Evaluation of Biological and Functional Changes in Healthy Smokers After Switching to THS 2.2 for 26 Weeks
Study Details
Study Description
Brief Summary
The aim of the study is to demonstrate clinical, biological and functional health changes in smokers switching to the candidate modified risk tobacco product: Tobacco Heating System 2.2 (THS 2.2) as compared to smokers continuing smoking their conventional cigarettes (CC) over a 26-week period.
To characterize the study as successful, at least 5 clinical risk endpoints should move in the direction of smoking cessation and these results would be statistically significant. The main analysis will be defined a priori (using the Hailperin-Ruger approach) and will be made between THS 2.2 use and CC use as "per actual product used" and product use categories.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
N/A |
Detailed Description
The clinical, biological and functional endpoints to be measured in this study ("smoker's health profile") may characterize the modification of risk of smoking-related diseases.
Clinical risk endpoint to be assessed are selected based on a) their association to smoking-related diseases b) their association to smoking status, c) their reversibility upon smoking cessation, and d) their suitability to be measured with valid and robust methods in clinical studies.
The biological markers, functional markers and biomarkers of exposure (BoExp) with the strongest scientific evidence will constitute the 'smoker's health profile' and will be measured as the primary objective of the study.
Additional endpoints involved in the mechanistic of smoking-related diseases will be studied to provide additional scientific evidence to strengthen the primary objective.
The study will provide a perspective of product usage in a "real world setting" where smoking CC in addition to THS 2.2 may be expected.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: THS 2.2 Ad libitum use of THS 2.2 |
Other: THS 2.2
Ad libitum use of THS 2.2 in an ambulatory setting for 26 weeks
|
Active Comparator: CC Ad libitum use of CC |
Other: CC
Ad libitum use of CC in an ambulatory setting for 26 weeks
|
Outcome Measures
Primary Outcome Measures
- Levels of High Density Lipoprotein C (HDL-C). [26 Weeks]
Concentrations measured in serum. Geometric Least Squares means are provided as descriptive statistics.
- Levels of White Blood Cells (WBC). [26 Weeks]
Concentrations measured in blood. Geometric Least Squares means are provided as descriptive statistics.
- Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1). [26 Weeks]
FEV1 post-bronchodilator and expressed as percentage predicted (FEV1 %pred). Geometric Least Squares means are provided as descriptive statistics.
- Concentrations of Soluble Intercellular Adhesion Molecule 1 (sICAM-1). [26 Weeks]
Concentrations measured in serum. Geometric Least Squares means are provided as descriptive statistics.
- Concentrations of 11-dehydrothromboxane B2 (11-DTXB2). [26 Weeks]
Concentrations measured in urine and expressed as concentration adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics.
- Concentrations of 8-epi-prostaglandin F2α (8-epi-PGF2α). [26 Weeks]
Concentrations measured in urine and expressed as concentration adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics.
- Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL). [26 Weeks]
Concentrations measured in urine and expressed as concentration adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics.
- Percent Change From Baseline of Carboxyhemoglobin (COHb) [26 Weeks]
Carboxyhemoglobin (COHb) is assayed from whole blood. Geometric Least Squares means are provided as descriptive statistics. Expressed as % of saturation of hemoglobin.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Current healthy smoker as judged by the Principal Investigator(s) or designee(s)
-
Minimum age: 30 years old
-
Have smoked for the last 10 years
-
Have smoked more than 10 non menthol CC/day on average (no brand restriction) over the past year
Exclusion Criteria:
-
Clinically relevant medical conditions that in the opinion of the investigators would jeopardize the safety of the participant.
-
Subject who has (FEV1/FVC) < 0.7 and FEV1 < 80% predicted value at post-bronchodilator spirometry
-
Subject with asthma condition (post-bronchodilator FEV1/FVC < 0.75 and reversibility in FEV1 ≥ 12% and > 200 mL from pre- to post-bronchodilator values)
-
Subject who took or is taking concomitant medication which may have an impact on the "smoker's heath profile"
-
Female subject is pregnant or breast feeding.
