Trial Outcomes & Findings for Nicotine Pharmacokinetic Profile and Safety of the Tobacco Heating System 2.2 (THS 2.2) (NCT NCT01967732)
NCT ID: NCT01967732
Last Updated: 2020-03-17
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 means are provided.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
62 participants
Primary outcome timeframe
3 days
Results posted on
2020-03-17
Participant Flow
Study initiated (first subject screened): 01 November 2013 At admission (Day -1), all the subjects performed a product trial (THS 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 = 62 subjects = 62 randomized as described below: * Sequence "THS 2.2 then CC": 22 subjects * Sequence "CC then THS 2.2": 22 subjects * Sequence "THS 2.2 then NNS": 9 subjects * Sequence "NNS 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 NNS
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 NNS)
|
NNS 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 NNS)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single product use of THS 2.2).
|
|---|---|---|---|---|
|
Washout Period of 1 Day (Day 0)
STARTED
|
22
|
22
|
9
|
9
|
|
Washout Period of 1 Day (Day 0)
COMPLETED
|
22
|
21
|
9
|
9
|
|
Washout Period of 1 Day (Day 0)
NOT COMPLETED
|
0
|
1
|
0
|
0
|
|
First Intervention (Day 1)
STARTED
|
22
|
21
|
9
|
9
|
|
First Intervention (Day 1)
COMPLETED
|
22
|
20
|
9
|
9
|
|
First Intervention (Day 1)
NOT COMPLETED
|
0
|
1
|
0
|
0
|
|
Washout Period of 1 Day (Day 2)
STARTED
|
22
|
20
|
9
|
9
|
|
Washout Period of 1 Day (Day 2)
COMPLETED
|
22
|
20
|
9
|
9
|
|
Washout Period of 1 Day (Day 2)
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
Second Intervention (Day 3)
STARTED
|
22
|
20
|
9
|
9
|
|
Second Intervention (Day 3)
COMPLETED
|
22
|
20
|
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 NNS
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 NNS)
|
NNS 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 NNS)
* Day 2 = wash-out
* Day 3 = 2nd intervention (single product use of THS 2.2).
|
|---|---|---|---|---|
|
Washout Period of 1 Day (Day 0)
Dropped due to personal reasons
|
0
|
1
|
0
|
0
|
|
First Intervention (Day 1)
Poor venous access
|
0
|
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 |
Group 1
n=42 Participants
This population comprises the following sequences:
* Sequence "THS 2.2 then CC"
* Sequence "CC then THS 2.2"
|
Group 2
n=18 Participants
This population comprises the following sequences:
* Sequence "THS 2.2 then NNS"
* Sequence "NNS then THS 2.2"
|
Total
n=60 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
32.1 years
STANDARD_DEVIATION 8.98 • n=99 Participants
|
30.6 years
STANDARD_DEVIATION 5.80 • n=107 Participants
|
31.7 years
STANDARD_DEVIATION 8.13 • n=206 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=99 Participants
|
8 Participants
n=107 Participants
|
25 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
25 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
35 Participants
n=206 Participants
|
|
International Organization for Standardization (ISO) nicotine level
≤ 0.6 mg
|
17 participants
n=99 Participants
|
8 participants
n=107 Participants
|
25 participants
n=206 Participants
|
|
International Organization for Standardization (ISO) nicotine level
> 0.6 to ≤ 1 mg
|
25 participants
n=99 Participants
|
10 participants
n=107 Participants
|
35 participants
n=206 Participants
|
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 |
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 NNS"
* Sequence "NNS then THS 2.2"
|
NNS - 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 NNS"
* Sequence "NNS then THS 2.2"
|
|---|---|---|---|---|
|
Maximum Concentration (Cmax) of Nicotine Following Single Use of THS 2.2, CC and NNS
|
9.62 ng/mL
Interval 8.28 to 11.17
|
12.42 ng/mL
Interval 10.69 to 14.42
|
10.52 ng/mL
Interval 7.91 to 13.98
|
3.51 ng/mL
Interval 2.63 to 4.66
|
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 |
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 NNS"
* Sequence "NNS then THS 2.2"
|
NNS - 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 NNS"
* Sequence "NNS 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 NNS
|
15.10 h*ng/mL
Interval 13.19 to 17.29
|
20.28 h*ng/mL
Interval 17.71 to 23.22
|
17.87 h*ng/mL
Interval 13.79 to 23.15
|
8.02 h*ng/mL
Interval 6.19 to 10.39
|
Adverse Events
Group 1
Serious events: 0 serious events
Other events: 15 other events
Deaths: 0 deaths
Group 2
Serious events: 0 serious events
Other events: 6 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 "THS 2.2 then CC"
* Sequence "CC then THS 2.2"
|
Group 2
n=18 participants at risk
This population comprises the following sequences:
* Sequence "THS 2.2 then NNS"
* Sequence "NNS then THS 2.2"
|
|---|---|---|
|
Nervous system disorders
Dizziness
|
13.6%
6/44 • 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 62 subjects: 44 subjects in Group 1, 18 subjects in Group 2. This population includes all the subjects exposed to THS 2.2 and NNS from the product trials on Day -1.
