Trial Outcomes & Findings for Reduced Exposure Study Using the CHTP 1.2 With 5 Days in a Confinement Setting Followed by 85 Days in an Ambulatory Setting. (NCT NCT02641587)

NCT ID: NCT02641587

Last Updated: 2023-02-21

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 121 participants
• Primary outcome timeframe: 5 days
• Results posted on: 2023-02-21

Participant Flow

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.

Participant milestones

Measure	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.	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.
Confinement Period STARTED	80	40
Confinement Period COMPLETED	77	39
Confinement Period NOT COMPLETED	3	1
Ambulatory Period STARTED	77	39
Ambulatory Period COMPLETED	76	39
Ambulatory Period NOT COMPLETED	1	0

Reasons for withdrawal

Measure	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.	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.
Confinement Period Adverse Event	1	0
Confinement Period Withdrawal by Subject	2	1
Ambulatory Period Withdrawal by Subject	1	0

Baseline Characteristics

Reduced Exposure Study Using the CHTP 1.2 With 5 Days in a Confinement Setting Followed by 85 Days in an Ambulatory Setting.

Baseline characteristics by cohort

Measure	CHTP 1.2 n=80 Participants 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.	Cigarettes (CC) n=40 Participants 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.	Exposed Not Randomized n=1 Participants "Exposed not randomized" refers to all subjects exposed to CHTP 1.2 but not randomized.	Total n=121 Participants Total of all reporting groups
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	38.9 Years STANDARD_DEVIATION 8.9 • n=5 Participants	39.0 Years STANDARD_DEVIATION 8.0 • n=7 Participants	28 Years n=5 Participants	38.8 Years STANDARD_DEVIATION 8.6 • n=4 Participants
Race (NIH/OMB) White	80 Participants n=5 Participants	40 Participants n=7 Participants	0 Participants n=5 Participants	120 Participants n=4 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	20 Participants n=7 Participants	1 Participants n=5 Participants	57 Participants n=4 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	20 Participants n=7 Participants	0 Participants n=5 Participants	64 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
BMI	25.74 kg/m2 STANDARD_DEVIATION 3.51 • n=5 Participants	25.70 kg/m2 STANDARD_DEVIATION 2.96 • n=7 Participants	21.7 kg/m2 n=5 Participants	25.69 kg/m2 STANDARD_DEVIATION 3.33 • n=4 Participants

PRIMARY outcome

Timeframe: 5 days

Population: Per Protocol (PP) population

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.

Outcome measures

Measure	CHTP 1.2 n=74 Participants 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.	Cigarettes (CC) n=34 Participants 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.
Concentrations of Monohydroxybutenylmercapturic Acid (MHBMA)	285.5 pg/mg creat Interval 258.0 to 315.8	1904 pg/mg creat Interval 1641.0 to 2209.0

PRIMARY outcome

Timeframe: 5 days

Population: Per Protocol (PP) population

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.

Outcome measures

Measure	CHTP 1.2 n=74 Participants 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.	Cigarettes (CC) n=34 Participants 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.
Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA)	616.8 ng/mg creat Interval 565.6 to 672.8	1031 ng/mg creat Interval 907.9 to 1172.0

PRIMARY outcome

Timeframe: 5 days

Population: Per Protocol (PP) population

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.

Outcome measures

Measure	CHTP 1.2 n=74 Participants 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.	Cigarettes (CC) n=34 Participants 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.
Concentration of S-phenylmercapturic Acid (S-PMA)	386.6 pg/mg creat Interval 358.7 to 416.7	2401 pg/mg creat Interval 2151.0 to 2681.0

PRIMARY outcome

Timeframe: 5 days

Population: Per Protocol (PP) population

% 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.

Outcome measures

Measure	CHTP 1.2 n=58 Participants 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.	Cigarettes (CC) n=22 Participants 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.
Levels of Carboxyhemoglobin (COHb)	2.01 % of saturation of hemoglobin Interval 1.86 to 2.16	4.53 % of saturation of hemoglobin Interval 4.01 to 5.11

PRIMARY outcome

Timeframe: 90 days

Population: Per Protocol (PP) population

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.