-
Female subject who does not agree to use an acceptable method of effective contraception.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Celerion Arizona | Tempe | Arizona | United States | 85283 |
2 | Clinical Research West Florida | Clearwater | Florida | United States | 33765 |
3 | Covance, Inc | Daytona Beach | Florida | United States | 32117 |
4 | Compass Research | Orlando | Florida | United States | 32806 |
5 | Clinical Research West Florida | Tampa | Florida | United States | 33603 |
6 | Compass Research | The Villages | Florida | United States | 32162 |
7 | Central Kentucky Research Associate | Lexington | Kentucky | United States | 40509 |
8 | Celerion Lincoln | Lincoln | Nebraska | United States | 68502 |
9 | PMG Research of Cary | Cary | North Carolina | United States | 27518 |
10 | PMG Research of Charlotte | Charlotte | North Carolina | United States | 28209 |
11 | PMG Research of Raleigh | Raleigh | North Carolina | United States | 27609 |
12 | PMG Research of Wilmington | Wilmington | North Carolina | United States | 28401 |
13 | Midwest Clinical Research Center | Dayton | Ohio | United States | 45417 |
14 | PMG Research of Bristol | Bristol | Tennessee | United States | 37620 |
15 | NOCCR | Knoxville | Tennessee | United States | 37920 |
16 | Benchmark | Austin | Texas | United States | 78705 |
17 | Benchmark | Fort Worth | Texas | United States | 76135 |
18 | Benchmark | San Angelo | Texas | United States | 76904 |
19 | National Clinical Research | Richmond | Virginia | United States | 23294 |
Sponsors and Collaborators
- Philip Morris Products S.A.
Investigators
- Study Chair: Christelle Haziza, PhD, Philip Morris Products S.A.
- Principal Investigator: Danielle Armas, MD, Celerion Arizona
- Principal Investigator: Leonard Dunn, MD, Clinical Research West Florida
- Principal Investigator: Hugh Coleman, MD, Covance
- Principal Investigator: George Stoica, MD, Compass Research
- Principal Investigator: Mark Adams, MD, Central Kentucky Research Associate
- Principal Investigator: Peter Davidson, MD, Celerion Lincoln
- Principal Investigator: John Rubino, MD, PMG Research of Raleigh
- Principal Investigator: George Raad, MD, PMG Research of Charlotte
- Principal Investigator: Kevin Cannon, MD, PMG Research of Wilmington
- Principal Investigator: Derek Schroder, MD, PMG Research of Cary
- Principal Investigator: Stephanie Powell, MD, PMG Research of Bristol
- Principal Investigator: William Smith, MD, NOCCR
- Principal Investigator: Darrell Herrington, MD, Benchmark
- Principal Investigator: Laurence Chu, MD, Benchmark
- Principal Investigator: William Seger, MD, Benchmark
- Principal Investigator: Lon Lynn, MD, Clinical Research West Florida
- Principal Investigator: David Subich, MD, Compass Research
- Principal Investigator: Isabel Kuhare-Arcure, MD, Midwest Clinical Research
- Principal Investigator: Keith Scott, MD, National Clinical Research
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ZRHR-ERS-09-US
- ZRHR-ERS-09-US
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | Following randomization of 984 subjects, from 1039 enrolled subjects, one clinical site was terminated from this study due to non-GCP compliance. The safety population of 1012 subjects included all enrolled subjects except 27 subjects from the terminated site. |
Arm/Group Title | THS 2.2 Group | CC Group |
---|---|---|
Arm/Group Description | Randomized to Ad libitum use of THS 2.2 in an ambulatory setting for 26 weeks | Randomized to Ad libitum use of CC in an ambulatory setting for 26 weeks |
Period Title: Overall Study | ||
