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A 26-week Extension of the ZRHR-ERS-09-US Study Evaluating Biological and Functional Changes in Healthy Smokers After Switching to THS 2.2

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02649556
Recruitment Status : Completed
First Posted : January 7, 2016
Results First Posted : December 4, 2020
Last Update Posted : December 4, 2020
Sponsor:
Information provided by (Responsible Party):
Philip Morris Products S.A.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Other
Condition Smoking
Interventions Other: THS 2.2
Other: CC
Enrollment 672
Recruitment Details Of the 984 subjects (488 in the THS arm and 496 in the CC arm) who were enrolled and randomized into the original study, NCT02396381, 672 subjects were enrolled into the extension study (309 in the THS arm and 363 in the CC arm).
Pre-assignment Details 672 subjects enrolled in the extension study; the 857 subjects in the Full Analysis Set - As Exposed (FAS-EX) included subjects for combined analyses from the original six month study who did not enter the extension study. The analysis was performed according to subjects' exposure over the 12 month period as detailed in "Arm/Group" (Reporting Groups) table.
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use
Hide Arm/Group Description This reporting group comprised 230 subjects. The "THS 2.2 use" product use category was defined as THS use of 70% or more over the entire analysis period. (≥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.) This reporting group comprised 424 subjects. The "CC use" product use category was defined as THS use of less than 1% over the entire 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.) This reporting group comprised 152 subjects. The "Dual use" product use category was defined as THS use of less than 70% over the entire 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.) This reporting group comprised 51 subjects. "Other use" refers to any other product use over the entire analysis period. (Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns.)
Period Title: Overall Study
Started 230 424 152 51
Completed 167 312 102 28
Not Completed 63 112 50 23
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use Total
Hide Arm/Group Description

The "THS 2.2 use" product use category was defined as THS use of 70% or more over the entire analysis period.

(≥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.)

The "CC use" product use category was defined as THS use of less than 1% over the entire 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.)

The "Dual use" product use category was defined as THS use of less than 70% over the entire 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.)

"Other use" refers to any other product use over the entire analysis period. (Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns.) Total of all reporting groups
Overall Number of Baseline Participants 230 424 152 51 857
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 230 participants 424 participants 152 participants 51 participants 857 participants
43.8  (9.68) 45.2  (9.54) 44.2  (9.76) 44.5  (8.21) 44.6  (9.55)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 230 participants 424 participants 152 participants 51 participants 857 participants
Female
87
  37.8%
180
  42.5%
67
  44.1%
19
  37.3%
353
  41.2%
Male
143
  62.2%
244
  57.5%
85
  55.9%
32
  62.7%
504
  58.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 230 participants 424 participants 152 participants 51 participants 857 participants
Hispanic or Latino
17
   7.4%
28
   6.6%
6
   3.9%
2
   3.9%
53
   6.2%
Not Hispanic or Latino
213
  92.6%
396
  93.4%
146
  96.1%
49
  96.1%
804
  93.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 230 participants 424 participants 152 participants 51 participants 857 participants
American Indian or Alaska Native
1
   0.4%
2
   0.5%
2
   1.3%
1
   2.0%
6
   0.7%
Asian
2
   0.9%
5
   1.2%
0
   0.0%
1
   2.0%
8
   0.9%
Native Hawaiian or Other Pacific Islander
1
   0.4%
2
   0.5%
0
   0.0%
0
   0.0%
3
   0.4%
Black or African American
41
  17.8%
73
  17.2%
25
  16.4%
12
  23.5%
151
  17.6%
White
182
  79.1%
338
  79.7%
123
  80.9%
36
  70.6%
679
  79.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
3
   1.3%
4
   0.9%
2
   1.3%
1
   2.0%
10
   1.2%
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 230 participants 424 participants 152 participants 51 participants 857 participants
27.0  (4.06) 27.1  (4.13) 26.9  (4.25) 26.6  (4.91) 27.0  (4.18)
1.Primary Outcome
Title Levels of High Density Lipoprotein C (HDL-C).
Hide Description Concentrations (mg/dL) measured in serum. Mean values are provided as descriptive statistics.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set - As Exposed Analysis (FAS-EX). Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use
Hide Arm/Group Description:

The "THS 2.2 use" product use category was defined as THS use of 70% or more over the entire analysis period.

(≥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.)

The "CC use" product use category was defined as THS use of less than 1% over the entire 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.)

