use results in substantially reduced exposure to toxicants compared to smoking, which may lead to reduced biological effects.

Biomarkers of Exposure and Potential Harm in Two Weeks of Smoking Abstinence: Changes in Biomarkers of Platelet Function, Oxidative Stress, and Inflammation

“…The short-lived TXA 2 is metabolized to 2,3-d-TXB 2 and 11-dh-TXB 2 , which are routinely measured in urine as measures of platelet activation. The declines in 2,3-d-TXB 2 levels in 7 and 14 days are consistent with the findings from our previous work, which showed similar rapid declines following smoking abstinence or switching to ENDS products [ 21 , 22 ]. Several studies have reported that levels of 11-dh-TXB 2 are also higher in smokers compared to non-smokers (including moist snuff users) [ 12 , 13 , 14 ].…”

“…In an effort to identify BoPH that rapidly respond to smoking cessation and are mechanistically linked to the development of smoking-related diseases, RAI Services Company (RAIS) has identified two urinary eicosanoids, leukotriene E 4 (LTE 4 ) and 2,3-d-TXB 2 [ 14 ], and shown that the levels of eicosanoids rapidly decline upon smoking cessation or switching to non-combustible tobacco products [ 21 , 22 ]. With an objective to further qualify LTE 4 and 2,3-d-TXB 2 , we conducted a two-week biomarker study under clinical confinement, which we refer to as the Smoking Abstinence (SAB) study.…”

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

“…The significance threshold for secondary endpoints was 0.05. Forty (40) subjects were initially randomized in order to ensure that 30 subjects completed all test sessions.…”

“…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 . Reports of higher number of AEs during use of NRT gum relative to other products are not uncommon in studies with exclusive smokers, which may suggest that they are not familiar with sensations of oral product use 22 .…”

“…Part Two describes the PK of Vuse Solo G2 across four e-liquid flavors 39 . Part Three presents the results of a study to assess whether use of Vuse Solo G2 results in a reduction in exposure to harmful and potentially harmful constituents (HPHCs) after smokers are switched to the product for 5 days 40 . All studies reported in this three-part series were conducted to provide the FDA with evidence that Vuse Solo G2 is appropriate for the protection of the public health.…”