Smoking
Conditions
Keywords
Smoking, Cigarettes, Reduced exposure, Confinement, Ambulatory, Carbon Heated Tobacco Product
Brief summary
The overall goal of the study is to demonstrate reduction in the levels of biomarkers of exposure (BoExp) to selected harmful and potentially harmful constituents (HPHCs) identified in cigarettes and to obtain safety information in healthy adult smokers switching to the Carbon Heated Tobacco Product 1.2 (CHTP 1.2) as compared to subjects continuing smoking cigarettes (CC) in a confinement setting for 5 days (exclusive use) followed by an ambulatory setting of 85 days.
Interventions
OTHERCHTP 1.2
Ad libitum use of the CHTP 1.2 for 5 days in confinement followed by 85 days in an ambulatory setting.
OTHERCC
Ad libitum use of subject's own preferred non-menthol brand of CC for 5 days in confinement followed by 85 days in an ambulatory setting.
Sponsors
Philip Morris Products S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
28 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Subject is aged ≥ 28 years. * Subject is Caucasian. * Subject is healthy, as judged by the Investigator. * Subject has smoked at least 10 commercially available non-menthol CCs per day (no brand restrictions) at least for the last 6 weeks prior to the screening visit and admission. * Subject has smoked at least for the last 10 years. * Subject does not plan to quit smoking in the next 6 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 |
|---|---|---|
| Concentrations of Monohydroxybutenylmercapturic Acid (MHBMA) | 5 days | Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric least squares (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors. |
| Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA) | 5 days | Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric least squares (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors. |
| Concentration of S-phenylmercapturic Acid (S-PMA) | 5 days | Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric least squares (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors. |
| 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 (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors. |
| Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL) | 90 days | Concentrations measured at Day 90 in urine, adjusted for creatinine. Geometric least squares (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 90 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors. |
Countries
Poland
Participant flow
Pre-assignment details
Following enrollment of 121 subjects, each subject received a product test of CHTP 1.2 prior to randomization. One subject was not randomized due to the physician's decision. This subject is included in the Exposed Not Randomized reporting group of the Baseline Characteristics. Consequently, 120 subjects were randomized.
Participants by arm
| Arm | Count |
|---|---|
| CHTP 1.2 Ad libitum use of the CHTP 1.2
CHTP 1.2: Ad libitum use of the CHTP 1.2 for 5 days in confinement followed by 85 days in an ambulatory setting. | 80 |
| Cigarettes (CC) Ad libitum use of subject's own preferred non-menthol brand of CC
CC: Ad libitum use of subject's own preferred non-menthol brand of CC for 5 days in confinement followed by 85 days in an ambulatory setting. | 40 |
| Exposed Not Randomized Exposed not randomized refers to all subjects exposed to CHTP 1.2 but not randomized. | 1 |
| Total | 121 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Ambulatory Period | Withdrawal by Subject | 1 | 0 |
| Confinement Period | Adverse Event | 1 | 0 |
| Confinement Period | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | CHTP 1.2 | Total | Exposed Not Randomized | Cigarettes (CC) |
|---|---|---|---|---|
| Age, Continuous | 38.9 Years STANDARD_DEVIATION 8.9 | 38.8 Years STANDARD_DEVIATION 8.6 | 28 Years | 39.0 Years STANDARD_DEVIATION 8 |
| BMI | 25.74 kg/m2 STANDARD_DEVIATION 3.51 | 25.69 kg/m2 STANDARD_DEVIATION 3.33 | 21.7 kg/m2 | 25.70 kg/m2 STANDARD_DEVIATION 2.96 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 80 Participants | 120 Participants | 0 Participants | 40 Participants |
| Sex: Female, Male Female | 36 Participants | 57 Participants | 1 Participants | 20 Participants |
| Sex: Female, Male Male | 44 Participants | 64 Participants | 0 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 121 | 0 / 80 | 0 / 40 | 0 / 77 | 0 / 39 | 0 / 80 | 0 / 40 | 0 / 80 | 0 / 40 |
| other Total, other adverse events | 62 / 121 | 37 / 80 | 12 / 40 | 50 / 77 | 26 / 39 | 1 / 80 | 1 / 40 | 64 / 80 | 31 / 40 |
| serious Total, serious adverse events | 0 / 121 | 1 / 80 | 0 / 40 | 1 / 77 | 1 / 39 | 0 / 80 | 0 / 40 | 2 / 80 | 1 / 40 |
Outcome results
Primary
Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA)
Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric least squares (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors.
