Smoking
Conditions
Keywords
Smoking, Modified risk tobacco product, Conventional cigarette, Reduced exposure, Confinement, Carbon Heated Tobacco Product
Brief summary
The overall goal of the study is to demonstrate the reduction of biomarkers of exposure (BoExp) to selected harmful and potentially harmful constituents (HPHCs) in adult smokers switching for 5 days from conventional cigarette (CC) to Carbon Heated Tobacco Product 1.0 (CHTP 1.0) as compared to smokers continuing to use CC.
Interventions
OTHERCHTP 1.0
CHTP 1.0 ad libitum for 5 days in confinement
Subject's own preferred brand of CC ad libitum for 5 days in confinement
Sponsors
Philip Morris Products S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subject is aged ≥ 21 years. * Subject is Caucasian. * Subject is healthy, as judged by the Investigator. * Subject smokes at least 10 commercially available non-menthol CCs per day (no brand restrictions) for at least the last 6 weeks prior to admission, based on self-reporting. * Subject has smoked at least for the last 3 years. * Subject does not plan to quit smoking in the next 3 months.
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 the medication (whichever is longer), which has an impact on cytochrome P450 1A2 (CYP1A2) or cytochrome P450 2A6 (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 |
|---|---|---|
| Concentration of Monohydroxybutenyl Mercapturic Acid (MHBMA) | 5 days | Concentrations measured on Day 5 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics. |
| Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA) | 5 days | Concentrations measured on Day 5 in urine, adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics. |
| Concentration of S-phenylmercapturic Acid (S-PMA) | 5 days | Concentrations measured on Day 5 in urine, adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics. |
| Levels of Carboxyhemoglobin (COHb) | 5 days | % COHb blood measurements performed in the evening of Day 5, expressed as % of saturation of hemoglobin. Geometric Least Squares means are provided as descriptive statistics. |
Countries
Poland
Participant flow
Recruitment details
Study initiated (first subject screened): 04 July 2015 At admission (Day -3), all the subjects performed a product trial of the CHTP 1.0. During the baseline period, they continued smoking their single preferred brand of CC. Then, on Day -1, subjects were randomized to one of the two study arms (CHTP 1.0 or CC) in a 1:1 ratio.
Pre-assignment details
Enrolled and randomized population = 80 subjects * 41 subjects in CHTP 1.0 arm * 39 subjects in CC arm Number of subjects enrolled but NOT randomized (who tried the CHTP 1.0 at Day -3) = 5
Participants by arm
| Arm | Count |
|---|---|
| CHTP 1.0 Ad libitum use of the Carbon Heated Tobacco Product 1.0 (CHTP 1.0) for 5 days in confinement | 41 |
| Conventional Cigarette (CC) Ad libitum use of subject's own preferred brand of CC for 5 days in confinement | 39 |
| Total | 80 |
Baseline characteristics
| Characteristic | Conventional Cigarette (CC) | Total | CHTP 1.0 |
|---|---|---|---|
| Age, Continuous | 32.7 years STANDARD_DEVIATION 10.97 | 33.5 years STANDARD_DEVIATION 10.66 | 34.1 years STANDARD_DEVIATION 10.45 |
| International Organization for Standardization (ISO) nicotine level ≤ 0.6 mg | 34 Participants | 66 Participants | 32 Participants |
| International Organization for Standardization (ISO) nicotine level > 0.6 to ≤ 1 mg | 5 Participants | 14 Participants | 9 Participants |
| Sex: Female, Male Female | 20 Participants | 41 Participants | 21 Participants |
| Sex: Female, Male Male | 19 Participants | 39 Participants | 20 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 | 27 / 41 | 14 / 39 | 5 / 5 |
| serious Total, serious adverse events | 0 / 41 | 0 / 39 | 1 / 5 |
Outcome results
Primary
Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA)
Concentrations measured on Day 5 in urine, adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics.
