Nicotine Pharmacokinetics From Research Electronic Nicotine Delivery System S-TA-U001 in Smokers and E-Cigarette Users
Condition: Cigarette Smoking
Study type: Interventional
Phase: Phase 1

Summary: 
      To better understand the PK and associated pharmacodynamic (PD) responses produced by the
      Research ENDS S-TA-U001 product, this study will compare the Research ENDS S-TA-U001 to

        -  The subject's own brand combustion (non-menthol) cigarette and a U.S. FDA approved
           smoking cessation product, the NICORETTE Inhalator, in current non-menthol cigarette
           smokers who have some limited e-cigarette experience (Group 1).

        -  Commercially available products in current primarily e-cigarette users (experienced ENDS
           users) (Group 2) The PK/PD session for each product will be conducted in a controlled
           clinical setting with frequent PK sampling after 14 hours of supervised abstinence from
           all forms of nicotine. Subjects will familiarize themselves with the Research ENDS
           S-TA-U001 and NICORETTE Inhalator by using each product in the real world for one day
           before the PK/PD session for that product.

      Primary Objectives:

      Group 1 objectives are to characterize the nicotine PK profile (eg, maximum plasma
      concentration [Cmax], time to maximum plasma concentration [Tmax], area under the
      concentration-time curve [AUC], and terminal half-life [t1/2]) for 10 inhalation and ad lib
      sessions of Research ENDS S-TA-U001 and explore how the Cmax compares to a 15 ng/mL level
      during the 4.5-minute 10 inhalation and the 6 hour ad lib use sessions, to compare the PK
      profiles between Research ENDS S-TA-U001 to the profiles of combustion cigarettes measured at
      the baseline session, and to demonstrate superiority of PK profile of Research ENDS S-TA-U001
      to that of the marketed NICORETTE Inhalator.

      Group 2 objectives are to characterize the nicotine PK profile of Research ENDS S-TA-U001 and
      explore how the Cmax compares to a 15 ng/mL level during the 4.5-minute 10 inhalation and 6
      hour ad lib use sessions, and to compare the PK profile between Research ENDS S-TA-U001 to
      the profile of a commercial ENDS product measured at the baseline session.

      Secondary objectives:

      Secondary objectives include comparison of the nicotine PK of the Research ENDS S-TA-U001 to
      the subjects' normal nicotine source (combustion cigarettes for Group 1 or commercial ENDS
      for Group 2), to evaluate the safety and tolerability of Research ENDS S-TA-U001, to evaluate
      the effects on craving and user satisfaction of the Research ENDS S-TA-U001 vs a combustion
      cigarette or the NICORETTE Inhalator (Group 1) or a commercial ENDS product (Group 2), and to
      evaluate various biomarkers following use of each test product.
    

Detailed description: 
      Subjects in Group 1 will participate in a Phase 1 2×2 cross-over study of the Research ENDS
      S-TA-U001 (Test Product A) and NICORETTE Inhalator (Test Product B). Subjects in Group 2 will
      participate in a study to examine the effect of the Research ENDS S-TA-U001 (Test Product A).

      Approximately 20 healthy volunteers, ages 21 to 65 inclusive, who are current combustion
      cigarette smokers will be enrolled into Group 1 for the 2×2 cross-over study. Approximately
      14 healthy volunteers, ages 21 to 65 inclusive, who are current primarily e cigarette users
      will be enrolled into Group 2. Initial screening for the study will occur from 7 to 21 days
      before the first PK assessment/in-clinic device Training Visit on Day 1. Subjects in Group 1
      will be randomized to Sequence AB (10 subjects) or Sequence BA (10 subjects).

      On Day 1, subjects will arrive at the research site to begin at least 14 hours of overnight
      supervision to insure abstinence from all forms of nicotine prior to the first administration
      of the Baseline Product. Each subject will complete a 10 inhalation session of his or her
      normal nicotine source (either the subject's own brand of a combustion cigarette [Group 1] or
      the subject's own brand of commercial ENDS product [Group 2]) in 4.5 minutes, abstain for 1
      hour 55 minutes, complete a second session of 10 inhalations in 4.5 minutes, complete a 6
      hour ad lib use session, and complete a series of behavioral assessments over the PK
      sampling/observation period lasting 8 hours and 5 minutes. The first series of 4.5-minute 10
      inhalation sessions will be videotaped to assess inhalation duration and technique. Subjects
      will abstain from food for one hour before each 10 puff session and caffeine within one hour
      of the first 10 puffs through the duration of the entire ad lib session.