The "Dual use" product use category was defined as THS use of less than 70% over the entire 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.)

"Other use" refers to any other product use over the entire analysis period. (Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns.)
Overall Number of Participants Analyzed 168 315 103 28
Mean (95% Confidence Interval)
Unit of Measure: mg/dL
52.2
(49.5 to 54.8)
50.6
(48.9 to 52.3)
54.0
(49.7 to 58.4)
54.7
(49.2 to 60.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection THS 2.2 Use, CC Use
Comments The analysis will determine the effect of THS 2.2 compared to CC at Month 12 on the components of the "smokers' health profile". This study has no formal pre-specified hypotheses associated with the study objectives. Estimates of THS 2.2 effect will be presented by mean of LS Mean difference of HDL-C levels between CC and THS 2.2 and related 95% CI.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 1.75
Confidence Interval (2-Sided) 95%
-0.160 to 3.65
Estimation Comments [Not Specified]
Other Statistical Analysis Mixed model conducted on original values with visit, baseline value and its interaction with visit, sex, Caucasian origin, product use pattern category and its interaction with visit, and other baseline covariates relevant for the specific clinical risk endpoint as fixed effect factors and site as a random effect.
2.Primary Outcome
Title Levels of White Blood Cells (WBC).
Hide Description Total count in blood (GI/L). Mean values are provided as descriptive statistics.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set - As Exposed Analysis (FAS-EX). Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use
Hide Arm/Group Description:

The "THS 2.2 use" product use category was defined as THS use of 70% or more over the entire analysis period.

(≥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.)

The "CC use" product use category was defined as THS use of less than 1% over the entire 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.)

The "Dual use" product use category was defined as THS use of less than 70% over the entire 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.)

"Other use" refers to any other product use over the entire analysis period. (Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns.)
Overall Number of Participants Analyzed 167 312 102 28
Mean (95% Confidence Interval)
Unit of Measure: GI/L
6.73
(6.47 to 6.99)
7.31
(7.07 to 7.54)
7.28
(6.85 to 7.71)
7.57
(6.85 to 8.29)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection THS 2.2 Use, CC Use
Comments The analysis will determine the effect of THS 2.2 compared to CC at Month 12 on the components of the "smokers' health profile". This study has no formal pre-specified hypotheses associated with the study objectives. Estimates of THS 2.2 effect will be presented by mean of LS Mean difference of White Blood Cell counts between CC and THS 2.2 and related 95% CI.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.413
Confidence Interval (2-Sided) 95%
-0.694 to -0.131
Estimation Comments [Not Specified]
Other Statistical Analysis Mixed model conducted on original values with visit, baseline value and its interaction with visit, sex, Caucasian origin, product use pattern category and its interaction with visit, and other baseline covariates relevant for the specific clinical risk endpoint as fixed effect factors and site as a random effect.
3.Primary Outcome
Title Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1).
Hide Description FEV1 post-bronchodilator and expressed as percentage predicted (FEV1 %pred). Mean values are provided as descriptive statistics.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set - As Exposed Analysis (FAS-EX). Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use
Hide Arm/Group Description:

The "THS 2.2 use" product use category was defined as THS use of 70% or more over the entire analysis period.

(≥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.)

The "CC use" product use category was defined as THS use of less than 1% over the entire 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.)

The "Dual use" product use category was defined as THS use of less than 70% over the entire 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.)

"Other use" refers to any other product use over the entire analysis period. (Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns.)
Overall Number of Participants Analyzed 153 288 95 27
Mean (95% Confidence Interval)
Unit of Measure: Percent of predicted FEV1
93.2
(91.1 to 95.2)
92.3
(90.7 to 94.0)
91.1
(88.2 to 94.1)
95.2
(90.1 to 100)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection THS 2.2 Use, CC Use
Comments The analysis will determine the effect of THS 2.2 compared to CC at Month 12 on the components of the "smokers' health profile". This study has no formal pre-specified hypotheses associated with the study objectives. Estimates of THS 2.2 effect will be presented by mean of LS Mean difference of FEV1 levels between CC and THS 2.2 and related 95% CI.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.914
Confidence Interval (2-Sided) 95%
-0.339 to 2.17
Estimation Comments [Not Specified]
Other Statistical Analysis Mixed model conducted on original values with visit, baseline value and its interaction with visit, sex, Caucasian origin, product use pattern category and its interaction with visit, and other baseline covariates relevant for the specific clinical risk endpoint as fixed effect factors and site as a random effect.
4.Primary Outcome
Title Concentrations of Soluble Intercellular Adhesion Molecule 1 (sICAM-1).
Hide Description Concentrations (ng/mL) measured in serum. Geometric Mean values are provided as descriptive statistics.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set - As Exposed Analysis (FAS-EX). Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use
Hide Arm/Group Description:

The "THS 2.2 use" product use category was defined as THS use of 70% or more over the entire analysis period.

