Characterization of Nicotine Exposure and Urge-to-Smoke Following Use of Electronic and Conventional Cigarettes
Condition: Smoking
Study type: Interventional

Summary: 
      This trial was the initial characterization of the blu™ products being studied, with the
      purpose of gaining an understanding of the exposure to nicotine and craving reduction
      attained following use of blu™ e-cigarettes by adult smokers. Two types of exposures were
      utilized: a single controlled administration and a short-term ad lib use. As smoking
      behaviors vary from smoker to smoker, a controlled administration allows for some
      standardization of nicotine "dose" for each of the study products to better understand their
      uptake characteristics as well as urge reduction achieved under controlled conditions.
      Further evaluation under ad lib product use conditions provides insight into product
      self-administration behaviors that will allow subjects to achieve acceptable levels of urge
      reduction. Comparisons were made to evaluate differences between blu™ formulations as well as
      to the market-leading conventional cigarette, Marlboro Gold King Size ("Marlboro cigarette').
    

Detailed description: 
      This was a randomized, partially single-blinded, 6-period crossover study of 24 subjects.

      The primary objectives of this study were to:

        1. characterize the rate and extent of nicotine exposure following a single controlled
           administration and ad lib use of blu™ e-cigarettes,

        2. characterize smoking urge following a single controlled administration and ad lib use of
           blu™ e cigarettes.

      The secondary objectives of this study were to:

        1. Compare the pharmacokinetic (PK) profile of nicotine between selected blu™ formulations
           and between the blu™ products and Marlboro cigarettes following a single controlled
           administration and ad lib use of each study product.

        2. Compare changes in smoking urge within and between selected blu™ formulations and
           between the blu™ products and Marlboro cigarettes following a single controlled
           administration and ad lib use of each study product.

        3. Compare the changes in exhaled carbon monoxide (CO) within and between selected blu™
           formulations and between the blu™ products and Marlboro cigarettes following use of each
           study product.

        4. Assess the tolerability of each study product following short-term use.

      Subjects were provided blu™ Classic Tobacco and Magnificent Menthol products containing 2.4%
      nicotine, glycerin vehicle for 1 week prior to participation in the study to familiarize
      themselves with the use of the products. Subjects were confined to the clinic for the entire
      study duration and abstained from use of nicotine containing products for a period of at
      least 36 hours prior to each product administration. Each product administration included a
      controlled product administration and a 1 hour ad lib use of the study products. The
      controlled product administration consisted of 50 inhalations of the assigned e-cigarette
      product (5-second inhalations at 30-second intervals) or smoking one Marlboro cigarette
      (30-second intervals with the subjects' normal inhalation duration) with inhalations
      monitored by the clinical staff. The start of the ad lib product use was 30 minutes following
      the start of the controlled product use. During ad lib use, subjects were allowed to
      self-administer the e-cigarette product as desired for the entire hour and were responsible
      for maintaining their own inhalation counts. During the ad lib cigarette product use,
      subjects requested the product from the staff as desired and maintained their own inhalation
      counts.

      Pharmacokinetics: Blood samples for the measurement of plasma nicotine concentrations were
      taken by direct venipuncture at 10 minutes prior to, and 5, 10, 15, 20, 25, 30, 45, 60, 75,
      and 90 minutes following the start of the controlled product administration.
      Non-compartmental PK parameters such as Peak Plasma Concentration and Area under the Plasma
      Concentration versus time curve were calculated from the plasma nicotine concentration-time
      data.

      Pharmacodynamics: Smoking urge was assessed using a 100 mm visual analog scale (VAS).
      Assessments occurred within 1 minute prior to the -10 (pre-product administration), 5, 15,
      25, 30, 60, and 90-minute PK blood draws. The following non-compartmental Pharmacodynamic
      parameters were calculated from the smoking urge change-from-baseline data: Emax0-30,
      Emaxreduction0-30, AUEC0-30, tEmax0-30, AUEC30-90, and E90.

      Other Measurements: Exhaled CO measurements occurred at approximately 20 minutes prior to the
      start of the controlled product use and at approximately 15 minutes following the end of the
      ad lib product use.

      Tolerability: Adverse events, physical examinations, vital signs, ECGs, and laboratory safety
      tests were assessed to evaluate enrolment criteria and subject safety during the study.
    

Intervention name(s): blu™ Classic Tobacco rechargeable (2.4% nicotine, glycerin vehicle); blu™ Classic Tobacco rechargeable (2.4% nicotine, glycerin/PG vehicle); blu™ Magnificent Menthol rechargeable (2.4% nicotine, glycerin vehicle); blu™ Classic Tobacco rechargeable (1.6% nicotine, glycerin vehicle); blu™ Classic Tobacco rechargeable (1.6% nicotine, glycerin/PG vehicle); Marlboro Cigarette
Intervention type(s): Other; Other; Other; Other; Other; Other
Intervention description(s): electronic cigarettes; electronic cigarettes; electronic cigarettes; electronic cigarettes; electronic cigarettes; cigarettes
Intervention MeSH terms: Menthol; Nicotine; Glycerol
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Keywords: Nicotine; Pharmacokinetics; Pharmacodynamics; blu e-cigs; Tolerability; Safety; Smoke urge