Trial Outcomes & Findings for Reduced Exposure Study Using THS 2.2 Menthol With 5 Days in a Confinement Setting and 85 Days in an Ambulatory Setting (NCT NCT01970995)
NCT ID: NCT01970995
Last Updated: 2020-03-23
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
160 participants
Primary outcome timeframe
5 days
Results posted on
2020-03-23
Participant Flow
Study initiated (first subject screened): 01 August 2013 At admission (Day -2), all the subjects performed a product trial of the THS 2.2 Menthol. During the baseline period, they continued smoking their single preferred brand of mCC. Then, on Day 0, they were randomized to one of the 3 study arms (mTHS 2.2, mCC or SA) in a 2:1:1 ratio.
Enrolled and randomized population = 160 subjects * 78 subjects in mTHS 2.2 * 42 subjects in mCC * 40 subjects in SA Number of subjects enrolled but NOT randomized (who tried the mTHS 2.2 at Day -2) = 0
Participant milestones
| Measure |
THS 2.2 Menthol (mTHS 2.2)
Ad libitum use of THS 2.2 Menthol for 5 days in a confinement setting and 85 days in an ambulatory setting
|
Menthol Conventional Cigarette (mCC)
Ad libitum use of subject's own preferred brand of mCC for 5 days in a confinement setting and 85 days in an ambulatory setting
|
Smoking Abstinence (SA)
Abstinence from smoking for 5 days in a confinement setting and 85 days in an ambulatory setting
|
|---|---|---|---|
|
Confinement Period (Population at Day 5)
STARTED
|
78
|
42
|
40
|
|
Confinement Period (Population at Day 5)
COMPLETED
|
77
|
41
|
39
|
|
Confinement Period (Population at Day 5)
NOT COMPLETED
|
1
|
1
|
1
|
|
End of Study (Population at Day 90)
STARTED
|
77
|
41
|
39
|
|
End of Study (Population at Day 90)
COMPLETED
|
76
|
41
|
38
|
|
End of Study (Population at Day 90)
NOT COMPLETED
|
1
|
0
|
1
|
Reasons for withdrawal
| Measure |
THS 2.2 Menthol (mTHS 2.2)
Ad libitum use of THS 2.2 Menthol for 5 days in a confinement setting and 85 days in an ambulatory setting
|
Menthol Conventional Cigarette (mCC)
Ad libitum use of subject's own preferred brand of mCC for 5 days in a confinement setting and 85 days in an ambulatory setting
|
Smoking Abstinence (SA)
Abstinence from smoking for 5 days in a confinement setting and 85 days in an ambulatory setting
|
|---|---|---|---|
|
Confinement Period (Population at Day 5)
Withdrawal by Subject
|
1
|
1
|
1
|
|
End of Study (Population at Day 90)
Withdrawal by Subject
|
1
|
0
|
1
|
Baseline Characteristics
Reduced Exposure Study Using THS 2.2 Menthol With 5 Days in a Confinement Setting and 85 Days in an Ambulatory Setting
Baseline characteristics by cohort
| Measure |
THS 2.2 Menthol (mTHS 2.2)
n=78 Participants
Ad libitum use of THS 2.2 Menthol for 5 days in a confinement setting and 85 days in an ambulatory setting
|
Menthol Conventional Cigarette (mCC)
n=42 Participants
Ad libitum use of subject's own preferred brand of mCC for 5 days in a confinement setting and 85 days in an ambulatory setting
|
Smoking Abstinence (SA)
n=40 Participants
Abstinence from smoking for 5 days in a confinement setting and 85 days in an ambulatory setting
|
Total
n=160 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
37.1 years
STANDARD_DEVIATION 10.58 • n=93 Participants
|
37.4 years
STANDARD_DEVIATION 11.23 • n=4 Participants
|
37.0 years
STANDARD_DEVIATION 9.96 • n=27 Participants
|
37.2 years
STANDARD_DEVIATION 10.54 • n=483 Participants
|
|
Sex: Female, Male
Female
|
33 Participants
n=93 Participants
|
17 Participants
n=4 Participants
|
18 Participants
n=27 Participants
|
68 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
45 Participants
n=93 Participants
|
25 Participants
n=4 Participants
|
22 Participants
n=27 Participants
|
92 Participants
n=483 Participants
|
|
Daily mCC consumption at Screening
10 to 19 cig/day
|
40 participants
n=93 Participants
|
23 participants
n=4 Participants
|
21 participants
n=27 Participants
|
84 participants
n=483 Participants
|
|
Daily mCC consumption at Screening
> 19 cig/day
|
38 participants
n=93 Participants
|
19 participants
n=4 Participants
|
19 participants
n=27 Participants
|
76 participants
n=483 Participants
|
PRIMARY outcome
Timeframe: 5 daysPopulation: The analysis was performed on the Per Protocol set (PP) which included all randomized subjects who had no major protocol deviation impacting the evaluability during the confinement period.
Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics.
Outcome measures
| Measure |
THS 2.2 Menthol (mTHS 2.2)
n=76 Participants
Ad libitum use of THS 2.2 Menthol for 5 days in a confinement setting and 85 days in an ambulatory setting
|
Menthol Conventional Cigarette (mCC)
n=42 Participants
Ad libitum use of subject's own preferred brand of mCC for 5 days in a confinement setting and 85 days in an ambulatory setting
|
Smoking Abstinence (SA)
n=39 Participants
Abstinence from smoking for 5 days in a confinement setting and 85 days in an ambulatory setting
|
|---|---|---|---|
|
Concentration of Monohydroxybutenyl Mercapturic Acid (MHBMA)
|
83.21 pg/mg creat
Interval 73.51 to 94.19
|
617.04 pg/mg creat
Interval 521.87 to 729.55
|
83.57 pg/mg creat
Interval 70.32 to 99.32
|
PRIMARY outcome
Timeframe: 5 daysPopulation: The analysis was performed on the Per Protocol set (PP) which included all randomized subjects who had no major protocol deviation impacting the evaluability during the confinement period.
Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics.
Outcome measures
| Measure |
THS 2.2 Menthol (mTHS 2.2)
n=76 Participants
Ad libitum use of THS 2.2 Menthol for 5 days in a confinement setting and 85 days in an ambulatory setting
|
Menthol Conventional Cigarette (mCC)
n=42 Participants
Ad libitum use of subject's own preferred brand of mCC for 5 days in a confinement setting and 85 days in an ambulatory setting
|
Smoking Abstinence (SA)
n=39 Participants
Abstinence from smoking for 5 days in a confinement setting and 85 days in an ambulatory setting
|
|---|---|---|---|
|
Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA)
|
304.56 ng/mg creat
Interval 283.22 to 327.5
|
601.11 ng/mg creat
Interval 545.07 to 662.91
|
183.61 ng/mg creat
Interval 165.93 to 203.18
|
PRIMARY outcome
Timeframe: 5 daysPopulation: The analysis was performed on the Per Protocol set (PP) which included all randomized subjects who had no major protocol deviation impacting the evaluability during the confinement period.
Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics.
Outcome measures
| Measure |
THS 2.2 Menthol (mTHS 2.2)
n=76 Participants
Ad libitum use of THS 2.2 Menthol for 5 days in a confinement setting and 85 days in an ambulatory setting
|
Menthol Conventional Cigarette (mCC)
n=42 Participants
Ad libitum use of subject's own preferred brand of mCC for 5 days in a confinement setting and 85 days in an ambulatory setting
|
Smoking Abstinence (SA)
n=39 Participants
Abstinence from smoking for 5 days in a confinement setting and 85 days in an ambulatory setting
|
|---|---|---|---|
|
Concentration of S-phenylmercapturic Acid (S-PMA)
|
119.18 pg/mg creat
Interval 107.73 to 131.85
|
1086.89 pg/mg creat
Interval 948.47 to 1245.51
|
104.83 pg/mg creat
Interval 91.07 to 120.66
|
PRIMARY outcome
Timeframe: 5 daysPopulation: The analysis was performed on the Per Protocol set (PP) which included all randomized subjects who had no major protocol deviation impacting the evaluability during the confinement period.
% 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
| Measure |
THS 2.2 Menthol (mTHS 2.2)
n=76 Participants
Ad libitum use of THS 2.2 Menthol for 5 days in a confinement setting and 85 days in an ambulatory setting
|
Menthol Conventional Cigarette (mCC)
n=42 Participants
Ad libitum use of subject's own preferred brand of mCC for 5 days in a confinement setting and 85 days in an ambulatory setting
|
Smoking Abstinence (SA)
n=39 Participants
Abstinence from smoking for 5 days in a confinement setting and 85 days in an ambulatory setting
|
|---|---|---|---|
|
Levels of Carboxyhemoglobin (COHb)
|
2.47 % of saturation of hemoglobin
Interval 2.37 to 2.57
|
5.49 % of saturation of hemoglobin
Interval 5.21 to 5.79
|
2.49 % of saturation of hemoglobin
Interval 2.35 to 2.63
|
PRIMARY outcome
Timeframe: 90 daysPopulation: The analysis was performed on the Per Protocol set (PP) which included all randomized subjects who had no major protocol deviation impacting the evaluability during the period Day 60 to Day 90.
Concentrations measured at Day 90 in urine, adjusted for creatinine. Geometric Least Squares (LS) means are provided as descriptive statistics.