|
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 62 subjects: 44 subjects in Group 1, 18 subjects in Group 2. This population includes all the subjects exposed to THS 2.2 and NNS from the product trials on Day -1.
|
|
Nervous system disorders
Headache
|
11.4%
5/44 • Number of events 5 • 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 62 subjects: 44 subjects in Group 1, 18 subjects in Group 2. This population includes all the subjects exposed to THS 2.2 and NNS from the product trials on Day -1.
|
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 62 subjects: 44 subjects in Group 1, 18 subjects in Group 2. This population includes all the subjects exposed to THS 2.2 and NNS from the product trials on Day -1.
|
|
Nervous system disorders
Presyncope
|
9.1%
4/44 • Number of events 4 • 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 62 subjects: 44 subjects in Group 1, 18 subjects in Group 2. This population includes all the subjects exposed to THS 2.2 and NNS from the product trials on Day -1.
|
11.1%
2/18 • 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 62 subjects: 44 subjects in Group 1, 18 subjects in Group 2. This population includes all the subjects exposed to THS 2.2 and NNS from the product trials on Day -1.
|
|
Gastrointestinal disorders
Nausea
|
6.8%
3/44 • Number of events 4 • 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 62 subjects: 44 subjects in Group 1, 18 subjects in Group 2. This population includes all the subjects exposed to THS 2.2 and NNS from the product trials on Day -1.
|
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 62 subjects: 44 subjects in Group 1, 18 subjects in Group 2. This population includes all the subjects exposed to THS 2.2 and NNS from the product trials on Day -1.
|
|
Gastrointestinal disorders
Vomiting
|
6.8%
3/44 • Number of events 3 • 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 62 subjects: 44 subjects in Group 1, 18 subjects in Group 2. This population includes all the subjects exposed to THS 2.2 and NNS from the product trials on Day -1.
|
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 62 subjects: 44 subjects in Group 1, 18 subjects in Group 2. This population includes all the subjects exposed to THS 2.2 and NNS from the product trials on Day -1.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
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 62 subjects: 44 subjects in Group 1, 18 subjects in Group 2. This population includes all the subjects exposed to THS 2.2 and NNS from the product trials on Day -1.
|
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 62 subjects: 44 subjects in Group 1, 18 subjects in Group 2. This population includes all the subjects exposed to THS 2.2 and NNS from the product trials on Day -1.
|
|
Vascular disorders
Pallor
|
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 62 subjects: 44 subjects in Group 1, 18 subjects in Group 2. This population includes all the subjects exposed to THS 2.2 and NNS from the product trials on Day -1.
|
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 62 subjects: 44 subjects in Group 1, 18 subjects in Group 2. This population includes all the subjects exposed to THS 2.2 and NNS from the product trials on Day -1.
|
|
Renal and urinary disorders
Haematuria
|
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 62 subjects: 44 subjects in Group 1, 18 subjects in Group 2. This population includes all the subjects exposed to THS 2.2 and NNS from the product trials on Day -1.
|
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 62 subjects: 44 subjects in Group 1, 18 subjects in Group 2. This population includes all the subjects exposed to THS 2.2 and NNS from the product trials on Day -1.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
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 62 subjects: 44 subjects in Group 1, 18 subjects in Group 2. This population includes all the subjects exposed to THS 2.2 and NNS from the product trials on Day -1.
|
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 62 subjects: 44 subjects in Group 1, 18 subjects in Group 2. This population includes all the subjects exposed to THS 2.2 and NNS from the product trials on Day -1.
|
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