STARTED | 488 | 496 |
Full Analysis Set - As Exposed (FAS-EX) | 414 | 443 |
COMPLETED | 381 | 422 |
NOT COMPLETED | 107 | 74 |
Baseline Characteristics
Arm/Group Title | THS 2.2 Use | CC Use | Dual Use | Other Use | Total |
---|---|---|---|---|---|
Arm/Group Description | ≥1 THS 2.2 or CC, and ≥70% THS 2.2 use over the analysis period, and ≥70% THS 2.2 use on >50% of days in the analysis period. | ≥1 THS 2.2 or CC use, and <1% THS 2.2 use over the entire analysis period and <1% THS 2.2 use on ≥ 50% of days in the analysis period. | ≥ 1 THS 2.2 or CC and, 1% ≤THS 2.2 <70% over the analysis period, or THS 2.2-use and CC-use categories do not apply to 50% of these days. | Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns between consecutive analysis periods. | Total of all reporting groups |
Overall Participants | 245 | 428 | 142 | 42 | 857 |
Age (years) [Mean (Standard Deviation) ] | |||||
Mean (Standard Deviation) [years] |
44.2
(9.64)
|
45.2
(9.55)
|
43.8
(9.77)
|
44.2
(8.14)
|
44.6
(9.55)
|
Sex: Female, Male (Count of Participants) | |||||
Female |
94
38.4%
|
182
42.5%
|
63
44.4%
|
14
33.3%
|
353
41.2%
|
Male |
151
61.6%
|
246
57.5%
|
79
55.6%
|
28
66.7%
|
504
58.8%
|
Ethnicity (NIH/OMB) (Count of Participants) | |||||
Hispanic or Latino |
17
6.9%
|
28
6.5%
|
7
4.9%
|
1
2.4%
|
53
6.2%
|
Not Hispanic or Latino |
228
93.1%
|
400
93.5%
|
135
95.1%
|
41
97.6%
|
804
93.8%
|
Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Race (NIH/OMB) (Count of Participants) | |||||
American Indian or Alaska Native |
2
0.8%
|
2
0.5%
|
2
1.4%
|
0
0%
|
6
0.7%
|
Asian |
2
0.8%
|
5
1.2%
|
0
0%
|
1
2.4%
|
8
0.9%
|
Native Hawaiian or Other Pacific Islander |
1
0.4%
|
2
0.5%
|
0
0%
|
0
0%
|
3
0.4%
|
Black or African American |
42
17.1%
|
74
17.3%
|
25
17.6%
|
10
23.8%
|
151
17.6%
|
White |
195
79.6%
|
341
79.7%
|
113
79.6%
|
30
71.4%
|
679
79.2%
|
More than one race |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Unknown or Not Reported |
3
1.2%
|
4
0.9%
|
2
1.4%
|
1
2.4%
|
10
1.2%
|
BMI (kg/m2) [Mean (Standard Deviation) ] | |||||
Mean (Standard Deviation) [kg/m2] |
26.9
(3.99)
|
27.1
(4.13)
|
26.9
(4.35)
|
26.9
(5.12)
|
27.0
(4.18)
|
Outcome Measures
Title | Levels of High Density Lipoprotein C (HDL-C). |
---|---|
Description | Concentrations measured in serum. Geometric Least Squares means are provided as descriptive statistics. |
Time Frame | 26 Weeks |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set - As Exposed (FAS-EX) |
Arm/Group Title | THS 2.2 Use | CC Use | Dual Use | Other Use |
---|---|---|---|---|
Arm/Group Description | ≥1 THS 2.2 or CC, and ≥70% THS 2.2 use over the analysis period, and ≥70% THS 2.2 use on >50% of days in the analysis period. | ≥1 THS 2.2 or CC use, and <1% THS 2.2 use over the entire analysis period and <1% THS 2.2 use on ≥ 50% of days in the analysis period. | ≥ 1 THS 2.2 or CC and, 1% ≤THS 2.2 <70% over the analysis period, or THS 2.2-use and CC-use categories do not apply to 50% of these days. | Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns between consecutive analysis periods. |
Measure Participants | 245 | 428 | 142 | 42 |
Geometric Mean (95% Confidence Interval) [mg/dL] |
54.1
|
50.9
|
56.3
|
52.8
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | THS 2.2 Use, CC Use |
---|---|---|
Comments | The analysis will test if the mean level of HDL-C for THS-use is greater than for CC-use. The following hypothesis will be evaluated: H0: XTHS - XCC ≤ 0.0 HA: XTHS - XCC > 0.0 where XTHS and XCC are the adjusted means of THS-use and CC-use, respectively. H0 is rejected with a type I error α = 1.5625% (one-sided test). | |