Outcome measures
| Measure |
THS 2.2 Menthol (mTHS 2.2)
n=70 Participants
Ad libitum use of THS 2.2 Menthol for 5 days in a confinement setting and 85 days in an ambulatory setting
|
Menthol Conventional Cigarette (mCC)
n=41 Participants
Ad libitum use of subject's own preferred brand of mCC for 5 days in a confinement setting and 85 days in an ambulatory setting
|
Smoking Abstinence (SA)
n=37 Participants
Abstinence from smoking for 5 days in a confinement setting and 85 days in an ambulatory setting
|
|---|---|---|---|
|
Concentration of Total 4-(Methylnitrosamino)-1-(3- Pyridyl)-1-butanol) (Total NNAL)
|
22.48 pg/mg creat
Interval 18.82 to 26.84
|
96.65 pg/mg creat
Interval 76.63 to 121.9
|
14.90 pg/mg creat
Interval 11.67 to 19.02
|
Adverse Events
THS 2.2 Menthol (mTHS 2.2)
Serious events: 0 serious events
Other events: 16 other events
Deaths: 0 deaths
Menthol Conventional Cigarette (mCC)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Smoking Abstinence (SA)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
THS 2.2 Menthol (mTHS 2.2)
n=78 participants at risk
Ad libitum use of THS 2.2 Menthol for 5 days in a confinement setting and 85 days in an ambulatory setting
|
Menthol Conventional Cigarette (mCC)
n=42 participants at risk
Ad libitum use of subject's own preferred brand of mCC for 5 days in a confinement setting and 85 days in an ambulatory setting
|
Smoking Abstinence (SA)
n=40 participants at risk
Abstinence from smoking for 5 days in a confinement setting and 85 days in an ambulatory setting
|
|---|---|---|---|
|
Investigations
Haemoglobin decreased
|
14.1%
11/78 • Number of events 13 • From the informed consent form signature until the end of the safety follow-up period, up to 150 days (including a screening period of up to 28 days, a 9-day confinement period followed by a 85-day ambulatory setting, and by a 28-day safety follow-up period (28 days after discharge of the subject or early discontinuation)).
The safety was assessed in the safety population, consisting of 160 subjects: 160 randomized subjects (78 in mTHS 2.2, 42 in mCC and 40 in SA) and no subject exposed to mTHS 2.2 from the product trial on Day -2 but not randomized.
|
7.1%
3/42 • Number of events 5 • From the informed consent form signature until the end of the safety follow-up period, up to 150 days (including a screening period of up to 28 days, a 9-day confinement period followed by a 85-day ambulatory setting, and by a 28-day safety follow-up period (28 days after discharge of the subject or early discontinuation)).
The safety was assessed in the safety population, consisting of 160 subjects: 160 randomized subjects (78 in mTHS 2.2, 42 in mCC and 40 in SA) and no subject exposed to mTHS 2.2 from the product trial on Day -2 but not randomized.
|
7.5%
3/40 • Number of events 4 • From the informed consent form signature until the end of the safety follow-up period, up to 150 days (including a screening period of up to 28 days, a 9-day confinement period followed by a 85-day ambulatory setting, and by a 28-day safety follow-up period (28 days after discharge of the subject or early discontinuation)).
The safety was assessed in the safety population, consisting of 160 subjects: 160 randomized subjects (78 in mTHS 2.2, 42 in mCC and 40 in SA) and no subject exposed to mTHS 2.2 from the product trial on Day -2 but not randomized.
|
|
Investigations
Neutrophil count decreased
|
6.4%
5/78 • Number of events 5 • From the informed consent form signature until the end of the safety follow-up period, up to 150 days (including a screening period of up to 28 days, a 9-day confinement period followed by a 85-day ambulatory setting, and by a 28-day safety follow-up period (28 days after discharge of the subject or early discontinuation)).
The safety was assessed in the safety population, consisting of 160 subjects: 160 randomized subjects (78 in mTHS 2.2, 42 in mCC and 40 in SA) and no subject exposed to mTHS 2.2 from the product trial on Day -2 but not randomized.
|
2.4%
1/42 • Number of events 1 • From the informed consent form signature until the end of the safety follow-up period, up to 150 days (including a screening period of up to 28 days, a 9-day confinement period followed by a 85-day ambulatory setting, and by a 28-day safety follow-up period (28 days after discharge of the subject or early discontinuation)).
The safety was assessed in the safety population, consisting of 160 subjects: 160 randomized subjects (78 in mTHS 2.2, 42 in mCC and 40 in SA) and no subject exposed to mTHS 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 signature until the end of the safety follow-up period, up to 150 days (including a screening period of up to 28 days, a 9-day confinement period followed by a 85-day ambulatory setting, and by a 28-day safety follow-up period (28 days after discharge of the subject or early discontinuation)).
The safety was assessed in the safety population, consisting of 160 subjects: 160 randomized subjects (78 in mTHS 2.2, 42 in mCC and 40 in SA) and no subject exposed to mTHS 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