Nicotine Vaping, Nicotine, Vaping
Conditions
Keywords
Nicotine, Pharmacokinetics, Smoking, Cigarette, E-Cigarette
Brief summary
This is a single-center, randomized, controlled, open-label, cross-over study with healthy adult smokers. The study will investigate the nicotine pharmacokinetic (PK) profiles of two e-liquid variants used with the P4M3 Gen 2.0 e-cigarette, compared to smoking combustible cigarettes. In addition, pharmacodynamic (PD) effects (subjective effects and related behavioral assessments), will be evaluated to provide further insights on product evaluation, craving, liking, puffing topography. The study will be conducted with three periods and six sequences in a cross-over design. This study is exploratory and there is no pre-specified hypothesis to be tested.
Detailed description
The purpose of the study is to evaluate the nicotine pharmacokinetics (PK) profiles of two e-liquid variants used with the P4M3 Gen 2.0 e-cigarette versus cigarettes following a six minutes ad libitum use period. In addition, pharmacodynamic effects (PD), including subjective effects and related behavioral assessments, as well as human puffing topography (HPT) will be evaluated, to provide further insights on P4M3 Gen 2.0 product acceptance and product use. Safety will be assessed throughout the study. The aim is to evaluate if P4M3 Gen 2.0 can provide an acceptable alternative to smoking cigarettes in terms of both, nicotine delivery and sensorial satisfaction for current adult smokers who would otherwise continue smoking cigarettes.
Interventions
OTHERCA35
Nicotine concentration: 3.5 % e-liquid flavor: Tobacco
OTHERCM35
Nicotine concentration: 3.5 % e-liquid flavor: Menthol
OTHERCig
Subjects' preferred brand of commercially available, regular or mentholated cigarettes
Sponsors
Philip Morris Products S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
24 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject has signed the ICF and is able to understand the information provided in the ICF. * Subject has smoked continuously for at least the last 3 years prior to the Screening visit. * Subject has smoked ≥ 10 commercially available cigarettes per day for 4 weeks prior to Screening Visit and Admission. * Subject does not plan to quit smoking cigarettes or using other nicotine or tobacco containing products in the next 3 months. * Smoking, healthy subject as judged by the Investigator or designee based on available assessments from the Screening period.
Exclusion criteria
* As per the Investigator's judgment, the subject cannot participate in the study for any reason other than medical. * Subject has donated or received whole blood or blood products within 30 days prior to Screening Visit. * BMI \< 18.5 kg/m2 or \> 35.0 kg/m2. * Subject has received medication within 14 days or within 5 half-lives of the drug prior to Admission (whichever is longer), which has an impact on CYP2A6 activity. * Subject has a positive serology test for HIV 1/2, Hepatitis B or Hepatitis C. * Subject has a history of alcohol abuse that could interfere with the subject's participation in study. * Subject has a positive urine drug test. * Subject has a positive alcohol breath test. * Subject has participated in another clinical study within 30 days prior to the Screening Visit. * Subject is pregnant (does not have negative pregnancy tests at Screening Visit and at Admission) or is breastfeeding. * For women of childbearing potential only: subject does not agree to use an acceptable method of effective contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Background-corrected Maximum Plasma Concentration [Cmax] | T0 = start of product use. From day 1 to day 3, blood was drawn 5 minutes prior to T0 (day 1 only), and then 1, 2, 4, 6, 8, 10, 12, 15, 30 minutes, 1, 2, 4, 10 and 24 hours after T0. (Note that sample taken 24 hours after T0 on day 1 and day 2 only.) | To measure Cmax from 6 minutes ad libitum use for two e-liquid variants used with the P4M3 Gen 2.0 e-cigarette and for subjects smoking cigarettes. |
| Background-corrected Time to the Maximum Concentration [Tmax] | T0 = start of product use. From day 1 to day 3, blood was drawn 5 minutes prior to T0 (day 1 only), and then 1, 2, 4, 6, 8, 10, 12, 15, 30 minutes, 1, 2, 4, 10 and 24 hours after T0. (Note that sample taken 24 hours after T0 on day 1 and day 2 only.) | To measure Tmax from 6 minutes ad libitum use for two e-liquid variants used with the P4M3 Gen 2.0 e-cigarette and for subjects smoking cigarettes. |