Type of Statistical Test | Other | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.001 |
Comments | ||
Method | Hailperin-Rüger | |
Comments | p-value less than 1.5625% would be considered statistically significant, following test multiplicity adjustment using the Hailperin-Rüger approach | |
Method of Estimation | Estimation Parameter | LS Mean Difference |
Estimated Value | 3.09 | |
Confidence Interval |
(2-Sided) 96.875% 1.10 to 5.09 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Levels of White Blood Cells (WBC). |
---|---|
Description | Concentrations measured in blood. Geometric Least Squares means are provided as descriptive statistics. |
Time Frame | 26 Weeks |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set - As Exposed (FAS-EX) |
Arm/Group Title | THS 2.2 Use | CC Use | Dual Use | Other Use |
---|---|---|---|---|
Arm/Group Description | ≥1 THS 2.2 or CC, and ≥70% THS 2.2 use over the analysis period, and ≥70% THS 2.2 use on >50% of days in the analysis period. | ≥1 THS 2.2 or CC use, and <1% THS 2.2 use over the entire analysis period and <1% THS 2.2 use on ≥ 50% of days in the analysis period. | ≥ 1 THS 2.2 or CC and, 1% ≤THS 2.2 <70% over the analysis period, or THS 2.2-use and CC-use categories do not apply to 50% of these days. | Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns between consecutive analysis periods. |
Measure Participants | 245 | 428 | 142 | 42 |
Geometric Mean (95% Confidence Interval) [GI/L] |
6.98
|
7.48
|
7.41
|
8.71
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | THS 2.2 Use, CC Use |
---|---|---|
Comments | The analysis will test if the mean level of WBC for THS-use is lower than for CC-use. The following hypothesis will be evaluated: H0: XTHS - XCC ≥ 0.0 HA: XTHS - XCC < 0.0 where XTHS and XCC are the adjusted means of THS-use and CC-use, respectively. H0 is rejected with a type I error α = 1.5625% (one-sided test). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.001 |
Comments | ||
Method | Hailperin-Rüger | |
Comments | p-value less than 1.5625% would be considered statistically significant, following test multiplicity adjustment using the Hailperin-Rüger approach | |
Method of Estimation | Estimation Parameter | LS Mean Difference |
Estimated Value | -0.420 | |
Confidence Interval |
(2-Sided) 96.875% -0.717 to -0.123 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1). |
---|---|
Description | FEV1 post-bronchodilator and expressed as percentage predicted (FEV1 %pred). Geometric Least Squares means are provided as descriptive statistics. |
Time Frame | 26 Weeks |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set - As Exposed (FAS-EX) |
Arm/Group Title | THS 2.2 Use | CC Use | Dual Use | Other Use |
---|---|---|---|---|
Arm/Group Description | ≥1 THS 2.2 or CC, and ≥70% THS 2.2 use over the analysis period, and ≥70% THS 2.2 use on >50% of days in the analysis period. | ≥1 THS 2.2 or CC use, and <1% THS 2.2 use over the entire analysis period and <1% THS 2.2 use on ≥ 50% of days in the analysis period. | ≥ 1 THS 2.2 or CC and, 1% ≤THS 2.2 <70% over the analysis period, or THS 2.2-use and CC-use categories do not apply to 50% of these days. | Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns between consecutive analysis periods. |
Measure Participants | 245 | 428 | 142 | 42 |
Geometric Mean (95% Confidence Interval) [Percent of predicted FEV1] |
95.4
|
93.4
|
93.7
|
94.3
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | THS 2.2 Use, CC Use |
---|---|---|
