Nicotine Pharmacokinetics From Research Electronic Nicotine Delivery System S-TA-U001 in Smokers and E-Cigarette Users

Cigarette Smoking Clinical Trial

Official title: A Study to Evaluate the Comparative Pharmacokinetics of Nicotine After Administration Via Research Electronic Nicotine Delivery System S-TA-U001 in Healthy Volunteer Smokers and Current E-Cigarette Users

Status Completed

Clinical Trial 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.

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Cigarette Smoking

• NCT number: NCT02792426
• Study type: Interventional
• Source: NJOY, Inc.
• Status: Completed
• Phase: Phase 1
• Start date: October 5, 2016
• Completion date: June 1, 2017