Trial Outcomes & Findings for Reduced Exposure Study in Smokers Using the Tobacco Heating System 2.2 (THS 2.2) for 5 Days in a Confinement Setting (NCT NCT01970982)

Results Overview

Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares LS) means are provided as descriptive statistics.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

166 participants

Primary outcome timeframe

5 days

Results posted on

2020-03-12

Participant Flow

Study initiated (first subject screened): 23 July 2013 At admission (Day -2), all the subjects performed a product trial of the THS 2.2. During the baseline period, they continued smoking their single preferred brand of CC. Then, on Day 0, subjects were randomized to one of the 3 study arms (THS 2.2, CC or SA) in a 2:1:1 ratio.

Enrolled and randomized population = 160 subjects * 80 subjects in THS 2.2 * 40 subjects in CC * 40 subjects in SA Number of subjects enrolled but NOT randomized (who tried the THS 2.2 at Day -2) = 6

Participant milestones

Participant milestones
Measure	Tobacco Heating System (THS 2.2) Ad libitum use of THS 2.2 for 5 days in confinement	Conventional Cigarette (CC) Ad libitum use of Subject's own preferred brand of CC for 5 days in confinement	Smoking Abstinence (SA) Abstinence from smoking for 5 days in confinement
Overall Study STARTED	80	40	40
Overall Study COMPLETED	80	40	38
Overall Study NOT COMPLETED	0	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Tobacco Heating System (THS 2.2) Ad libitum use of THS 2.2 for 5 days in confinement	Conventional Cigarette (CC) Ad libitum use of Subject's own preferred brand of CC for 5 days in confinement	Smoking Abstinence (SA) Abstinence from smoking for 5 days in confinement
Overall Study Withdrawal by Subject	0	0	2

Baseline Characteristics

Reduced Exposure Study in Smokers Using the Tobacco Heating System 2.2 (THS 2.2) for 5 Days in a Confinement Setting

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tobacco Heating System (THS 2.2) n=80 Participants Ad libitum use of THS 2.2 for 5 days in confinement	Conventional Cigarette (CC) n=40 Participants Ad libitum use of Subject's own preferred brand of CC for 5 days in confinement	Smoking Abstinence (SA) n=40 Participants Abstinence from smoking for 5 days in confinement	Total n=160 Participants Total of all reporting groups
Age, Customized Between 23 and 65 years	37.6 years STANDARD_DEVIATION 11.7 • n=5 Participants	37.2 years STANDARD_DEVIATION 11.7 • n=7 Participants	35.9 years STANDARD_DEVIATION 10.6 • n=5 Participants	37.1 years STANDARD_DEVIATION 11.4 • n=4 Participants
Sex: Female, Male Female	40 Participants n=5 Participants	20 Participants n=7 Participants	20 Participants n=5 Participants	80 Participants n=4 Participants
Sex: Female, Male Male	40 Participants n=5 Participants	20 Participants n=7 Participants	20 Participants n=5 Participants	80 Participants n=4 Participants
Daily CC consumption at Screening 10 to 19 cig/day	44 participants n=5 Participants	22 participants n=7 Participants	21 participants n=5 Participants	87 participants n=4 Participants
Daily CC consumption at Screening > 19 cig/day	36 participants n=5 Participants	18 participants n=7 Participants	19 participants n=5 Participants	73 participants n=4 Participants

PRIMARY outcome

Timeframe: 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 (if randomized to THS 2.2 or CC) and had at least 1 valid biomarker of exposure (BoExp) measurement (THS 2.2, CC, SA arms).

Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares LS) means are provided as descriptive statistics.

Outcome measures

Outcome measures
Measure	Tobacco Heating System (THS 2.2) n=80 Participants Ad libitum use of THS 2.2 for 5 days in confinement	Conventional Cigarette (CC) n=40 Participants Ad libitum use of subject's own preferred brand of CC for 5 days in confinement	Smoking Abstinence (SA) n=38 Participants Abstinence from smoking for 5 days in confinement
Concentration of Monohydroxybutenyl Mercapturic Acid (MHBMA)	106.25 pg/mg creat Interval 93.22 to 121.11	460.15 pg/mg creat Interval 382.54 to 553.51	91.73 pg/mg creat Interval 75.91 to 110.86

PRIMARY outcome

Timeframe: 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 (if randomized to THS 2.2 or CC) and had at least 1 valid BoExp measurement (THS 2.2, CC, SA arms).

Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics.

