Trial Outcomes & Findings for Nicotine Pharmacokinetic Profile and Safety of the Tobacco Heating System 2.2 Menthol (THS 2.2 Menthol). (NCT NCT01967706)
NCT ID: NCT01967706
Last Updated: 2020-03-18
Results Overview
T0 = start of single product use. 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.
COMPLETED
NA
73 participants
Blood taken 15 minutes prior to T0, 2, 4, 6, 8, 10, 15, 30, 45 minutes, 1, 2, 4, 6, 9, 12, and 24 hours after T0
2020-03-18
Participant Flow
Study initiated (first subject screened): 01 August 2013 At admission (Day -1), all the subjects performed a product trial (Tobacco Sticks and subsequently NRT gum). 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 = 73 subjects: 11 exposed to mTHS and NRT at Admission but not randomized and 62 randomized as described below: * Sequence "mTHS then mCC": 22 subjects * Sequence "mCC then mTHS": 22 subjects * Sequence "mTHS then NRT": 9 subjects * Sequence "NRT then mTHS": 9 subjects
Participant milestones
| Measure |
mTHS 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)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single product use of mCC).
|
mCC Then mTHS
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).
|
mTHS Then NRT
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single product use of mTHS)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single administration of NRT)
|
NRT Then mTHS
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single administration of NRT)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single product use of mTHS).
|
|---|---|---|---|---|
|
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
|
21
|
22
|
9
|
9
|
|
First Intervention (Day 1)
NOT COMPLETED
|
1
|
0
|
0
|
0
|
|
Washout Period of 1 Day (Day 2)
STARTED
|
21
|
22
|
9
|
9
|
|
Washout Period of 1 Day (Day 2)
COMPLETED
|
21
|
22
|
9
|
9
|
|
Washout Period of 1 Day (Day 2)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Second Intervention (Day 3)
STARTED
|
21
|
22
|
9
|
9
|
|
Second Intervention (Day 3)
COMPLETED
|
21
|
22
|
9
|
9
|
|
Second Intervention (Day 3)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
mTHS 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)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single product use of mCC).
|
mCC Then mTHS
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).
|
mTHS Then NRT
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single product use of mTHS)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single administration of NRT)
|
NRT Then mTHS
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single administration of NRT)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single product use of mTHS).
|
|---|---|---|---|---|
|
First Intervention (Day 1)
Withdrawal by Subject
|
1
|
0
|
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=43 Participants
This population comprises the following sequences:
* Sequence "mTHS then mCC"
* Sequence "mCC then mTHS"
|
Group 2
n=18 Participants
This population comprises the following sequences:
* Sequence "mTHS then NRT"
* Sequence "NRT then mTHS"
|
Total
n=61 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Customized
Between 23 and 65 years
|
33.4 years
STANDARD_DEVIATION 10.03 • n=5 Participants
|
30.7 years
STANDARD_DEVIATION 7.80 • n=7 Participants
|
32.6 years
STANDARD_DEVIATION 9.44 • 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
|
23 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
International Organization for Standardization (ISO) nicotine level
≤ 0.6 mg
|
25 participants
n=5 Participants
|
10 participants
n=7 Participants
|
35 participants
n=5 Participants
|
|
International Organization for Standardization (ISO) nicotine level
> 0.6 to ≤ 1 mg
|
18 participants
n=5 Participants
|
8 participants
n=7 Participants
|
26 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Blood taken 15 minutes prior to T0, 2, 4, 6, 8, 10, 15, 30, 45 minutes, 1, 2, 4, 6, 9, 12, and 24 hours after T0Population: 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.
T0 = start of single product use. 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 - Group 1
n=43 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 then mCC"
* Sequence "mCC then mTHS"
|
mCC - Group 1
n=43 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 then mCC"
* Sequence "mCC then mTHS"
|
mTHS - Group 2
n=18 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 then NRT"
* Sequence "NRT then mTHS"
|
NRT - Group 2
n=18 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 then NRT"
* Sequence "NRT then mTHS"
|
|---|---|---|---|---|
|
Maximum Concentration (Cmax) of Nicotine Following Single Use of mTHS, mCC and NRT
|
10.70 ng/mL
Interval 8.94 to 12.8
|
12.09 ng/mL
Interval 10.1 to 14.47
|
7.64 ng/mL
Interval 5.39 to 10.81
|
7.52 ng/mL
Interval 5.31 to 10.64
|
PRIMARY outcome
Timeframe: Blood taken 15 minutes prior to T0, 2, 4, 6, 8, 10, 15, 30, 45 minutes, 1, 2, 4, 6, 9, 12, and 24 hours after T0Population: 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.
T0 = start of single product use. 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 - Group 1
n=43 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 then mCC"
* Sequence "mCC then mTHS"
|
mCC - Group 1
n=43 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 then mCC"
* Sequence "mCC then mTHS"
|
mTHS - Group 2
n=18 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 then NRT"
* Sequence "NRT then mTHS"
|
NRT - Group 2
n=18 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 then NRT"
* Sequence "NRT then mTHS"
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time Zero (Pre-product Use) to Last Time Point [AUC(0-last)] Following Single Use of mTHS, mCC and NRT
|
23.99 ng*h/mL
Interval 20.87 to 27.57
|
24.45 ng*h/mL
Interval 21.27 to 28.1
|
15.61 ng*h/mL
Interval 11.96 to 20.37
|
27.94 ng*h/mL
Interval 21.41 to 36.45
|
Adverse Events
Group 1
Group 2
Enrolled But Not Randomized
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Group 1
n=44 participants at risk
This population comprised the subjects that followed these intervention sequences:
* Sequence "mTHS then mCC"
* Sequence "mCC then mTHS"
|
Group 2
n=18 participants at risk
This population comprised the subjects that followed these intervention sequences:
* Sequence "mTHS then NRT"
* Sequence "NRT then mTHS"
|
Enrolled But Not Randomized
n=11 participants at risk
Subjects who tried the mTHS at Admission (Day -1) but were not randomized in 1 of the 2 groups as they were back-up subjects
|
|---|---|---|---|
|
Investigations
Hemoglobin decreased
|
0.00%
0/44 • From 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 73 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 11 subjects exposed to mTHS and NRT from the product trials on Day -1 but not randomized.
|
5.6%
1/18 • Number of events 1 • From 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 73 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 11 subjects exposed to mTHS and NRT from the product trials on Day -1 but not randomized.
|
0.00%
0/11 • From 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 73 subjects: 62 randomized subjects (44 in Group 1, 18 in Group 2) and 11 subjects exposed to mTHS and NRT from the product trials on Day -1 but not randomized.
|
Additional Information
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