Comments | The analysis will test if the mean level of FEV1 for THS-use is greater than for CC-use. The following hypothesis will be evaluated: H0: XTHS - XCC ≤ 0.0 HA: XTHS - XCC > 0.0 where XTHS and XCC are the adjusted means of THS-use and CC-use, respectively. H0 is rejected with a type I error α = 1.5625% (one-sided test). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.008 |
Comments | ||
Method | Hailperin-Rüger | |
Comments | p-value less than 1.5625% would be considered statistically significant, following test multiplicity adjustment using the Hailperin-Rüger approach | |
Method of Estimation | Estimation Parameter | LS Mean Difference |
Estimated Value | 1.28 | |
Confidence Interval |
(2-Sided) 96.875% 0.145 to 2.42 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Concentrations of Soluble Intercellular Adhesion Molecule 1 (sICAM-1). |
---|---|
Description | Concentrations measured in serum. Geometric Least Squares means are provided as descriptive statistics. |
Time Frame | 26 Weeks |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set - As Exposed (FAS-EX) |
Arm/Group Title | THS 2.2 Use | CC Use | Dual Use | Other Use |
---|---|---|---|---|
Arm/Group Description | ≥1 THS 2.2 or CC, and ≥70% THS 2.2 use over the analysis period, and ≥70% THS 2.2 use on >50% of days in the analysis period. | ≥1 THS 2.2 or CC use, and <1% THS 2.2 use over the entire analysis period and <1% THS 2.2 use on ≥ 50% of days in the analysis period. | ≥ 1 THS 2.2 or CC and, 1% ≤THS 2.2 <70% over the analysis period, or THS 2.2-use and CC-use categories do not apply to 50% of these days. | Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns between consecutive analysis periods. |
Measure Participants | 245 | 428 | 142 | 42 |
Geometric Mean (95% Confidence Interval) [ng/mL] |
252
|
266
|
270
|
273
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | THS 2.2 Use, CC Use |
---|---|---|
Comments | The analysis of sICAM-1 will test if the mean level of this clinical risk endpoint for THS-use is lower relative to CC-use. The following hypothesis will be evaluated: H0: XTHS / XCC ≥ 1.0 HA: XTHS / XCC < 1.0 where XTHS and XCC are the adjusted geometrical means of THS-use and CC-use, respectively. H0 is rejected with a type I error α = 1.5625% (one-sided test). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.030 |
Comments | ||
Method | Hailperin-Rüger | |
Comments | p-value less than 1.5625% would be considered statistically significant, following test multiplicity adjustment using the Hailperin-Rüger approach | |
Method of Estimation | Estimation Parameter | % Reduction |
Estimated Value | 2.86 | |
Confidence Interval |
(2-Sided) 96.875% -0.426 to 6.04 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Derived as 1 - LS Mean Ratio (THS / CC) |
Title | Concentrations of 11-dehydrothromboxane B2 (11-DTXB2). |
---|---|
Description | Concentrations measured in urine and expressed as concentration adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics. |
Time Frame | 26 Weeks |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set - As Exposed (FAS-EX) |
Arm/Group Title | THS 2.2 Use | CC Use | Dual Use | Other Use |
---|---|---|---|---|
Arm/Group Description | ≥1 THS 2.2 or CC, and ≥70% THS 2.2 use over the analysis period, and ≥70% THS 2.2 use on >50% of days in the analysis period. | ≥1 THS 2.2 or CC use, and <1% THS 2.2 use over the entire analysis period and <1% THS 2.2 use on ≥ 50% of days in the analysis period. | ≥ 1 THS 2.2 or CC and, 1% ≤THS 2.2 <70% over the analysis period, or THS 2.2-use and CC-use categories do not apply to 50% of these days. | Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns between consecutive analysis periods. |
