Trial Outcomes & Findings for Nicotine Pharmacokinetic Profile and Safety of the Tobacco Heating System 2.2 Menthol (THS 2.2 Menthol) (NCT NCT01967719)
NCT ID: NCT01967719
Last Updated: 2020-03-18
Results Overview
Derived from multiple blood sampling on Day 1 and Day 3 (1 blood sampling pre-product use and multiple blood sampling over 24 hours post-product use). Geometric Least Squares (geometric LS) means are provided.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
64 participants
Primary outcome timeframe
3 days
Results posted on
2020-03-18
Participant Flow
Study initiated (first subject screened): 02 October 2013 At admission (Day -1), all the subjects performed a product trial (mTHS 2.2 and subsequently NNS). From enrollment, they were asked to remain abstinent from smoking for at least 24 hours (Day 0) before being randomized on Day 1 into 1 of the 4 sequences.
Enrolled population = 64 subjects: 2 exposed to mTHS 2.2 and NNS at Admission but not randomized and 62 randomized as described below: * Sequence "mTHS 2.2 then mCC": 22 subjects * Sequence "mCC then mTHS 2.2": 22 subjects * Sequence "mTHS 2.2 then NNS": 9 subjects * Sequence "NNS then mTHS 2.2": 9 subjects
Participant milestones
| Measure |
mTHS 2.2 Then mCC
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single product use of mTHS 2.2)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single product use of mCC).
|
mCC Then mTHS 2.2
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single product use of mCC)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single product use of mTHS 2.2).
|
mTHS 2.2 Then NNS
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single product use of mTHS 2.2)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single administration of NNS)
|
NNS Then mTHS 2.2
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single administration of NNS)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single product use of mTHS 2.2).
|
|---|---|---|---|---|
|
Washout Period of 1 Day (Day 0)
STARTED
|
22
|
22
|
9
|
9
|
|
Washout Period of 1 Day (Day 0)
COMPLETED
|
22
|
22
|
9
|
9
|
|
Washout Period of 1 Day (Day 0)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
First Intervention (Day 1)
STARTED
|
22
|
22
|
9
|
9
|
|
First Intervention (Day 1)
COMPLETED
|
22
|
21
|
9
|
8
|
|
First Intervention (Day 1)
NOT COMPLETED
|
0
|
1
|
0
|
1
|
|
Washout Period of 1 Day (Day 2)
STARTED
|
22
|
21
|
9
|
8
|
|
Washout Period of 1 Day (Day 2)
COMPLETED
|
22
|
21
|
9
|
8
|
|
Washout Period of 1 Day (Day 2)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Second Intervention (Day 3)
STARTED
|
22
|
21
|
9
|
8
|
|
Second Intervention (Day 3)
COMPLETED
|
22
|
20
|
9
|
8
|
|
Second Intervention (Day 3)
NOT COMPLETED
|
0
|
1
|
0
|
0
|
Reasons for withdrawal
| Measure |
mTHS 2.2 Then mCC
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single product use of mTHS 2.2)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single product use of mCC).
|
mCC Then mTHS 2.2
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single product use of mCC)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single product use of mTHS 2.2).
|
mTHS 2.2 Then NNS
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single product use of mTHS 2.2)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single administration of NNS)
|
NNS Then mTHS 2.2
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single administration of NNS)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single product use of mTHS 2.2).
|
|---|---|---|---|---|
|
First Intervention (Day 1)
Withdrawal by Subject
|
0
|
1
|
0
|
1
|
|
Second Intervention (Day 3)
Withdrawal by Subject
|
0
|
1
|
0
|
0
|
Baseline Characteristics
Nicotine Pharmacokinetic Profile and Safety of the Tobacco Heating System 2.2 Menthol (THS 2.2 Menthol)
Baseline characteristics by cohort
| Measure |
Group 1
n=41 Participants
This population comprises the following sequences:
* Sequence "mTHS 2.2 then mCC"
* Sequence "mCC then mTHS 2.2"
|
Group 2
n=17 Participants
This population comprises the following sequences:
* Sequence "mTHS 2.2 then NNS"
* Sequence "NNS then mTHS 2.2"
|
Total
n=58 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
36.7 years
STANDARD_DEVIATION 9.68 • n=5 Participants
|
33.8 years
STANDARD_DEVIATION 6.93 • n=7 Participants
|
35.9 years
STANDARD_DEVIATION 9.00 • n=5 Participants
|
|
Sex: Female, Male
Female
|
20 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
21 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
International Organization for Standardization (ISO) nicotine yield
≤ 1.0 mg
|
21 participants
n=5 Participants
|
11 participants
n=7 Participants
|
32 participants
n=5 Participants
|
|
International Organization for Standardization (ISO) nicotine yield
> 1.0 mg
|
20 participants
n=5 Participants
|
6 participants
n=7 Participants
|
26 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 daysPopulation: Pharmacokinetics (PK) populations consisted of all the randomized subjects who completed at least 1 of the single use days (Days 1 or 3), and for whom at least 1 PK parameter could be derived. Subjects with major protocol deviations that impacted the evaluability of the results were excluded from the PK populations.
Derived from multiple blood sampling on Day 1 and Day 3 (1 blood sampling pre-product use and multiple blood sampling over 24 hours post-product use). Geometric Least Squares (geometric LS) means are provided.