| Area Under the Background-corrected Concentration-time Curve From Start of Product Use to Time of Last Quantifiable Concentration and Extrapolated to Infinity. | T0 = start of product use. From day 1 to day 3, blood was drawn 5 minutes prior to T0 (day 1 only), and then 1, 2, 4, 6, 8, 10, 12, 15, 30 minutes, 1, 2, 4, 10 and 24 hours after T0. (Note that sample taken 24 hours after T0 on day 1 and day 2 only.) | To measure the area under the background-corrected concentration-time curve (AUC) from start of product use from 6 minutes ad libitum use for two e-liquid variants used with the P4M3 Gen 2.0 e-cigarette and for subjects smoking cigarettes. |
| Maximum Ratio of Background-corrected Concentration Over Time | T0 = start of product use. From day 1 to day 3, blood was drawn 5 minutes prior to T0 (day 1 only), and then 1, 2, 4, 6, 8, 10, 12, 15, 30 minutes, 1, 2, 4, 10 and 24 hours after T0. (Note that sample taken 24 hours after T0 on day 1 and day 2 only.) | To measure the maximum ratio of background-corrected concentration over time, from T0 (excluded) to Tmax (included) |
Countries
United States
Participant flow
Recruitment details
36 subjects were enrolled in the study, which was conducted at a clinical trial facility managed by a contract research organization.
Pre-assignment details
The 36 enrolled subjects were each randomized to one of six possible use sequences of product use.
Participants by arm
| Arm | Count |
|---|---|
| Safety Population Safety Population = All subjects who were exposed to the investigational product | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | Safety Population |
|---|---|
| Age, Continuous | 43.6 years STANDARD_DEVIATION 11.1 |
| BMI | 29.783 kg/m² STANDARD_DEVIATION 3.534 |
| Race/Ethnicity, Customized Black or African American | 25 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 0 Participants |
| Race/Ethnicity, Customized White | 10 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 32 | 0 / 33 | 0 / 34 |
| other Total, other adverse events | 0 / 35 | 0 / 32 | 0 / 33 | 0 / 34 |
| serious Total, serious adverse events | 0 / 35 | 0 / 32 | 0 / 33 | 0 / 34 |
Outcome results
Primary
Area Under the Background-corrected Concentration-time Curve From Start of Product Use to Time of Last Quantifiable Concentration and Extrapolated to Infinity.
To measure the area under the background-corrected concentration-time curve (AUC) from start of product use from 6 minutes ad libitum use for two e-liquid variants used with the P4M3 Gen 2.0 e-cigarette and for subjects smoking cigarettes.
Time frame: T0 = start of product use. From day 1 to day 3, blood was drawn 5 minutes prior to T0 (day 1 only), and then 1, 2, 4, 6, 8, 10, 12, 15, 30 minutes, 1, 2, 4, 10 and 24 hours after T0. (Note that sample taken 24 hours after T0 on day 1 and day 2 only.)
Population: The analysis population was a subset of the Safety Population and consisted of all randomized subjects, without major protocol deviations, for whom at least one nicotine PK parameter could be derived.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| CA35 | Area Under the Background-corrected Concentration-time Curve From Start of Product Use to Time of Last Quantifiable Concentration and Extrapolated to Infinity. | 891.1 min*ng/mL |
| CM35 | Area Under the Background-corrected Concentration-time Curve From Start of Product Use to Time of Last Quantifiable Concentration and Extrapolated to Infinity. | 655.6 min*ng/mL |
| Cigarettes | Area Under the Background-corrected Concentration-time Curve From Start of Product Use to Time of Last Quantifiable Concentration and Extrapolated to Infinity. | 2484 min*ng/mL |
Comparison: The objective of this study was to determine the AUC0-infinity ratio of P4M3 variants:Cigarettes along with the corresponding 95% confidence intervals95% CI: [16, 50.04]Mixed Models Analysis
Comparison: The objective of this study was to determine the AUC0-infinity ratio of P4M3 variants:Cigarettes along with the corresponding 95% confidence intervals95% CI: [12.74, 53.69]Mixed Models Analysis
Primary
Background-corrected Maximum Plasma Concentration [Cmax]
To measure Cmax from 6 minutes ad libitum use for two e-liquid variants used with the P4M3 Gen 2.0 e-cigarette and for subjects smoking cigarettes.