Measure Participants | 245 | 428 | 142 | 42 |
Geometric Mean (95% Confidence Interval) [pg/mg creat] |
496
|
523
|
532
|
626
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | THS 2.2 Use, CC Use |
---|---|---|
Comments | The analysis of 11-DTX-B2 will test if the mean level of this clinical risk endpoint for THS-use is lower relative to CC-use. The following hypothesis will be evaluated: H0: XTHS / XCC ≥ 1.0 HA: XTHS / XCC < 1.0 where XTHS and XCC are the adjusted geometrical means of THS-use and CC-use, respectively. H0 is rejected with a type I error α = 1.5625% (one-sided test). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.193 |
Comments | ||
Method | Hailperin-Rüger | |
Comments | p-value less than 1.5625% would be considered statistically significant, following test multiplicity adjustment using the Hailperin-Rüger approach | |
Method of Estimation | Estimation Parameter | % Reduction |
Estimated Value | 4.74 | |
Confidence Interval |
(2-Sided) 96.875% -7.5 to 15.6 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Derived as 1 - LS Mean Ratio (THS / CC) |
Title | Concentrations of 8-epi-prostaglandin F2α (8-epi-PGF2α). |
---|---|
Description | Concentrations measured in urine and expressed as concentration adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics. |
Time Frame | 26 Weeks |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set - As Exposed (FAS-EX) |
Arm/Group Title | THS 2.2 Use | CC Use | Dual Use | Other Use |
---|---|---|---|---|
Arm/Group Description | ≥1 THS 2.2 or CC, and ≥70% THS 2.2 use over the analysis period, and ≥70% THS 2.2 use on >50% of days in the analysis period. | ≥1 THS 2.2 or CC use, and <1% THS 2.2 use over the entire analysis period and <1% THS 2.2 use on ≥ 50% of days in the analysis period. | ≥ 1 THS 2.2 or CC and, 1% ≤THS 2.2 <70% over the analysis period, or THS 2.2-use and CC-use categories do not apply to 50% of these days. | Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns between consecutive analysis periods. |
Measure Participants | 245 | 428 | 142 | 42 |
Geometric Mean (95% Confidence Interval) [pg/mg creat] |
321
|
351
|
347
|
335
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | THS 2.2 Use, CC Use |
---|---|---|
Comments | The analysis of 8-epi-PGF2α will test if the mean level of this clinical risk endpoint for THS-use is lower relative to CC-use. The following hypothesis will be evaluated: H0: XTHS / XCC ≥ 1.0 HA: XTHS / XCC < 1.0 where XTHS and XCC are the adjusted geometrical means of THS-use and CC-use, respectively. H0 is rejected with a type I error α = 1.5625% (one-sided test). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | 0.018 |
Comments | ||
Method | Hailperin-Rüger | |
Comments | p-value less than 1.5625% would be considered statistically significant, following test multiplicity adjustment using the Hailperin-Rüger approach | |
Method of Estimation | Estimation Parameter | % Reduction |
Estimated Value | 6.80 | |
Confidence Interval |
(2-Sided) 96.875% -0.216 to 13.3 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Derived as 1 - LS Mean Ratio (THS / CC) |
Title | Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL). |
---|---|
Description | Concentrations measured in urine and expressed as concentration adjusted for creatinine. Geometric Least Squares means are provided as descriptive statistics. |
Time Frame | 26 Weeks |
Outcome Measure Data
Analysis Population Description |
---|
Full Analysis Set - As Exposed (FAS-EX) |
