Smoking
Conditions
Keywords
Conventional cigarette, Nicotine lactate delivery system, e-cigarette, VUSE, Combustible cigarette
Brief summary
This study will provide an initial assessment of the acceptability of the Nicotine Lactate Delivery System (P3L) after ad libitum use and the ability of combustible cigarette (CC) smokers to use P3L to maintain their customary nicotine intake, in a manner comparable with their own brand of CC or the VUSE e-cigarette system.
Detailed description
The total duration of the study for an individual subject will be between 3 and 8 weeks, including 1 day for the screening visit, 3 days for the ad libitum use sessions (P3L, VUSE e-cigarette system and subjects' own commercially available non-menthol CC), 1 day for the preference evaluation session (subjects will be given the choice of using ad libitum the P3L or the VUSE), the 2 to 10 days of interval between each visit, and 7 days for the passive safety follow-up period. The pharmacokinetics (PK) and pharmacodynamics (PD, i.e., subjective effects) profiles, will be evaluated as well as the safety and tolerability of the P3L.
Interventions
OTHERP3L
Ad libitum use for a maximum of three hours. P3L delivers, on average, 80 µg of nicotine per puff under Health Canada Intense smoking regime.
OTHERVUSE
Ad libitum use for a maximum of three hours. VUSE delivers, on average, 80 µg of nicotine per puff based on the CORESTA e-cigarette recommended smoking regime.
OTHERCC
Ad libitum use of the subject's own brand of non-menthol CC for a maximum of three hours.
Sponsors
Philip Morris Products S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Smoking, healthy subject as judged by the Investigator * Subject smoked at least 10 commercially available non-menthol CCs per day for the last 12 months * Subject does not plan to quit smoking in the next 60 days
Exclusion criteria
* As per Investigator judgment, the subject cannot participate in the study for any reason (e.g., medical, psychiatric, and/or social reason) * Subject has donated or been in receipt of whole blood or blood products within 3 months prior to the screening visit * Subject has used tobacco products or nicotine containing products other than CCs within 30 days prior to the screening visit * Female subject is pregnant or breast feeding * Female subject does not agree to use an acceptable method of effective contraception * Female subject uses estrogen-containing hormonal contraception or hormone replacement therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Plasma Concentration of Nicotine/Cotinine After Each ad Libitum Use Session. | Measured at 15 minutes and 5 minutes prior to each 3 hour product use to provide baseline measures, then at 15 minutes and 30 minutes after product use period to show change from baseline. | For each ad libitum use session (P3L, VUSE, and CC), change from baseline plasma concentration of Nicotine/Cotinine was measured from two blood samples collected before product use (to provide baseline measures) and from two blood samples collected following product use (to show change from baseline). |
| Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | QSU-brief questionnaire completed before product use session, then at 60 mins, 120 mins, and 180 mins after starting each product use session. | The QSU-Brief questionnaire is an instrument used to measure urge to smoke. Subjects were asked to respond to 10 questions, scored from 1 to 7 on a 7-point scale. A score of 1 on this scale indicates a very low urge to smoke, while a score of 7 indicates a very high urge to smoke. Subjects were asked to complete the questionnaire before, during, and after each ad libitum product use session. (P3L, VUSE, and Subjects' Own Brand of Non-menthol CC). Two factor scores and a total score were derived. Factor 1 represents the desire and intention to smoke with smoking perceived as rewarding, while Factor 2 represents an anticipation of relief from negative effect with an urgent desire to smoke. Products were compared over all timepoints using a repeated measure model using values after t0. The model adjusted for baseline value, sequence, and period with repeated measure over time and a random effect in subjects. Adjusted mean over all timepoints, for each timepoint, were estimated. |
Countries
United States
Participant flow
Recruitment details
Study initiated (1st subject screened): 16 November 2015 A demonstration of the P3L system and the VUSE e-cigarette system was given to the subjects.
Pre-assignment details
Enrolled population = 24 subjects All enrolled subjects met all of the inclusion and none of the exclusion criteria for the study. Subject product use was randomly assigned for each ad libitum use session, following a sequence of product exposure comprised of the three products (P3L, VUSE, and CC).