Time frame: 5 days
Population: The analysis was performed on the full analysis set (FAS) population.~The FAS consisted of all the randomized subjects who had at least 1 post randomization product use experience (CHTP 1.0 or CC) and had at least 1 non-safety assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| CHTP 1.0 | Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA) | 464.27 ng/mg creat |
| Conventional Cigarette (CC) | Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA) | 1272.96 ng/mg creat |
Comparison: The hypothesis to be tested is that the geometric mean level on Day 5 of the biomarker of exposure for CHTP 1.0 is lower relative to CC.~Analysis of the BoExp was conducted on the natural log scale in order to test the following hypothesis (one sided test with 2.5% type I error probability):~* Null hypothesis (H0): m1≥m2~* Alternative hypothesis (H1): m1\<m2 Where m1 and m2 are the geometric means of the BoExp levels on Day 5 for CHTP 1.0 and CC, respectivelyp-value: <0.00195% CI: [59.55, 67.12]ANCOVA
Primary
Concentration of Monohydroxybutenyl Mercapturic Acid (MHBMA)
Concentrations measured on Day 5 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics.
Time frame: 5 days
Population: The analysis was performed on the full analysis set (FAS) population.~The FAS consisted of all the randomized subjects who had at least 1 post randomization product use experience (CHTP 1.0 or CC) and had at least 1 non-safety assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| CHTP 1.0 | Concentration of Monohydroxybutenyl Mercapturic Acid (MHBMA) | 327.08 pg/mg creat |
| Conventional Cigarette (CC) | Concentration of Monohydroxybutenyl Mercapturic Acid (MHBMA) | 1903.61 pg/mg creat |
Comparison: The hypothesis to be tested is that the geometric mean level on Day 5 of the biomarker of exposure for CHTP 1.0 is lower relative to CC.~Analysis of the BoExp was conducted on the natural log scale in order to test the following hypothesis (one sided test with 2.5% type I error probability):~* Null hypothesis (H0): m1≥m2~* Alternative hypothesis (H1): m1\<m2 Where m1 and m2 are the geometric means of the BoExp levels on Day 5 for CHTP 1.0 and CC, respectively.p-value: <0.00195% CI: [78.79, 86.09]ANCOVA
Primary
Concentration of S-phenylmercapturic Acid (S-PMA)
Concentrations measured on Day 5 in urine, adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics.
Time frame: 5 days
Population: The analysis was performed on the full analysis set (FAS) population.~The FAS consisted of all the randomized subjects who had at least 1 post randomization product use experience (CHTP 1.0 or CC) and had at least 1 non-safety assessment.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| CHTP 1.0 | Concentration of S-phenylmercapturic Acid (S-PMA) | 352.39 pg/mg creat |
| Conventional Cigarette (CC) | Concentration of S-phenylmercapturic Acid (S-PMA) | 2971.98 pg/mg creat |
Comparison: The hypothesis to be tested is that the geometric mean level on Day 5 of the biomarker of exposure for CHTP 1.0 is lower relative to CC.~Analysis of the BoExp was conducted on the natural log scale in order to test the following hypothesis (one sided test with 2.5% type I error probability):~* Null hypothesis (H0): m1≥m2~* Alternative hypothesis (H1): m1\<m2 Where m1 and m2 are the geometric means of the BoExp levels on Day 5 for CHTP 1.0 and CC, respectively.p-value: <0.00195% CI: [86.46, 89.62]ANCOVA
Primary
Levels of Carboxyhemoglobin (COHb)
% COHb blood measurements performed in the evening of Day 5, expressed as % of saturation of hemoglobin. Geometric Least Squares means are provided as descriptive statistics.
Time frame: 5 days
Population: The analysis was performed on the full analysis set (FAS) population: all randomized subjects who had at least 1 post randomization product use experience (CHTP 1.0 or CC) and had at least 1 non-safety assessment.~However, due to sample issues such as clotting, COHb assessment results could not be generated for some of the subjects.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| CHTP 1.0 | Levels of Carboxyhemoglobin (COHb) | 2.660 percentage of saturation of hemoglobin |
| Conventional Cigarette (CC) | Levels of Carboxyhemoglobin (COHb) | 6.460 percentage of saturation of hemoglobin |
Comparison: The hypothesis to be tested is that the geometric mean level on Day 5 of the biomarker of exposure for CHTP 1.0 is lower relative to CC.~Analysis of the BoExp was conducted on the natural log scale in order to test the following hypothesis (one sided test with 2.5% type I error probability):~* Null hypothesis (H0): m1≥m2~* Alternative hypothesis (H1): m1\<m2 Where m1 and m2 are the geometric means of the BoExp levels on Day 5 for CHTP 1.0 and CC respectively.p-value: <0.00195% CI: [49.3, 66.56]ANCOVA