Arm/Group Title | THS 2.2 Use | CC Use | Dual Use | Other Use |
---|---|---|---|---|
Arm/Group Description | ≥1 THS 2.2 or CC, and ≥70% THS 2.2 use over the analysis period, and ≥70% THS 2.2 use on >50% of days in the analysis period. | ≥1 THS 2.2 or CC use, and <1% THS 2.2 use over the entire analysis period and <1% THS 2.2 use on ≥ 50% of days in the analysis period. | ≥ 1 THS 2.2 or CC and, 1% ≤THS 2.2 <70% over the analysis period, or THS 2.2-use and CC-use categories do not apply to 50% of these days. | Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns between consecutive analysis periods. |
Measure Participants | 245 | 428 | 142 | 42 |
Geometric Mean (95% Confidence Interval) [pg/mg creat] |
144
|
282
|
286
|
342
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | THS 2.2 Use, CC Use |
---|---|---|
Comments | The analysis of Total NNAL will test if the mean level of this clinical risk endpoint for THS-use is lower relative to CC-use. The following hypothesis will be evaluated: H0: XTHS / XCC ≥ 1.0 HA: XTHS / XCC < 1.0 where XTHS and XCC are the adjusted geometrical means of THS-use and CC-use, respectively. H0 is rejected with a type I error α = 1.5625% (one-sided test). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.001 |
Comments | ||
Method | Hailperin-Rüger | |
Comments | p-value less than 1.5625% would be considered statistically significant, following test multiplicity adjustment using the Hailperin-Rüger approach | |
Method of Estimation | Estimation Parameter | % Reduction |
Estimated Value | 43.5 | |
Confidence Interval |
(2-Sided) 96.875% 33.7 to 51.9 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Derived as 1 - LS Mean Ratio (THS / CC) |
Title | Percent Change From Baseline of Carboxyhemoglobin (COHb) |
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Description | Carboxyhemoglobin (COHb) is assayed from whole blood. Geometric Least Squares means are provided as descriptive statistics. Expressed as % of saturation of hemoglobin. |
Time Frame | 26 Weeks |
Outcome Measure Data
Analysis Population Description |
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Full Analysis Set - As Exposed (FAS-EX) |
Arm/Group Title | THS 2.2 Use | CC Use | Dual Use | Other Use |
---|---|---|---|---|
Arm/Group Description | ≥1 THS 2.2 or CC, and ≥70% THS 2.2 use over the analysis period, and ≥70% THS 2.2 use on >50% of days in the analysis period. | ≥1 THS 2.2 or CC use, and <1% THS 2.2 use over the entire analysis period and <1% THS 2.2 use on ≥ 50% of days in the analysis period. | ≥ 1 THS 2.2 or CC and, 1% ≤THS 2.2 <70% over the analysis period, or THS 2.2-use and CC-use categories do not apply to 50% of these days. | Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns between consecutive analysis periods. |
Measure Participants | 245 | 428 | 142 | 42 |
Geometric Mean (95% Confidence Interval) [percentage change from baseline] |
2.84
|
4.38
|
4.23
|
5.59
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | THS 2.2 Use, CC Use |
---|---|---|
Comments | The analysis will test if the mean level of COHb for THS-use is lower relative to CC-use. The following hypothesis will be evaluated: H0: XTHS / XCC ≥ 1.0 HA: XTHS / XCC < 1.0 where XTHS and XCC are the adjusted geometrical means of THS-use and CC-use. H0 is rejected with a type I error α = 1.5625% (one-sided test). | |
Type of Statistical Test | Superiority | |
Comments | ||
Statistical Test of Hypothesis | p-Value | <0.001 |
Comments | ||
Method | Hailperin-Rüger | |