      Following the sampling/observation period on Day 1, subjects in Group 1 Sequence AB and
      subjects in Group 2 will be trained on how to properly use the Research ENDS S-TA-U001, and
      Group 1 Sequence BA subjects will be trained on how to properly use the NICORETTE Inhalator.
      Prior to discharge, subjects will be provided with two cartridges of the Research ENDS
      S-TA-U001 or a set of NICORETTE Inhalator for at-home use for 1 day (starting immediately
      after clinic discharge) depending on the group and sequence to which they are assigned.
      Subjects will be encouraged (though not required) to use the Research ENDS S-TA-U001 or
      NICORETTE Inhalator as their exclusive nicotine source. Subjects will record the number of
      combustible cigarettes smoked (if any) and the number of cartridges of the Research ENDS
      S-TA-U001 or NICORETTE Inhalator used, depending on sequence (Group 1), or the number of
      cartridges of the Research ENDS S-TA-U001 used and the amount of e liquid used (if any) from
      their commercial ENDS products (Group 2). All subjects will be required to return all of the
      study devices used as well as used and unused cartridges at the next visit.

      On Day 3, subjects will arrive at the research site to begin at least 14 hours of overnight
      supervision to insure abstinence from all forms of nicotine prior to the first administration
      of the Test Product. Subjects in Group 1 Sequence AB and Group 2 will complete a 10
      inhalation session of Research ENDS S-TA-U001 in 4.5 minutes, abstain for 1 hour 55 minutes,
      complete a second session of 10 inhalations in 4.5 minutes, followed by a 6 hour ad lib use
      session. Subjects in Group 1 Sequence BA will complete a 10 inhalation session of NICORETTE
      Inhalator, abstain for 1 hour 55 minutes, complete a second session of 10 inhalations in 4.5
      minutes, followed by a 6 hour ad lib use session. A series of behavioral assessments will be
      performed during the PK sampling/observation period lasting 8 hours and 5 minutes. The first
      series of 4.5 minute 10 inhalation sessions for both products will be videotaped to assess
      inhalation duration and technique. Subjects will abstain from food for one hour before each
      10 puff session and caffeine within one hour of the first 10 puffs through the duration of
      the entire ad lib session. Subjects in Group 2 will be discharged from the clinic following
      the final PK blood draw and completion of all final clinical assessments on Study Day 3.
      Following the sampling/observation period, subjects in Group 1 Sequence AB will be trained on
      how to properly use the NICORETTE Inhalator and subjects in Group 1 Sequence BA will be
      trained on how to properly use the Research ENDS S-TA-U001. Prior to discharge, subjects,
      depending on the group and sequence to which they are assigned, will be provided with two
      cartridges of the Research ENDS S TA U001 or a set of NICORETTE Inhalator for at-home use for
      1 day (starting immediately after clinic discharge). Subjects will be encouraged (though not
      required) to use the Research ENDS S-TA-U001 or NICORETTE Inhalator as their exclusive
      nicotine source. All subjects will be required to return all of the study devices used as
      well as used and unused cartridges at the next visit.

      On Day 5, subjects in Group 1 will arrive at the research site to begin at least 14 hours of
      overnight supervision to insure abstinence from all forms of nicotine prior to the first
      administration of the Test Product. Subjects in Group 1 Sequence AB will complete a 10
      inhalation session of NICORETTE Inhalator in 4.5 minutes, abstain for 1 hour 55 minutes,
      complete a second session of 10 inhalations in 4.5 minutes, followed by a 6 hour ad lib use
      session. Subjects in Group 1 Sequence BA will complete a 10 inhalation session of Research
      ENDS S-TA-U001 in 4.5 minutes, abstain for 1 hour 55 minutes, complete a second session of 10
      inhalations in 4.5 minutes, followed by a 6-hour ad lib use session. A series of behavioral
      assessments will be performed during the PK sampling/observation period lasting 8 hours and 5
      minutes. The first series of 4.5 minute 10 inhalation sessions for both products will be
      videotaped to assess inhalation duration and technique. Subjects will abstain from food for
      one hour before each 10 puff session and caffeine within one hour of the first 10 puffs
      through the duration of the entire ad lib session. Subjects in Group 1 will be discharged
      from the clinic following the final PK blood draw and completion of all final clinical
      assessments on Study Day 5.
    

Intervention name(s): Research ENDS S-TA-U001; Nicorette Inhalator
Intervention type(s): Drug; Drug
Intervention MeSH terms: Nicotine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Smoking Cessation; Nicotine Dependence; Tobacco Dependence