Time frame: T0 = start of product use. From day 1 to day 3, blood was drawn 5 minutes prior to T0 (day 1 only), and then 1, 2, 4, 6, 8, 10, 12, 15, 30 minutes, 1, 2, 4, 10 and 24 hours after T0. (Note that sample taken 24 hours after T0 on day 1 and day 2 only.)
Population: The analysis population was a subset of the Safety Population and consisted of all randomized subjects, without major protocol deviations, for whom at least one nicotine PK parameter could be derived.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| CA35 | Background-corrected Maximum Plasma Concentration [Cmax] | 2.934 (ng/mL) |
| CM35 | Background-corrected Maximum Plasma Concentration [Cmax] | 3.365 (ng/mL) |
| Cigarettes | Background-corrected Maximum Plasma Concentration [Cmax] | 17.49 (ng/mL) |
Comparison: The objective of this study was to determine the Cmax ratio of P4M3 variants:Cigarettes along with the corresponding 95% confidence intervals95% CI: [10.69, 27.19]Mixed Models Analysis
Comparison: The objective of this study was to determine the Cmax ratio of P4M3 variants:Cigarettes along with the corresponding 95% confidence intervals95% CI: [11.89, 31.87]Mixed Models Analysis
Primary
Background-corrected Time to the Maximum Concentration [Tmax]
To measure Tmax from 6 minutes ad libitum use for two e-liquid variants used with the P4M3 Gen 2.0 e-cigarette and for subjects smoking cigarettes.
Time frame: T0 = start of product use. From day 1 to day 3, blood was drawn 5 minutes prior to T0 (day 1 only), and then 1, 2, 4, 6, 8, 10, 12, 15, 30 minutes, 1, 2, 4, 10 and 24 hours after T0. (Note that sample taken 24 hours after T0 on day 1 and day 2 only.)
Population: The analysis population was a subset of the Safety Population and consisted of all randomized subjects, without major protocol deviations, for whom at least one nicotine PK parameter could be derived.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CA35 | Background-corrected Time to the Maximum Concentration [Tmax] | 109.3 minutes |
| CM35 | Background-corrected Time to the Maximum Concentration [Tmax] | 37.79 minutes |
| Cigarettes | Background-corrected Time to the Maximum Concentration [Tmax] | 7.826 minutes |
Comparison: The objective of this study was to determine the Tmax difference of P4M3 variants:Cigarettes along with the corresponding 95% confidence intervals95% CI: [0, 11]Wilcoxon signed rank test
Comparison: The objective of this study was to determine the Tmax difference of P4M3 variants:Cigarettes along with the corresponding 95% confidence intervals95% CI: [0, 4]Wilcoxon signed rank test
Primary
Maximum Ratio of Background-corrected Concentration Over Time
To measure the maximum ratio of background-corrected concentration over time, from T0 (excluded) to Tmax (included)
Time frame: T0 = start of product use. From day 1 to day 3, blood was drawn 5 minutes prior to T0 (day 1 only), and then 1, 2, 4, 6, 8, 10, 12, 15, 30 minutes, 1, 2, 4, 10 and 24 hours after T0. (Note that sample taken 24 hours after T0 on day 1 and day 2 only.)
Population: The analysis population was a subset of the Safety Population and consisted of all randomized subjects, without major protocol deviations, for whom at least one nicotine PK parameter could be derived.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| CA35 | Maximum Ratio of Background-corrected Concentration Over Time | 0.3547 (ng/mL)/min |
| CM35 | Maximum Ratio of Background-corrected Concentration Over Time | 0.5150 (ng/mL)/min |
| Cigarettes | Maximum Ratio of Background-corrected Concentration Over Time | 3.239 (ng/mL)/min |
Comparison: The objective of this study was to determine the maximum ratio of background-corrected concentration over time of P4M3 variants:Cigarettes along with the corresponding 95% confidence intervals95% CI: [5.57, 21.1]Mixed Models Analysis
Comparison: The objective of this study was to determine the maximum ratio of background-corrected concentration over time of P4M3 variants:Cigarettes along with the corresponding 95% confidence intervals95% CI: [9.93, 28.53]Mixed Models Analysis