Comments | p-value less than 1.5625% would be considered statistically significant, following test multiplicity adjustment using the Hailperin-Rüger approach | |
Method of Estimation | Estimation Parameter | % Reduction |
Estimated Value | 32.2 | |
Confidence Interval |
(2-Sided) 96.875% 24.5 to 39 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | Derived as 1 - LS Mean Ratio (THS / CC) |
Adverse Events
Time Frame | The entire study duration per subject was between 32 to 38 weeks, including a Screening period of up to 42 days prior to enrollment, a 6 to 10-day run-in period prior to randomization, followed by a 26 week randomized exposure period. The end of study for a subject was defined as the check-out or the date of early termination of the subject plus the 28 day Safety Follow-up period, unless the subject was lost to follow-up. | |||||
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Adverse Event Reporting Description | ||||||
Arm/Group Title | THS 2.2 Group | CC Group | Product Test | |||
Arm/Group Description | Randomized to Ad libitum use of THS 2.2 in an ambulatory setting for 26 weeks | Randomized to Ad libitum use of CC in an ambulatory setting for 26 weeks | Enrolled subjects who participated in a product test, but were not randomized. | |||
All Cause Mortality |
||||||
THS 2.2 Group | CC Group | Product Test | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 2/477 (0.4%) | 0/483 (0%) | 0/52 (0%) | |||
Serious Adverse Events |
||||||
THS 2.2 Group | CC Group | Product Test | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 6/477 (1.3%) | 7/483 (1.4%) | 0/52 (0%) | |||
Infections and infestations | ||||||
Pneumonia mycoplasmal | 1/477 (0.2%) | 1 | 0/483 (0%) | 0 | 0/52 (0%) | 0 |
Cellulitis | 0/477 (0%) | 0 | 1/483 (0.2%) | 1 | 0/52 (0%) | 0 |
Pyelonephritis acute, with Urosepsis and Nephrolithiasis | 0/477 (0%) | 0 | 1/483 (0.2%) | 3 | 0/52 (0%) | 0 |
Tooth Infection | 0/477 (0%) | 0 | 1/483 (0.2%) | 1 | 0/52 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||
Head injury with seizure | 1/477 (0.2%) | 2 | 0/483 (0%) | 0 | 0/52 (0%) | 0 |
Laceration | 1/477 (0.2%) | 1 | 0/483 (0%) | 0 | 0/52 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||
Vertebral osteophyte with Cervical myelopathy | 0/477 (0%) | 0 | 1/483 (0.2%) | 2 | 0/52 (0%) | 0 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
Papillary thyroid cancer | 0/477 (0%) | 0 | 1/483 (0.2%) | 1 | 0/52 (0%) | 0 |
Metastases to small intestine with anaemia | 1/477 (0.2%) | 2 | 0/483 (0%) | 0 | 0/52 (0%) | 0 |
Psychiatric disorders | ||||||
Completed suicide | 1/477 (0.2%) | 1 | 0/483 (0%) | 0 | 0/52 (0%) | 0 |
Suicidal ideation | 0/477 (0%) | 0 | 1/483 (0.2%) | 1 | 0/52 (0%) | 0 |
Alcohol abuse | 1/477 (0.2%) | 1 | 0/483 (0%) | 0 | 0/52 (0%) | 0 |
Adjustment disorder with depressed mood and bereavement | 0/477 (0%) | 0 | 1/483 (0.2%) | 2 | 0/52 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||||
THS 2.2 Group | CC Group | Product Test | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 23/477 (4.8%) | 29/483 (6%) | 0/52 (0%) | |||
Infections and infestations | ||||||
Upper respiratory tract infection | 23/477 (4.8%) | 26 | 29/483 (6%) | 33 | 0/52 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
We confirm we have the contractual provisions in place which specify 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 belong to the Sponsor.
Results Point of Contact
Name/Title | Christelle Haziza |
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Organization | Philip Morris Products S.A. |
Phone | +41 58 242 11 11 |
ClinicalTrials.PMI@pmi.com |
- ZRHR-ERS-09-US
- ZRHR-ERS-09-US