Outcome measures

Measure	CHTP 1.2 n=57 Participants 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.	Cigarettes (CC) n=35 Participants 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.
Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL)	37.26 pg/mg creat Interval 31.39 to 44.24	180.6 pg/mg creat Interval 144.8 to 225.1

Adverse Events

Product Test

Serious events: 0 serious events

Other events: 62 other events

Deaths: 0 deaths

CHTP 1.2 Confinement

Serious events: 1 serious events

Other events: 37 other events

Deaths: 0 deaths

CC Confinement

Serious events: 0 serious events

Other events: 12 other events

Deaths: 0 deaths

CHTP 1.2 Ambulatory

Serious events: 1 serious events

Other events: 50 other events

Deaths: 0 deaths

CC Ambulatory

Serious events: 1 serious events

Other events: 26 other events

Deaths: 0 deaths

CHTP 1.2 Safety FU

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

CC Safety FU

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

CHTP 1.2 Post-Randomization

Serious events: 2 serious events

Other events: 64 other events

Deaths: 0 deaths

CC Post-Randomization

Serious events: 1 serious events

Other events: 31 other events

Deaths: 0 deaths

Serious adverse events

Measure	Product Test n=121 participants at risk After all inclusion/exclusion criteria were checked, all eligible subjects were enrolled and performed a product test using up to five CHTP 1.2	CHTP 1.2 Confinement n=80 participants at risk Ad libitum use of the CHTP 1.2 for 5 days in confinement.	CC Confinement n=40 participants at risk Ad libitum use of subject's own preferred non-menthol brand of CC for 5 days in confinement.	CHTP 1.2 Ambulatory n=77 participants at risk Ad libitum use of the CHTP 1.2 for 85 days in an ambulatory setting.	CC Ambulatory n=39 participants at risk Ad libitum use of subject's own preferred non-menthol brand of CC for 85 days in an ambulatory setting.	CHTP 1.2 Safety FU n=80 participants at risk CHTP 1.2 Safety Follow-Up period of 28 days	CC Safety FU n=40 participants at risk CC Safety Follow-Up period of 28 days	CHTP 1.2 Post-Randomization n=80 participants at risk CHTP 1.2 Post-Randomization period	CC Post-Randomization n=40 participants at risk CC Post-Randomization period
Infections and infestations Appendicitis	0.00% 0/121 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	1.3% 1/77 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/39 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	1.2% 1/80 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.
Infections and infestations Peritonsillar Abscess	0.00% 0/121 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	1.2% 1/80 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/77 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/39 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	1.2% 1/80 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.
Injury, poisoning and procedural complications Joint Dislocation	0.00% 0/121 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/77 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	2.6% 1/39 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	2.5% 1/40 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.