Time frame: 5 days
Population: Per Protocol (PP) population
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| CHTP 1.2 | Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA) | 616.8 ng/mg creat |
| Cigarettes (CC) | Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA) | 1031 ng/mg creat |
Comparison: Analysis will be conducted on the natural log scale. The Day 5 levels of 3-HPMA will be analyzed by means of a generalized linear model using randomized arm as covariate adjusting for sex, average cigarette consumption over the previous 6 weeks prior to Admission (value at Admission for stratification), and log-transformed baseline value of 3-HPMA.p-value: <0.00195% CI: [30.25, 48.73]Generalized linear model
Primary
Concentration of S-phenylmercapturic Acid (S-PMA)
Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric least squares (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors.
Time frame: 5 days
Population: Per Protocol (PP) population
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| CHTP 1.2 | Concentration of S-phenylmercapturic Acid (S-PMA) | 386.6 pg/mg creat |
| Cigarettes (CC) | Concentration of S-phenylmercapturic Acid (S-PMA) | 2401 pg/mg creat |
Comparison: Analysis will be conducted on the natural log scale. The Day 5 levels of S-PMA will be analyzed by means of a generalized linear model using randomized arm as covariate adjusting for sex, average cigarette consumption over the previous 6 weeks prior to Admission (value at Admission for stratification), and log-transformed baseline value of S-PMA.p-value: <0.00195% CI: [81.61, 85.9]Generalized linear model
Primary
Concentrations of Monohydroxybutenylmercapturic Acid (MHBMA)
Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric least squares (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors.
Time frame: 5 days
Population: Per Protocol (PP) population
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| CHTP 1.2 | Concentrations of Monohydroxybutenylmercapturic Acid (MHBMA) | 285.5 pg/mg creat |
| Cigarettes (CC) | Concentrations of Monohydroxybutenylmercapturic Acid (MHBMA) | 1904 pg/mg creat |
Comparison: Analysis will be conducted on the natural log scale. The Day 5 levels of MHBMA will be analyzed by means of a generalized linear model using randomized arm as covariate adjusting for sex, average cigarette consumption over the previous 6 weeks prior to Admission (value at Admission for stratification), and log-transformed baseline value of MHBMA.p-value: <0.00195% CI: [82.06, 87.47]Generalized linear model
Primary
Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL)
Concentrations measured at Day 90 in urine, adjusted for creatinine. Geometric least squares (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 90 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors.
Time frame: 90 days
Population: Per Protocol (PP) population
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| CHTP 1.2 | Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL) | 37.26 pg/mg creat |
| Cigarettes (CC) | Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL) | 180.6 pg/mg creat |
Comparison: Analysis will be conducted on the natural log scale. The Day 5 levels of Total NNAL will be analyzed by means of a generalized linear model using randomized arm as covariate adjusting for sex, average cigarette consumption over the previous 6 weeks prior to Admission (value at Admission for stratification), and log-transformed baseline value of Total NNAL.p-value: <0.00195% CI: [72.73, 84.39]Generalized linear model
Primary
Levels of Carboxyhemoglobin (COHb)
% COHb blood measurements performed in the evening of Day 5, expressed as % of saturation of hemoglobin. Geometric least squares (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors.
Time frame: 5 days
Population: Per Protocol (PP) population
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| CHTP 1.2 | Levels of Carboxyhemoglobin (COHb) | 2.01 % of saturation of hemoglobin |
| Cigarettes (CC) | Levels of Carboxyhemoglobin (COHb) | 4.53 % of saturation of hemoglobin |
Comparison: Analysis will be conducted on the natural log scale. The Day 5 levels of COHb will be analyzed by means of a generalized linear model using randomized arm as covariate adjusting for sex, average cigarette consumption over the previous 6 weeks prior to Admission (value at Admission for stratification), and log-transformed baseline value of COHb.p-value: <0.00195% CI: [49.03, 61.56]Generalized linear model