(≥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.)

The "CC use" product use category was defined as THS use of less than 1% over the entire 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.)

The "Dual use" product use category was defined as THS use of less than 70% over the entire 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.)

"Other use" refers to any other product use over the entire analysis period. (Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns.)
Overall Number of Participants Analyzed 168 315 103 28
Geometric Mean (95% Confidence Interval)
Unit of Measure: ng/mL
246
(230 to 263)
258
(244 to 272)
269
(252 to 286)
255
(222 to 292)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection THS 2.2 Use, CC Use
Comments The analysis will determine the effect of THS 2.2 compared to CC at Month 12 on the components of the "smokers' health profile". This study has no formal pre-specified hypotheses associated with the study objectives. Estimates of THS 2.2 effect will be presented by mean of relative reduction of sICAM-1 levels between CC and THS 2.2 and related 95% CI.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter % Relative Reduction
Estimated Value 3.11
Confidence Interval (2-Sided) 95%
0.0231 to 6.10
Estimation Comments Derived as 100 x (1 - Geometric LS Mean Ratio)
Other Statistical Analysis Mixed model conducted on log-transformed values with visit, log-transformed baseline value and its interaction with visit, sex, Caucasian origin, product use pattern category and its interaction with visit, and other baseline covariates relevant for the specific clinical risk endpoint as fixed effect factors and site as a random effect
5.Primary Outcome
Title Concentrations of 11-dehydrothromboxane B2 (11-DTXB2).
Hide Description Concentrations measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat). Geometric Mean values are provided as descriptive statistics.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set - As Exposed Analysis (FAS-EX). Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use
Hide Arm/Group Description:

The "THS 2.2 use" product use category was defined as THS use of 70% or more over the entire analysis period.

(≥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.)

The "CC use" product use category was defined as THS use of less than 1% over the entire 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.)

The "Dual use" product use category was defined as THS use of less than 70% over the entire 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.)

"Other use" refers to any other product use over the entire analysis period. (Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns.)
Overall Number of Participants Analyzed 166 312 102 27
Geometric Mean (95% Confidence Interval)
Unit of Measure: pg/mg creat
582
(518 to 654)
586
(538 to 638)
595
(510 to 693)
536
(396 to 727)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection THS 2.2 Use, CC Use
Comments The analysis will determine the effect of THS 2.2 compared to CC at Month 12 on the components of the "smokers' health profile". This study has no formal pre-specified hypotheses associated with the study objectives. Estimates of THS 2.2 effect will be presented by mean of relative reduction of 11-DTXB2 levels between CC and THS 2.2 and related 95% CI.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter % Relative Reduction
Estimated Value 3.44
Confidence Interval (2-Sided) 95%
-8.74 to 14.3
Estimation Comments Derived as 100 x (1-Geometric LS Mean Ratio)
Other Statistical Analysis Mixed model conducted on log-transformed values with visit, log-transformed baseline value and its interaction with visit, sex, Caucasian origin, product use pattern category and its interaction with visit, and other baseline covariates relevant for the specific clinical risk endpoint as fixed effect factors and site as a random effect
6.Primary Outcome
Title Concentrations of 8-epi-prostaglandin F2α (8-epi-PGF2α).
Hide Description Concentrations measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat). Geometric Mean values are provided as descriptive statistics.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set - As Exposed Analysis (FAS-EX). Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use
Hide Arm/Group Description:

The "THS 2.2 use" product use category was defined as THS use of 70% or more over the entire analysis period.

(≥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.)

The "CC use" product use category was defined as THS use of less than 1% over the entire 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.)

The "Dual use" product use category was defined as THS use of less than 70% over the entire 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.)

