Characterization of Biomarkers of Tobacco Exposure, Urge-to-Smoke Following Exclusive and Dual Ad Lib Use of Electronic Cigarettes
Condition: Cigarette Smoking
Study type: Interventional

Summary: 
      This is a randomized, open-label, forced-switch, parallel, proof-of-concept study to assess
      exposure to biomarkers of tobacco exposure following short-term ad lib use of three blu
      e-cigarette products. The primary objectives of this study are to:

        1. Compare changes in selected urine and blood biomarkers of tobacco exposure within
           cohorts following a 5-day forced-switch from usual brand conventional combustible
           cigarettes to exclusive use of blu e-cigarettes, dual use of blu e cigarettes and the
           subject's usual brand combustible cigarette, or smoking cessation.

        2. Compare changes in selected urine and blood biomarkers of tobacco exposure among cohorts
           following a 5-day forced-switch from usual brand conventional combustible cigarettes to
           exclusive use of a blu e cigarette, dual use of a blu e-cigarette and the subject's
           usual brand combustible cigarette, or smoking cessation.

      The secondary objectives of this study are to:

        1. Compare changes in selected physiological endpoints affected by tobacco exposure within
           cohorts during a 5-day forced-switch from usual brand conventional combustible
           cigarettes to exclusive use of blu e cigarettes, dual use of blu e cigarettes and the
           subject's usual brand combustible cigarette, or smoking cessation.

        2. Compare changes in selected physiological endpoints affected by tobacco exposure among
           cohorts following a forced-switch to exclusive use of a blu e cigarette, dual use of a
           blu e-cigarette and the subject's usual brand combustible cigarette, or smoking
           cessation.

        3. Determine daily nicotine consumption from blu e-cigarettes following exclusive use of
           blu e cigarettes or dual use of blu e-cigarettes and the subject's usual brand
           combustible cigarette over a 5-day period.

        4. Assess the effectiveness of exclusive use of blu e-cigarettes or dual use of blu
           e-cigarettes and the subject's usual brand combustible cigarette to reduce the urge to
           smoke.

        5. Assess subject opinions of various characteristics of blu e-cigarettes.

        6. Assess the safety and tolerability of short-term use of blu e-cigarettes.
    

Detailed description: 
      Subjects checked in to the clinic on Day -2 and continued to smoke their usual brand
      cigarette ad lib through the evening of Day -1 upon request to the clinic staff. Baseline
      assessments were made from the morning of Day -1 through the morning of Day 1 prior to the
      start of randomized product use. On the morning of Day 1, subjects were randomized into one
      of the study arms noted above and post-baseline assessments were made through the morning of
      Day 6.

      With limited exceptions, all product use was ad lib from 07:30 to 23:00 on Days -2 to 5.
      Smoking of cigarettes and use of the e-cigarette products were limited to separate sections
      of the clinic to minimize the chance for illicit product use and cross-contamination.
      Subjects randomized to the cessation arm were housed in a separate section of the clinic
      after randomization.

      From Day 1 to the end of the study all subjects randomized to an e-cigarette cohort were
      allowed to carry the assigned product with them throughout the day and use their product ad
      lib within identified sections of the clinic. Subjects randomized to the dual-use cohorts
      were allowed to smoke no more than 50% of the number of cigarettes per day reported at
      Screening. Cigarettes were were provided to the subjects upon request to the study staff.

      Daily product use of blu e-cigarettes and usual brand cigarettes was assessed on Days -1
      through Day 5. Each blu e-cigarette was weighed prior to dispensing and following the return
      of the product and the estimated amount of nicotine delivered from each blu e-cigarette will
      be calculated by multiplying the weight difference (mg) by 2.4%.

      Urine biomarkers of exposure and effect were assessed from 24-hour urine collections from the
      morning of Day -1 to the morning of Day 1 and from the morning of Day 5 to the morning of Day
      6. Urine biomarkers of exposure included NNAL, nicotine equivalents (nic + 5), 3-HPMA, CEMA,
      1-OHP, NNN, MHBMA, and S-PMA. The urine biomarker of effect included F2-isoprostane
      (8-iso-PGF2 Type III). Biomarker concentrations were adjusted for urine creatinine
      concentrations.

      Blood biomarkers of exposure included COHb, nicotine, cotinine, and trans-3'hydroxycotinine.
      Samples were collected on Days -1, 1, 3, and 5 in the morning prior to the start of product
      administration and in the evening.

      Other physiologic endpoints included spirometry (FVC and FEV1, assessed in the afternoon on
      Day -1 and Day 5, exhaled CO and NO measurements (assessed in the afternoon on Days -1, 1, 3,
      and 5), and blood pressure and pulse rate (assessed on Days -1 through 5 in the morning prior
      to the start of product administration and evening).

      Questionnaires administered included the Fagerström Test for Nicotine Dependence and the
      Brief Wisconsin Inventory of Smoking Dependence Motives (Day -1), smoking urge (Days -1
      through 5 in the morning prior to the start of product administration and evening), and the
      Modified Cigarette Evaluation Scale (evening of Day 5, not administered to subjects in the
      cessation arm).

      Safety evaluations included physical examinations, vital signs, ECGs, clinical laboratory
      assessments (clinical chemistry, hematology, urinalysis, and serology), urine drug and
      alcohol screens, urine cotinine and exhaled CO screens, and pregnancy tests (females only).
      Adverse events spontaneously reported by the subjects or observed by the Investigator or
      other study personnel were monitored from the time of Check-in until the End-of-Study (or
      Early Termination). Any concomitant medications taken from 30 days prior to Check-in through
      the End-of-Study (or Early Termination) were recorded.
    

Intervention name(s): Exclusive blu™ e-cigarette A1; Exclusive blu™ e-cigarette A2; Exclusive blu™ e-cigarette A3; Dual blu™ e-cigarette and usual brand B1; Dual blu™ e-cigarette and usual brand B2; Dual blu™ e-cigarette and usual brand B3; Nicotine product cessation C
Intervention type(s): Other; Other; Other; Other; Other; Other; Other
Intervention description(s): Classic Tobacco rechargeable e cigarette; Magnificent Menthol rechargeable e cigarette; Cherry Crush rechargeable e cigarette; Classic Tobacco rechargeable e cigarette and a usual brand combustible cigarette; Magnificent Menthol rechargeable e cigarette and a usual brand combustible cigarette; Cherry Crush rechargeable e cigarette and a usual brand combustible cigarette; Nicotine cessation
Intervention MeSH terms: Nicotine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science