Trial Outcomes & Findings for Nicotine Pharmacokinetic Profile and Safety of the Tobacco Heating System 2.2 (THS 2.2) (NCT NCT01959607)
NCT ID: NCT01959607
Last Updated: 2025-01-16
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.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
65 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 T0
Results posted on
2025-01-16
Participant Flow
Study initiated (first subject screened): 31 July 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 one of four product use sequences.
Enrolled population = 65 subjects: 3 subjects exposed to THS 2.2 and NRT gum at Admission but not randomized and 62 randomized to one of the four product use sequences described below: * Product Use Sequence "THS 2.2 then CC": 22 subjects * Product Use Sequence "CC then THS 2.2": 22 subjects * Product Use Sequence "THS 2.2 then NRT": 9 subjects * Product Use Sequence "NRT then THS 2.2": 9 subjects
Participant milestones
| Measure |
THS 2.2 Then CC
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single product use of THS 2.2)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single product use of CC).
|
CC Then THS 2.2
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single product use of CC)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single product use of THS 2.2).
|
THS 2.2 Then NRT
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single product use of THS 2.2)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single administration of NRT gum \[Nicorette ® 2mg\]).
|
NRT Then THS 2.2
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single administration of NRT gum \[Nicorette ® 2mg\])
* Day 2 = wash-out
* Day 3 = 2nd intervention (single product use of THS 2.2).
|
|---|---|---|---|---|
|
Washout Period of 24 Hrs. (Day 0)
STARTED
|
22
|
22
|
9
|
9
|
|
Washout Period of 24 Hrs. (Day 0)
COMPLETED
|
22
|
22
|
9
|
9
|
|
Washout Period of 24 Hrs. (Day 0)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
First Intervention (Day 1)
STARTED
|
22
|
22
|
9
|
9
|
|
First Intervention (Day 1)
COMPLETED
|
21
|
21
|
9
|
9
|
|
First Intervention (Day 1)
NOT COMPLETED
|
1
|
1
|
0
|
0
|
|
Washout Period of 24 Hrs. (Day 2)
STARTED
|
21
|
21
|
9
|
9
|
|
Washout Period of 24 Hrs. (Day 2)
COMPLETED
|
21
|
21
|
9
|
9
|
|
Washout Period of 24 Hrs. (Day 2)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Second Intervention (Day 3)
STARTED
|
21
|
21
|
9
|
9
|
|
Second Intervention (Day 3)
COMPLETED
|
21
|
21
|
9
|
9
|
|
Second Intervention (Day 3)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
THS 2.2 Then CC
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single product use of THS 2.2)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single product use of CC).
|
CC Then THS 2.2
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single product use of CC)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single product use of THS 2.2).
|
THS 2.2 Then NRT
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single product use of THS 2.2)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single administration of NRT gum \[Nicorette ® 2mg\]).
|
NRT Then THS 2.2
Each subject will follow the below study design:
* Day 0 = Wash-out (1 day)
* Day 1 = 1st intervention (single administration of NRT gum \[Nicorette ® 2mg\])
* Day 2 = wash-out
* Day 3 = 2nd intervention (single product use of THS 2.2).
|
|---|---|---|---|---|
|
First Intervention (Day 1)
Withdrawal by Subject
|
1
|
1
|
0
|
0
|
Baseline Characteristics
Nicotine Pharmacokinetic Profile and Safety of the Tobacco Heating System 2.2 (THS 2.2)
Baseline characteristics by cohort
| Measure |
THS 2.2 - CC
n=22 Participants
This population was randomized to the following product use sequence:
"THS 2.2 then CC"
|
CC -THS 2.2
n=22 Participants
This population was randomized to the following product use sequence:
"CC then THS 2.2"
|
THS 2.2 - NRT
n=9 Participants
This population was randomized to the following product use sequence:
"THS 2.2 then NRT"
|
NRT - THS 2.2
n=9 Participants
This population was randomized to the following product use sequence:
"NRT then THS 2.2"
|
Enrolled But Not Randomized
n=3 Participants
This population comprised enrolled subjects who tried the THS 2.2 at Admission (Day -1) but were not randomized to a product use sequence.