"Other use" refers to any other product use over the entire analysis period. (Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns.)
Overall Number of Participants Analyzed 167 312 102 27
Geometric Mean (95% Confidence Interval)
Unit of Measure: pg/mg creat
307
(279 to 338)
327
(307 to 348)
326
(293 to 362)
364
(289 to 458)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection THS 2.2 Use, CC Use
Comments The analysis will determine the effect of THS 2.2 compared to CC at Month 12 on the components of the "smokers' health profile". This study has no formal pre-specified hypotheses associated with the study objectives. Estimates of THS 2.2 effect will be presented by mean of relative reduction of 8-epi-PGF2α levels between CC and THS 2.2 and related 95% CI.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter % Relative Reduction
Estimated Value 7.15
Confidence Interval (2-Sided) 95%
-1.03 to 14.7
Estimation Comments Derived as 100 x (1 - Geometric LS Mean Ratio)
Other Statistical Analysis Mixed model conducted on log-transformed values with visit, log-transformed baseline value and its interaction with visit, sex, Caucasian origin, product use pattern category and its interaction with visit, and other baseline covariates relevant for the specific clinical risk endpoint as fixed effect factors and site as a random effect.
7.Primary Outcome
Title Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL).
Hide Description Concentrations measured in urine and expressed as concentration adjusted for creatinine (pg/mg creat). Geometric Mean values are provided as descriptive statistics.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set - As Exposed Analysis (FAS-EX). Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use
Hide Arm/Group Description:

The "THS 2.2 use" product use category was defined as THS use of 70% or more over the entire analysis period.

(≥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.)

The "CC use" product use category was defined as THS use of less than 1% over the entire 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.)

The "Dual use" product use category was defined as THS use of less than 70% over the entire 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.)

"Other use" refers to any other product use over the entire analysis period. (Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns.)
Overall Number of Participants Analyzed 167 312 102 27
Geometric Mean (95% Confidence Interval)
Unit of Measure: pg/mg creat
133
(105 to 168)
269
(238 to 305)
253
(207 to 309)
304
(214 to 431)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection THS 2.2 Use, CC Use
Comments The analysis will determine the effect of THS 2.2 compared to CC at Month 12 on the components of the "smokers' health profile". This study has no formal pre-specified hypotheses associated with the study objectives. Estimates of THS 2.2 effect will be presented by mean of relative reduction of Total NNAL levels between CC and THS 2.2 and related 95% CI.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter % Relative Reduction
Estimated Value 46.3
Confidence Interval (2-Sided) 95%
36.2 to 54.8
Estimation Comments Derived as 100 x (1 - Geometric LS Mean Ratio)
Other Statistical Analysis Mixed model conducted on log-transformed values with visit, log-transformed baseline value and its interaction with visit, sex, Caucasian origin, product use pattern category and its interaction with visit, and other baseline covariates relevant for the specific clinical risk endpoint as fixed effect factors and site as a random effect
8.Primary Outcome
Title Levels of Carboxyhemoglobin (COHb).
Hide Description Carboxyhemoglobin (COHb) is assayed from whole blood. Expressed as % of saturation of hemoglobin. Geometric Mean values are provided as descriptive statistics.
Time Frame 52 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set - As Exposed Analysis (FAS-EX). Some participants were excluded from analysis for protocol deviations (including, but not limited to, missing measurements).
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use
Hide Arm/Group Description:

The "THS 2.2 use" product use category was defined as THS use of 70% or more over the entire analysis period.

(≥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.)

The "CC use" product use category was defined as THS use of less than 1% over the entire 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.)

The "Dual use" product use category was defined as THS use of less than 70% over the entire 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.)