Other adverse events

Measure	Product Test n=121 participants at risk After all inclusion/exclusion criteria were checked, all eligible subjects were enrolled and performed a product test using up to five CHTP 1.2	CHTP 1.2 Confinement n=80 participants at risk Ad libitum use of the CHTP 1.2 for 5 days in confinement.	CC Confinement n=40 participants at risk Ad libitum use of subject's own preferred non-menthol brand of CC for 5 days in confinement.	CHTP 1.2 Ambulatory n=77 participants at risk Ad libitum use of the CHTP 1.2 for 85 days in an ambulatory setting.	CC Ambulatory n=39 participants at risk Ad libitum use of subject's own preferred non-menthol brand of CC for 85 days in an ambulatory setting.	CHTP 1.2 Safety FU n=80 participants at risk CHTP 1.2 Safety Follow-Up period of 28 days	CC Safety FU n=40 participants at risk CC Safety Follow-Up period of 28 days	CHTP 1.2 Post-Randomization n=80 participants at risk CHTP 1.2 Post-Randomization period	CC Post-Randomization n=40 participants at risk CC Post-Randomization period
Nervous system disorders Headache	34.7% 42/121 • Number of events 54 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	11.2% 9/80 • Number of events 10 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	10.0% 4/40 • Number of events 7 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	18.2% 14/77 • Number of events 15 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	20.5% 8/39 • Number of events 9 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	25.0% 20/80 • Number of events 25 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	27.5% 11/40 • Number of events 16 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.
Infections and infestations Nasopharyngitis	2.5% 3/121 • Number of events 3 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	7.5% 6/80 • Number of events 6 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	5.0% 2/40 • Number of events 2 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	11.7% 9/77 • Number of events 9 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	2.6% 1/39 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	17.5% 14/80 • Number of events 15 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	7.5% 3/40 • Number of events 3 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.
Metabolism and nutrition disorders Hyperglycaemia	3.3% 4/121 • Number of events 4 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	2.5% 2/80 • Number of events 2 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	18.2% 14/77 • Number of events 15 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	10.3% 4/39 • Number of events 4 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	18.8% 15/80 • Number of events 17 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	10.0% 4/40 • Number of events 4 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.
Metabolism and nutrition disorders Hypertriglyceridaemia	6.6% 8/121 • Number of events 8 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	3.9% 3/77 • Number of events 3 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	2.6% 1/39 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	3.8% 3/80 • Number of events 3 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	2.5% 1/40 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	0.83% 1/121 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	2.5% 2/80 • Number of events 2 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	5.0% 2/40 • Number of events 2 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	3.9% 3/77 • Number of events 3 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	5.1% 2/39 • Number of events 2 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	6.2% 5/80 • Number of events 5 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	10.0% 4/40 • Number of events 4 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/121 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	5.0% 4/80 • Number of events 4 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	2.6% 2/77 • Number of events 2 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	5.1% 2/39 • Number of events 2 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	2.5% 1/40 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	7.5% 6/80 • Number of events 6 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	7.5% 3/40 • Number of events 3 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.
Investigations Alanine Aminotransferase Increased	0.83% 1/121 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	3.8% 3/80 • Number of events 3 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	3.9% 3/77 • Number of events 3 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	2.6% 1/39 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	7.5% 6/80 • Number of events 6 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	2.5% 1/40 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.
Investigations Blood Triglycerides Increased	0.83% 1/121 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	1.3% 1/77 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	5.1% 2/39 • Number of events 2 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	1.2% 1/80 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	5.0% 2/40 • Number of events 2 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.
Gastrointestinal disorders	1.7% 2/121 • Number of events 2 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	11.2% 9/80 • Number of events 9 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	5.0% 2/40 • Number of events 2 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	7.8% 6/77 • Number of events 6 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	5.1% 2/39 • Number of events 2 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	2.5% 1/40 • Number of events 3 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	15.0% 12/80 • Number of events 15 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	12.5% 5/40 • Number of events 7 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.
General disorders Vessel Puncture Site Bruise	5.0% 6/121 • Number of events 6 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	6.2% 5/80 • Number of events 5 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	2.5% 1/40 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/77 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/39 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	6.2% 5/80 • Number of events 5 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	2.5% 1/40 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.
Skin and subcutaneous tissue disorders Rash	0.00% 0/121 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	6.2% 5/80 • Number of events 5 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	1.3% 1/77 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/39 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	7.5% 6/80 • Number of events 6 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.
Musculoskeletal and connective tissue disorders	0.83% 1/121 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	5.0% 4/80 • Number of events 4 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	1.3% 1/77 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/39 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	6.2% 5/80 • Number of events 5 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.
Injury, poisoning and procedural complications	0.00% 0/121 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/77 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	5.1% 2/39 • Number of events 2 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	1.2% 1/80 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	1.2% 1/80 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	5.0% 2/40 • Number of events 2 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.
General disorders General disorders	5.0% 6/121 • Number of events 6 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	7.5% 6/80 • Number of events 6 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	7.5% 3/40 • Number of events 3 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	1.3% 1/77 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	2.6% 1/39 • Number of events 1 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/80 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	0.00% 0/40 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	8.8% 7/80 • Number of events 7 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.	10.0% 4/40 • Number of events 4 • Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.

Additional Information

Christelle Haziza

Philip Morris Products S.A.

Phone: +41 58 242 11 11

Email: christelle.haziza@pmi.com

Results disclosure agreements

• Principal investigator is a sponsor employee We confirm we have the contractual provisions in place which specify that in no event will the study site be allowed to disclose to any third party (or publicly release) any information obtained through the study without the CRO's prior written consent which in turn cannot provide such consent without Sponsor's approval unless such publication is made to satisfy regulatory requirements. The Intellectual Property rights and research results from the present study belong to the Sponsor.
• Publication restrictions are in place

Restriction type: OTHER