|
Total
n=65 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Customized
Between 23 and 65 years
|
32.9 years
STANDARD_DEVIATION 7.56 • n=5 Participants
|
32.7 years
STANDARD_DEVIATION 9.84 • n=7 Participants
|
34.7 years
STANDARD_DEVIATION 12.36 • n=5 Participants
|
36.9 years
STANDARD_DEVIATION 8.71 • n=4 Participants
|
42.7 years
STANDARD_DEVIATION 11.85 • n=21 Participants
|
34.1 years
STANDARD_DEVIATION 9.45 • n=8 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
34 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
5 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
31 Participants
n=8 Participants
|
|
International Organization for Standardization (ISO) nicotine level
≤ 0.6 mg
|
14 participants
n=5 Participants
|
8 participants
n=7 Participants
|
6 participants
n=5 Participants
|
4 participants
n=4 Participants
|
0 participants
n=21 Participants
|
32 participants
n=8 Participants
|
|
International Organization for Standardization (ISO) nicotine level
> 0.6 to ≤ 1 mg
|
8 participants
n=5 Participants
|
14 participants
n=7 Participants
|
3 participants
n=5 Participants
|
5 participants
n=4 Participants
|
3 participants
n=21 Participants
|
33 participants
n=8 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 |
THS 2.2 - Group 1
n=42 Participants
The geometric least squares mean presented below takes into consideration the data of the subjects who were randomized in the following sequences:
* Sequence "THS 2.2 then CC"
* Sequence "CC then THS 2.2"
|
CC - Group 1
n=42 Participants
The geometric least squares mean presented below takes into consideration the data of the subjects who were randomized in the following sequences:
* Sequence "THS 2.2 then CC"
* Sequence "CC then THS 2.2"
|
THS 2.2 - 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 "THS 2.2 then NRT"
* Sequence "NRT then THS 2.2"
|
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 "THS 2.2 then NRT"
* Sequence "NRT then THS 2.2"
|
|---|---|---|---|---|
|
Maximum Concentration (Cmax) of Nicotine Following Single Use of THS 2.2, CC and NRT
|
14.30 ng/mL
Interval 12.43 to 16.45
|
13.82 ng/mL
Interval 12.01 to 15.89
|
11.53 ng/mL
Interval 7.49 to 17.74
|
4.80 ng/mL
Interval 3.11 to 7.39
|
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 |
THS 2.2 - Group 1
n=42 Participants
The geometric least squares mean presented below takes into consideration the data of the subjects who were randomized in the following sequences:
* Sequence "THS 2.2 then CC"
* Sequence "CC then THS 2.2"
|
CC - Group 1
n=42 Participants
The geometric least squares mean presented below takes into consideration the data of the subjects who were randomized in the following sequences:
* Sequence "THS 2.2 then CC"
* Sequence "CC then THS 2.2"
|
THS 2.2 - 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 "THS 2.2 then NRT"
* Sequence "NRT then THS 2.2"
|
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 "THS 2.2 then NRT"
* Sequence "NRT then THS 2.2"
|
|---|---|---|---|---|
|
Area Under the Plasma Concentration-Time Curve From Time Zero (Pre-product Use) to Last Time Point [AUC(0-last)] Following Single Use of THS 2.2, CC and NRT
|
23.75 ng*h/mL
Interval 21.76 to 25.94
|
24.66 ng*h/mL
Interval 22.58 to 26.92
|
18.92 ng*h/mL
Interval 13.3 to 26.91
|
14.88 ng*h/mL
Interval 10.46 to 21.17
|
Adverse Events
THS 2.2 Use
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
CC Use
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
NRT Gum Use
Serious events: 0 serious events
Other events: 2 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 |
THS 2.2 Use
n=44 participants at risk
This population used THS 2.2 as part of their randomized product use sequence
|
CC Use
n=44 participants at risk
This population used CC as part of their randomized product use sequence
|
NRT Gum Use
n=18 participants at risk
This population used NRT Gum as part of their randomized product use sequence
|
Enrolled But Not Randomized
n=3 participants at risk
This population comprised enrolled subjects who tried the THS 2.2 at Admission (Day -1) but were not randomized to a product use sequence.
|
|---|---|---|---|---|
|
Psychiatric disorders
Dysphoria
|
2.3%
1/44 • 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 population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
2.3%
1/44 • 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 population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
0.00%
0/18 • From informed consent form (ICF) signature until the end of the safety follow-up period (7 days after discharge of the subject)
The safety population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
0.00%
0/3 • From informed consent form (ICF) signature until the end of the safety follow-up period (7 days after discharge of the subject)
The safety population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
|
Psychiatric disorders
Tobacco withdrawal symptoms
|
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 population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
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 population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
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 population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
0.00%
0/3 • From informed consent form (ICF) signature until the end of the safety follow-up period (7 days after discharge of the subject)
The safety population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
|
Nervous system disorders
Tension headache
|
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 population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
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 population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
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 population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
0.00%
0/3 • From informed consent form (ICF) signature until the end of the safety follow-up period (7 days after discharge of the subject)
The safety population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
|
Nervous system disorders
Dizziness
|
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 population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
2.3%
1/44 • 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 population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
0.00%
0/18 • From informed consent form (ICF) signature until the end of the safety follow-up period (7 days after discharge of the subject)
The safety population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
0.00%
0/3 • From informed consent form (ICF) signature until the end of the safety follow-up period (7 days after discharge of the subject)
The safety population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
|
Nervous system disorders
Nervous system disorder
|
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 population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
2.3%
1/44 • 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 population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
0.00%
0/18 • From informed consent form (ICF) signature until the end of the safety follow-up period (7 days after discharge of the subject)
The safety population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
0.00%
0/3 • From informed consent form (ICF) signature until the end of the safety follow-up period (7 days after discharge of the subject)
The safety population consisted of 65 subjects (62 randomized subjects and 3 subjects exposed to THS 2.2 and NRT gum during the product trial on Day -1 but not randomized). Adverse events were reported according to the product use sequence and intervention. Adverse events by intervention are reported here.
|
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