"Other use" refers to any other product use over the entire analysis period. (Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns.)
Overall Number of Participants Analyzed 141 257 86 26
Geometric Mean (95% Confidence Interval)
Unit of Measure: percent change
2.59
(2.24 to 3.01)
4.06
(3.77 to 4.38)
3.92
(3.44 to 4.46)
5.22
(4.47 to 6.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection THS 2.2 Use, CC Use
Comments The analysis will determine the effect of THS 2.2 compared to CC at Month 12 on the components of the "smokers' health profile". This study has no formal pre-specified hypotheses associated with the study objectives. Estimates of THS 2.2 effect will be presented by mean of relative reduction of COHb levels between CC and THS 2.2 and related 95% CI.
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter % Relative Reduction
Estimated Value 31.7
Confidence Interval (2-Sided) 95%
23.3 to 39.1
Estimation Comments Derived as 100 x (1 - Geometric LS Mean Ratio)
Other Statistical Analysis Mixed model conducted on log-transformed values with visit, log-transformed baseline value and its interaction with visit, sex, Caucasian origin, product use pattern category and its interaction with visit, and other baseline covariates relevant for the specific clinical risk endpoint as fixed effect factors and site as a random effect.
Time Frame 18 months (from March 2015 to September 2016)
Adverse Event Reporting Description Of the 984 subjects who started the original study (NCT02396381), 20 subjects without a valid safety assessment and 24 subjects from a site terminated for non-GCP compliance were excluded from the safety population (N=940). The safety population comprised the 857 subjects of the Full Analysis Set - As Exposed (FAS-EX), who had at least one record of reported product use post randomization, and 83 subjects who were randomized and had at least 1 valid safety assessment.
 
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use
Hide Arm/Group Description

The "THS 2.2 use" product use category was defined as THS use of 70% or more over the entire analysis period.

(≥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.)

The "CC use" product use category was defined as THS use of less than 1% over the entire 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.)

The "Dual use" product use category was defined as THS use of less than 70% over the entire 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.)

.