Participants by arm
| Arm | Count |
|---|---|
| P3L/VUSE/CC Product Exposure Subject product use was randomly assigned for each ad libitum use session, following a sequence of product exposure comprised of the three products (P3L, VUSE, and CC). | 22 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Adherence Issues | 2 | 0 | 1 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | P3L/VUSE/CC Product Exposure |
|---|---|
| Age, Customized <=19 years | 0 Participants |
| Age, Customized >=65 years | 0 Participants |
| Age, Customized Between 19 and 65 years | 22 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 19 | 0 / 19 |
| other Total, other adverse events | 14 / 21 | 13 / 19 | 9 / 19 |
| serious Total, serious adverse events | 0 / 21 | 0 / 19 | 0 / 19 |
Outcome results
Primary
Change From Baseline Plasma Concentration of Nicotine/Cotinine After Each ad Libitum Use Session.
For each ad libitum use session (P3L, VUSE, and CC), change from baseline plasma concentration of Nicotine/Cotinine was measured from two blood samples collected before product use (to provide baseline measures) and from two blood samples collected following product use (to show change from baseline).
Time frame: Measured at 15 minutes and 5 minutes prior to each 3 hour product use to provide baseline measures, then at 15 minutes and 30 minutes after product use period to show change from baseline.
Population: All the subjects who gave informed consent and completed all three ad libitum use sessions, without major protocol deviations.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| P3L Product Exposure | Change From Baseline Plasma Concentration of Nicotine/Cotinine After Each ad Libitum Use Session. | Baseline (Average) before session: Nicotine | 1.7621 (ng/mL) |
| P3L Product Exposure | Change From Baseline Plasma Concentration of Nicotine/Cotinine After Each ad Libitum Use Session. | Change from Baseline after session: Nicotine | 5.5571 (ng/mL) |
| P3L Product Exposure | Change From Baseline Plasma Concentration of Nicotine/Cotinine After Each ad Libitum Use Session. | Baseline (Average) before session: Cotinine | 182.554 (ng/mL) |
| P3L Product Exposure | Change From Baseline Plasma Concentration of Nicotine/Cotinine After Each ad Libitum Use Session. | Change from Baseline after session: Cotinine | 15.222 (ng/mL) |
| VUSE Product Exposure | Change From Baseline Plasma Concentration of Nicotine/Cotinine After Each ad Libitum Use Session. | Change from Baseline after session: Cotinine | 11.163 (ng/mL) |
| VUSE Product Exposure | Change From Baseline Plasma Concentration of Nicotine/Cotinine After Each ad Libitum Use Session. | Baseline (Average) before session: Nicotine | 2.4113 (ng/mL) |
| VUSE Product Exposure | Change From Baseline Plasma Concentration of Nicotine/Cotinine After Each ad Libitum Use Session. | Baseline (Average) before session: Cotinine | 187.559 (ng/mL) |
| VUSE Product Exposure | Change From Baseline Plasma Concentration of Nicotine/Cotinine After Each ad Libitum Use Session. | Change from Baseline after session: Nicotine | 7.3425 (ng/mL) |
| CC Product Exposure | Change From Baseline Plasma Concentration of Nicotine/Cotinine After Each ad Libitum Use Session. | Change from Baseline after session: Cotinine | 33.888 (ng/mL) |
| CC Product Exposure | Change From Baseline Plasma Concentration of Nicotine/Cotinine After Each ad Libitum Use Session. | Change from Baseline after session: Nicotine | 17.1821 (ng/mL) |
| CC Product Exposure | Change From Baseline Plasma Concentration of Nicotine/Cotinine After Each ad Libitum Use Session. | Baseline (Average) before session: Cotinine | 199.547 (ng/mL) |
| CC Product Exposure | Change From Baseline Plasma Concentration of Nicotine/Cotinine After Each ad Libitum Use Session. | Baseline (Average) before session: Nicotine | 1.9446 (ng/mL) |
Primary
Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief)
The QSU-Brief questionnaire is an instrument used to measure urge to smoke. Subjects were asked to respond to 10 questions, scored from 1 to 7 on a 7-point scale. A score of 1 on this scale indicates a very low urge to smoke, while a score of 7 indicates a very high urge to smoke. Subjects were asked to complete the questionnaire before, during, and after each ad libitum product use session. (P3L, VUSE, and Subjects' Own Brand of Non-menthol CC). Two factor scores and a total score were derived. Factor 1 represents the desire and intention to smoke with smoking perceived as rewarding, while Factor 2 represents an anticipation of relief from negative effect with an urgent desire to smoke. Products were compared over all timepoints using a repeated measure model using values after t0. The model adjusted for baseline value, sequence, and period with repeated measure over time and a random effect in subjects. Adjusted mean over all timepoints, for each timepoint, were estimated.