Outcome measures
| Measure |
mTHS 2.2 - Group 1
n=41 Participants
The geometric least squares mean presented below takes into consideration the data of the subjects who were randomized in the following sequences:
* Sequence "mTHS 2.2 then mCC"
* Sequence "mCC then mTHS 2.2"
|
mCC - Group 1
n=41 Participants
The geometric least squares mean presented below takes into consideration the data of the subjects who were randomized in the following sequences:
* Sequence "mTHS 2.2 then mCC"
* Sequence "mCC then mTHS 2.2"
|
mTHS 2.2 - Group 2
n=17 Participants
The geometric least squares mean presented below takes into consideration the data of the subjects who were randomized in the following sequences:
* Sequence "mTHS 2.2 then NNS"
* Sequence "NNS then mTHS 2.2"
|
NNS - Group 2
n=17 Participants
The geometric least squares mean presented below takes into consideration the data of the subjects who were randomized in the following sequences:
* Sequence "mTHS 2.2 then NNS"
* Sequence "NNS then mTHS 2.2"
|
|---|---|---|---|---|
|
Maximum Concentration (Cmax) of Nicotine Following Single Use of mTHS 2.2, mCC and NNS
|
7.40 ng/mL
Interval 6.21 to 8.82
|
13.08 ng/mL
Interval 10.99 to 15.58
|
8.40 ng/mL
Interval 6.17 to 11.43
|
3.23 ng/mL
Interval 2.37 to 4.4
|
PRIMARY outcome
Timeframe: 3 daysPopulation: PK populations consisted of all the randomized subjects who completed at least 1 of the single use days (Days 1 or 3), and for whom at least 1 PK parameter could be derived. Subjects with major protocol deviations that impacted the evaluability of the results were excluded from the PK populations.
Derived from multiple blood sampling on Day 1 and Day 3 (1 blood sampling pre-product use and multiple blood sampling over 24 hours post-product use). Geometric Least Squares means are provided.
Outcome measures
| Measure |
mTHS 2.2 - Group 1
n=41 Participants
The geometric least squares mean presented below takes into consideration the data of the subjects who were randomized in the following sequences:
* Sequence "mTHS 2.2 then mCC"
* Sequence "mCC then mTHS 2.2"
|
mCC - Group 1
n=41 Participants
The geometric least squares mean presented below takes into consideration the data of the subjects who were randomized in the following sequences:
* Sequence "mTHS 2.2 then mCC"
* Sequence "mCC then mTHS 2.2"
|
mTHS 2.2 - Group 2
n=17 Participants
The geometric least squares mean presented below takes into consideration the data of the subjects who were randomized in the following sequences:
* Sequence "mTHS 2.2 then NNS"
* Sequence "NNS then mTHS 2.2"
|
NNS - Group 2
n=17 Participants
The geometric least squares mean presented below takes into consideration the data of the subjects who were randomized in the following sequences:
* Sequence "mTHS 2.2 then NNS"
* Sequence "NNS then mTHS 2.2"
|
|---|---|---|---|---|
|
Area Under the Plasma Nicotine Concentration-Time Curve From Time Zero (Pre-product Use) to Last Time Point [AUC(0-last)] Following Single Use of mTHS 2.2, mCC and NNS
|
16.53 h*ng/mL
Interval 13.84 to 19.74
|
29.71 h*ng/mL
Interval 24.88 to 35.47
|
15.59 h*ng/mL
Interval 10.8 to 22.49
|
8.72 h*ng/mL
Interval 6.04 to 12.58
|
Adverse Events
Group 1
Serious events: 0 serious events
Other events: 12 other events
Deaths: 0 deaths
Group 2
Serious events: 0 serious events
Other events: 5 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
| Measure |
Group 1
n=44 participants at risk
This population comprises the following sequences:
* Sequence "mTHS 2.2 then mCC"
* Sequence "mCC then mTHS 2.2"
|
Group 2
n=18 participants at risk
This population comprises the following sequences:
* Sequence "mTHS 2.2 then NNS"
* Sequence "NNS then mTHS 2.2"
|
Enrolled But Not Randomized
n=2 participants at risk
Subjects who tried the mTHS 2.2 at Admission (Day -1) but were not randomized in 1 of the 2 groups as they were back-up subjects
|
|---|---|---|---|
|
Nervous system disorders
Headache
|
15.9%
7/44 • Number of events 7 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
0.00%
0/18 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
0.00%
0/2 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
|
Nervous system disorders
Dizziness
|
2.3%
1/44 • Number of events 1 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
5.6%
1/18 • Number of events 1 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
0.00%
0/2 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
|
Gastrointestinal disorders
Vomiting
|
4.5%
2/44 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
5.6%
1/18 • Number of events 1 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
0.00%
0/2 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
|
Gastrointestinal disorders
Nausea
|
2.3%
1/44 • Number of events 1 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
5.6%
1/18 • Number of events 1 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
0.00%
0/2 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/44 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
5.6%
1/18 • Number of events 1 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
0.00%
0/2 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
4.5%
2/44 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
5.6%
1/18 • Number of events 1 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
0.00%
0/2 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
|
Skin and subcutaneous tissue disorders
Rash
|
2.3%
1/44 • Number of events 1 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
5.6%
1/18 • Number of events 1 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
0.00%
0/2 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
|
Eye disorders
Eye pruritus
|
0.00%
0/44 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
5.6%
1/18 • Number of events 1 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
0.00%
0/2 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
|
Eye disorders
Ocular hyperaemia
|
0.00%
0/44 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
5.6%
1/18 • Number of events 1 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
0.00%
0/2 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
|
Infections and infestations
Upper respiratory tract infection
|
0.00%
0/44 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
5.6%
1/18 • Number of events 1 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 but not randomized.
|
0.00%
0/2 • 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 64 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 2 subjects exposed to mTHS 2.2 and NNS from the product trials on Day -1 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