"Other use" refers to any other product use over the entire analysis period. (Subjects with missing product use data, subjects using e-cigarettes or other tobacco products, quitters, or subjects who switched across different use patterns.)
All-Cause Mortality
THS 2.2 Use CC Use Dual Use Other Use
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/241 (0.41%)      1/434 (0.23%)      0/159 (0.00%)      1/106 (0.94%)    
Hide Serious Adverse Events
THS 2.2 Use CC Use Dual Use Other Use
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   12/241 (4.98%)      15/434 (3.46%)      1/159 (0.63%)      1/106 (0.94%)    
Cardiac disorders         
Acute myocardial infarction * 1  0/241 (0.00%)  0 1/434 (0.23%)  1 0/159 (0.00%)  0 0/106 (0.00%)  0
Gastrointestinal disorders         
Pancreatitis chronic * 1  0/241 (0.00%)  0 1/434 (0.23%)  1 0/159 (0.00%)  0 0/106 (0.00%)  0
General disorders         
Death * 1  0/241 (0.00%)  0 1/434 (0.23%)  1 0/159 (0.00%)  0 0/106 (0.00%)  0
Infections and infestations         
Appendicitis with Peritonitis * 1  1/241 (0.41%)  2 0/434 (0.00%)  0 0/159 (0.00%)  0 0/106 (0.00%)  0
Cellulitis * 1  0/241 (0.00%)  0 1/434 (0.23%)  1 0/159 (0.00%)  0 0/106 (0.00%)  0
Cellulitis staphylococcal * 1  0/241 (0.00%)  0 1/434 (0.23%)  1 0/159 (0.00%)  0 0/106 (0.00%)  0
Epiglottitis * 1  1/241 (0.41%)  1 0/434 (0.00%)  0 0/159 (0.00%)  0 0/106 (0.00%)  0
Influenza * 1  1/241 (0.41%)  1 0/434 (0.00%)  0 0/159 (0.00%)  0 0/106 (0.00%)  0
Pneumonia mycoplasmal * 1  1/241 (0.41%)  1 0/434 (0.00%)  0 0/159 (0.00%)  0 0/106 (0.00%)  0
Tooth infection * 1  0/241 (0.00%)  0 1/434 (0.23%)  1 0/159 (0.00%)  0 0/106 (0.00%)  0
Urosepsis with Nephrolithiasis * 1  0/241 (0.00%)  0 1/434 (0.23%)  2 0/159 (0.00%)  0 0/106 (0.00%)  0
Pyelonephritis Acute * 1  0/241 (0.00%)  0 1/434 (0.23%)  1 1/159 (0.63%)  1 0/106 (0.00%)  0
Injury, poisoning and procedural complications         
Head injury with Seizure * 1  1/241 (0.41%)  2 0/434 (0.00%)  0 0/159 (0.00%)  0 0/106 (0.00%)  0
Hip fracture * 1  1/241 (0.41%)  1 0/434 (0.00%)  0 0/159 (0.00%)  0 0/106 (0.00%)  0
Laceration * 1  1/241 (0.41%)  1 0/434 (0.00%)  0 0/159 (0.00%)  0 0/106 (0.00%)  0
Multiple fractures * 1  0/241 (0.00%)  0 0/434 (0.00%)  0 1/159 (0.63%)  1 0/106 (0.00%)  0
Rib fracture, Clavicle fracture, Pulmonary contusion, Pleural effusion, and Traumatic Hemothorax * 1  0/241 (0.00%)  0 1/434 (0.23%)  5 0/159 (0.00%)  0 0/106 (0.00%)  0
Foot Fracture * 1  1/241 (0.41%)  1 0/434 (0.00%)  0 0/159 (0.00%)  0 0/106 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Costochondritis * 1  1/241 (0.41%)  1 0/434 (0.00%)  0 0/159 (0.00%)  0 0/106 (0.00%)  0
Vertebral osteophyte with Cervical Myelopathy * 1  0/241 (0.00%)  0 1/434 (0.23%)  2 0/159 (0.00%)  0 0/106 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Breast cancer * 1  0/241 (0.00%)  0 1/434 (0.23%)  2 0/159 (0.00%)  0 0/106 (0.00%)  0
Metastases to small intestine with Anaemia * 1  0/241 (0.00%)  0 0/434 (0.00%)  0 0/159 (0.00%)  0 1/106 (0.94%)  2
Papillary thyroid cancer * 1  0/241 (0.00%)  0 1/434 (0.23%)  1 0/159 (0.00%)  0 0/106 (0.00%)  0
Nervous system disorders         
Transient ischaemic attack * 1  0/241 (0.00%)  0 1/434 (0.23%)  1 0/159 (0.00%)  0 0/106 (0.00%)  0
Psychiatric disorders         
Alchohol abuse * 1  0/241 (0.00%)  0 0/434 (0.00%)  0 0/159 (0.00%)  0 1/106 (0.94%)  1
Completed suicide * 1  1/241 (0.41%)  1 0/434 (0.00%)  0 0/159 (0.00%)  0 0/106 (0.00%)  0
Suicidal ideation * 1  0/241 (0.00%)  0 1/434 (0.23%)  1 0/159 (0.00%)  0 0/106 (0.00%)  0
Reproductive system and breast disorders         
Menorrhagia * 1  1/241 (0.41%)  1 0/434 (0.00%)  0 0/159 (0.00%)  0 0/106 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Pneumonia aspiration * 1  1/241 (0.41%)  1 0/434 (0.00%)  0 0/159 (0.00%)  0 0/106 (0.00%)  0
Social circumstances         
Bereavement and Adjustment Disorder with Depressed Mood * 1  0/241 (0.00%)  0 0/434 (0.00%)  0 0/159 (0.00%)  0 1/106 (0.94%)  2
Vascular disorders         
Peripheral ischaemia * 1  0/241 (0.00%)  0 1/434 (0.23%)  1 0/159 (0.00%)  0 0/106 (0.00%)  0
1
Term from vocabulary, MedDRA (18.0)
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
THS 2.2 Use CC Use Dual Use Other Use
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   40/241 (16.60%)      87/434 (20.05%)      26/159 (16.35%)      13/106 (12.26%)    
Infections and infestations         
Upper respiratory tract infection * 1  21/241 (8.71%)  25 40/434 (9.22%)  45 11/159 (6.92%)  14 8/106 (7.55%)  9
Investigations         
Blood triglycerides increased * 1  10/241 (4.15%)  10 26/434 (5.99%)  28 6/159 (3.77%)  6 1/106 (0.94%)  1
Vascular disorders         
Hypertension * 1  9/241 (3.73%)  13 26/434 (5.99%)  40 9/159 (5.66%)  11 4/106 (3.77%)  5
1
Term from vocabulary, MedDRA (18.0)
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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
Layout table for Results Point of Contact information
Name/Title: Christelle Haziza
Organization: Philip Morris Products S.A.
Phone: +41 58 242 11 11
EMail: christelle.haziza@pmi.com
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Responsible Party: Philip Morris Products S.A.
ClinicalTrials.gov Identifier: NCT02649556    
Other Study ID Numbers: ZRHR-ERS-09-EXT-US
ZRHR-ERS-09-EXT-US ( Other Identifier: Philip Morris Products S.A. )
First Submitted: January 5, 2016
First Posted: January 7, 2016
Results First Submitted: May 25, 2020
Results First Posted: December 4, 2020
Last Update Posted: December 4, 2020