Smoking
Conditions
Keywords
smoking, nicotine absorption, potential modified risk tobacco product, cigarette, Carbon Heated Tobacco Product
Brief summary
The primary objective of this clinical study is to evaluate the pharmacokinetic (PK) profile of nicotine (rate and amount of nicotine absorbed) after single use of the Carbon Heated Tobacco Product 1.1 Menthol (CHTP 1.1 M), a potential Modified Risk Tobacco Product, compared to menthol cigarettes (mCC) in healthy smokers.
Interventions
OTHERmCC
Single use of subject's own menthol conventional cigarette (mCC)
OTHERCHTP 1.1 M
Single use of the Carbon Heated Tobacco Product 1.1 Menthol (CHTP 1.1 M)
Sponsors
Philip Morris Products S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
23 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subject is Japanese. * Subject is at a minimum 23 years of age. * Smoking, healthy subject as judged by the Investigator. * Subject has smoked for at least the last 3 years * Subject smoked at least 10 commercially available mCCs per day over the last 4 weeks.
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 received medication within 14 days or within 5 half-lives of a drug (whichever is longer) which has an impact on CYP2A6 activity. * Female subject is pregnant or breast feeding. * Female subject does not agree to use an acceptable method of effective contraception.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Concentration (Cmax) of Nicotine Following Single Use of CHTP 1.1 M and mCC | Day 3: blood taken 15 minutes prior to T0, 2, 4, 6, 8, 10, 15, 30, 45 minutes, 1, 2, 4, 6, 9, 12, and 24 hours after T0. | T0 = start of single product use. Derived from multiple blood sampling on Day 1 and Day 3 (1 blood sampling pre-product use and multiple blood sampling over 24 hours post-product use). Geometric Least Squares (LS) means are provided. |
| Area Under the Plasma Concentration Versus Time Curve From Time Zero (Pre-product Use) to Last Time Point [AUC(0-last)] Following Single Use of CHTP 1.1 M and mCC | Day 3: blood taken 15 minutes prior to T0, 2, 4, 6, 8, 10, 15, 30, 45 minutes, 1, 2, 4, 6, 9, 12, and 24 hours after T0. | T0 = start of single product use. Derived from multiple blood sampling on Day 1 and Day 3 (1 blood sampling pre-product use and multiple blood sampling over 24 hours post-product use). Geometric Least Squares means are provided. |
Countries
Japan
Participant flow
Recruitment details
Study initiated (first subject screened): 08 May 2015 On Day -3 (admission), after all inclusion/exclusion criteria were checked, all eligible subjects were enrolled and tried CHTP 1.1 M. From enrollment, they were asked to remain abstinent from smoking for at least 24 hours before being randomized on Day 1 into 1 of the 2 sequences.
Pre-assignment details
Number of subjects enrolled = 56, but only 48 were randomized as described below: * Sequence CHTP 1.1 M then mCC: 24 subjects * Sequence mCC then CHTP 1.1 M: 24 subjects Number of subjects enrolled but NOT randomized = 8
Participants by arm
| Arm | Count |
|---|---|
| CHTP 1.1 M Then mCC Each subject will follow the below study design:
* Day -1 = Wash-out (1 day)
* Day 1 = 1st intervention (single product use of CHTP 1.1 M)
* Day 2 = Wash-out
* Day 3 = 2nd intervention (single product use of mCC). | 23 |
| mCC Then CHTP 1.1 M Each subject will follow the below study design:
* Day -1 = Wash-out (1 day)
* Day 1 = 1st intervention (single product use of mCC)
* Day 2 = Wash-out
* Day 3 = 2nd intervention (single product use of CHTP 1.1 M). | 24 |
| Total | 47 |
Baseline characteristics
| Characteristic | mCC Then CHTP 1.1 M | Total | CHTP 1.1 M Then mCC |
|---|---|---|---|
| Age, Continuous | 40.7 years STANDARD_DEVIATION 11.48 | 42.6 years STANDARD_DEVIATION 10.86 | 44.7 years STANDARD_DEVIATION 10.03 |
| International Organization for Standardization (ISO) nicotine Yield ≤ 0.6 mg | 11 Participants | 22 Participants | 11 Participants |
| International Organization for Standardization (ISO) nicotine Yield > 0.6 to ≤ 1 mg | 13 Participants | 25 Participants | 12 Participants |
| Sex: Female, Male Female | 14 Participants | 25 Participants | 11 Participants |
| Sex: Female, Male Male | 10 Participants | 22 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 24 | 0 / 24 | 0 / 8 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 | 0 / 8 |
Outcome results
Primary
Area Under the Plasma Concentration Versus Time Curve From Time Zero (Pre-product Use) to Last Time Point [AUC(0-last)] Following Single Use of CHTP 1.1 M and mCC
T0 = start of single product use. Derived from multiple blood sampling on Day 1 and Day 3 (1 blood sampling pre-product use and multiple blood sampling over 24 hours post-product use). Geometric Least Squares means are provided.
Time frame: Day 3: blood taken 15 minutes prior to T0, 2, 4, 6, 8, 10, 15, 30, 45 minutes, 1, 2, 4, 6, 9, 12, and 24 hours after T0.
Population: The PK population consisted of 47 subjects.~1 subject was excluded from the PK population (sequence CHTP 1.1 M then mCC) due to all plasma nicotine concentration measurements being below the quantification limit for both CHTP 1.1 M and mCC.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| CHTP 1.1 M | Area Under the Plasma Concentration Versus Time Curve From Time Zero (Pre-product Use) to Last Time Point [AUC(0-last)] Following Single Use of CHTP 1.1 M and mCC | 8.5311 h*ng/mL |
| Menthol Cigarette (mCC) | Area Under the Plasma Concentration Versus Time Curve From Time Zero (Pre-product Use) to Last Time Point [AUC(0-last)] Following Single Use of CHTP 1.1 M and mCC | 14.2172 h*ng/mL |
Comparison: The objective of this study was to determine the point estimate and precision of the CHTP 1.1 M:mCC ratio for AUC(0-last). Therefore, there was no statistical hypothesis to be tested for this objective.95% CI: [44.9517, 80.0997]ANOVA
Primary
Maximum Concentration (Cmax) of Nicotine Following Single Use of CHTP 1.1 M and mCC
T0 = start of single product use. Derived from multiple blood sampling on Day 1 and Day 3 (1 blood sampling pre-product use and multiple blood sampling over 24 hours post-product use). Geometric Least Squares (LS) means are provided.
Time frame: Day 3: blood taken 15 minutes prior to T0, 2, 4, 6, 8, 10, 15, 30, 45 minutes, 1, 2, 4, 6, 9, 12, and 24 hours after T0.
Population: The PK population consisted of 47 subjects.~1 subject was excluded from the PK population (sequence CHTP 1.1 M then mCC) due to all plasma nicotine concentration measurements being below the quantification limit for both CHTP 1.1 M and mCC.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| CHTP 1.1 M | Maximum Concentration (Cmax) of Nicotine Following Single Use of CHTP 1.1 M and mCC | 6.2950 ng/mL |
| Menthol Cigarette (mCC) | Maximum Concentration (Cmax) of Nicotine Following Single Use of CHTP 1.1 M and mCC | 9.8463 ng/mL |
Comparison: The objective of this study was to determine the point estimate and precision of the CHTP 1.1 M:mCC ratio for Cmax. Therefore, there was no statistical hypothesis to be tested for this objective.95% CI: [49.6045, 82.3991]ANOVA