Time frame: QSU-brief questionnaire completed before product use session, then at 60 mins, 120 mins, and 180 mins after starting each product use session.
Population: All the subjects who gave informed consent and completed all three ad libitum use sessions, without major protocol deviations.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| P3L Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Total Score - Over all timepoints | 3.86 score on a scale |
| P3L Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 2 - Over all timepoints | 2.85 score on a scale |
| P3L Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 2 - t0 + 120mins | 2.84 score on a scale |
| P3L Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Total Score - t0 + 60mins | 4.02 score on a scale |
| P3L Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Total Score - t0 + 120mins | 3.84 score on a scale |
| P3L Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Total Score - t0 + 180mins | 3.71 score on a scale |
| P3L Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 1 - Over all timepoints | 4.97 score on a scale |
| P3L Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 1 - t0 + 60mins | 4.87 score on a scale |
| P3L Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 1 - t0 + 120mins | 4.99 score on a scale |
| P3L Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 1 - t0 + 180mins | 5.05 score on a scale |
| P3L Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 2 - t0 + 60mins | 2.95 score on a scale |
| P3L Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 2 - t0 + 180mins | 2.76 score on a scale |
| VUSE Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Total Score - t0 + 120mins | 3.07 score on a scale |
| VUSE Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Total Score - t0 + 60mins | 3.24 score on a scale |
| VUSE Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 1 - Over all timepoints | 4.11 score on a scale |
| VUSE Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 2 - t0 + 180mins | 2.06 score on a scale |
| VUSE Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Total Score - t0 + 180mins | 2.94 score on a scale |
| VUSE Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 1 - t0 + 120mins | 4.11 score on a scale |
| VUSE Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 2 - Over all timepoints | 2.15 score on a scale |
| VUSE Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 2 - t0 + 60mins | 2.25 score on a scale |
| VUSE Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 2 - t0 + 120mins | 2.14 score on a scale |
| VUSE Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 1 - t0 + 60mins | 4.48 score on a scale |
| VUSE Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 1 - t0 + 180mins | 3.74 score on a scale |
| VUSE Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Total Score - Over all timepoints | 3.08 score on a scale |
| CC Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 2 - t0 + 120mins | 1.59 score on a scale |
| CC Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Total Score - t0 + 60mins | 2.09 score on a scale |
| CC Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Total Score - t0 + 120mins | 1.91 score on a scale |
| CC Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Total Score - t0 + 180mins | 1.78 score on a scale |
| CC Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 1 - t0 + 180mins | 1.84 score on a scale |
| CC Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Total Score - Over all timepoints | 1.93 score on a scale |
| CC Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 1 - Over all timepoints | 2.15 score on a scale |
| CC Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 1 - t0 + 60mins | 2.53 score on a scale |
| CC Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 1 - t0 + 120mins | 2.08 score on a scale |
| CC Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 2 - t0 + 180mins | 1.51 score on a scale |
| CC Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 2 - Over all timepoints | 1.60 score on a scale |
| CC Product Exposure | Overall Score of the Short Version of the Questionnaire of Smoking Urges (QSU-brief). Total Score; Factor 1 (Reward); Factor 2 (Relief) | Factor 2 - t0 + 60mins | 1.71 score on a scale |