Outcome measures

Outcome measures
Measure	Tobacco Heating System (THS 2.2) n=80 Participants Ad libitum use of THS 2.2 for 5 days in confinement	Conventional Cigarette (CC) n=40 Participants Ad libitum use of subject's own preferred brand of CC for 5 days in confinement	Smoking Abstinence (SA) n=38 Participants Abstinence from smoking for 5 days in confinement
Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA)	311.68 ng/mg creat Interval 286.43 to 339.16	589.65 ng/mg creat Interval 523.25 to 664.47	204.23 ng/mg creat Interval 180.7 to 230.82

PRIMARY outcome

Timeframe: 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 (if randomized to THS 2.2 or CC) and had at least 1 valid BoExp measurement (THS 2.2, CC, SA arms).

Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics.

Outcome measures

Outcome measures
Measure	Tobacco Heating System (THS 2.2) n=80 Participants Ad libitum use of THS 2.2 for 5 days in confinement	Conventional Cigarette (CC) n=40 Participants Ad libitum use of subject's own preferred brand of CC for 5 days in confinement	Smoking Abstinence (SA) n=38 Participants Abstinence from smoking for 5 days in confinement
Concentration of S-phenylmercapturic Acid (S-PMA)	142.05 pg/mg creat Interval 127.98 to 157.65	905.89 pg/mg creat Interval 781.81 to 1049.67	122.02 pg/mg creat Interval 104.92 to 141.9

PRIMARY outcome

Timeframe: 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 (if randomized to THS 2.2 or CC) and had at least 1 valid BoExp measurement (THS 2.2, CC, SA arms).

% 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.

Outcome measures

Outcome measures
Measure	Tobacco Heating System (THS 2.2) n=80 Participants Ad libitum use of THS 2.2 for 5 days in confinement	Conventional Cigarette (CC) n=40 Participants Ad libitum use of subject's own preferred brand of CC for 5 days in confinement	Smoking Abstinence (SA) n=38 Participants Abstinence from smoking for 5 days in confinement
Levels of Carboxyhemoglobin (COHb)	2.41 % of saturation of hemoglobin Interval 2.33 to 2.51	5.13 % of saturation of hemoglobin Interval 4.87 to 5.39	2.37 % of saturation of hemoglobin Interval 2.24 to 2.5

Adverse Events

Tobacco Heating System (THS 2.2)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Conventional Cigarette (CC)

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Smoking Abstinence (SA)

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Enrolled But Not Randomized

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Tobacco Heating System (THS 2.2) n=80 participants at risk Ad libitum use of THS 2.2 for 5 days in confinement	Conventional Cigarette (CC) n=40 participants at risk Ad libitum use of Subject's own preferred brand of CC for 5 days in confinement	Smoking Abstinence (SA) n=40 participants at risk Abstinence from smoking for 5 days in confinement	Enrolled But Not Randomized n=6 participants at risk Subjects who tried the THS 2.2 at Admission (Day -2) but were not randomized in 1 of the 3 arms as they were back-up subjects
Investigations Blood triglycerides increased	2.5% 2/80 • Number of events 2 • From the informed consent form (ICF) signature until the end of the safety follow-up period (7 days after discharge of the subject). The safety was assessed in the safety population, consisting of 166 subjects: 160 randomized subjects (80 in THS 2.2, 40 in CC and 40 in SA) and 6 subjects exposed to THS 2.2 from the product trial on Day -2 but not randomized.	5.0% 2/40 • Number of events 2 • From the informed consent form (ICF) signature until the end of the safety follow-up period (7 days after discharge of the subject). The safety was assessed in the safety population, consisting of 166 subjects: 160 randomized subjects (80 in THS 2.2, 40 in CC and 40 in SA) and 6 subjects exposed to THS 2.2 from the product trial on Day -2 but not randomized.	0.00% 0/40 • From the informed consent form (ICF) signature until the end of the safety follow-up period (7 days after discharge of the subject). The safety was assessed in the safety population, consisting of 166 subjects: 160 randomized subjects (80 in THS 2.2, 40 in CC and 40 in SA) and 6 subjects exposed to THS 2.2 from the product trial on Day -2 but not randomized.	0.00% 0/6 • From the informed consent form (ICF) signature until the end of the safety follow-up period (7 days after discharge of the subject). The safety was assessed in the safety population, consisting of 166 subjects: 160 randomized subjects (80 in THS 2.2, 40 in CC and 40 in SA) and 6 subjects exposed to THS 2.2 from the product trial on Day -2 but not randomized.

Additional Information

Christelle HAZIZA, PhD

Philip Morris Products S.A.

Phone: +41 (58) 242 2625

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee We confirm we have the contractual provisions in place which specifies 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 belongs to the Sponsor.
Publication restrictions are in place

Restriction type: OTHER