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Evaluation of Biological and Functional Changes in Healthy Smokers After Switching to THS 2.2 for 26 Weeks

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: NCT02396381
Recruitment Status : Completed
First Posted : March 24, 2015
Results First Posted : August 21, 2019
Last Update Posted : January 26, 2023
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 1039
Recruitment Details  
Pre-assignment Details

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
Hide 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 [1] 488 496
Full Analysis Set - As Exposed (FAS-EX) [2] 414 443
Completed 381 422
Not Completed 107 74
Reason Not Completed
Adverse Event             3             2
Withdrawal by Subject             33             24
Lost to Follow-up             49             31
Protocol Violation             1             0
Site terminated by sponsor             7             8
Physician Decision             5             5
Pregnancy             2             0
Non-compliance with study procedures             1             0
Moved out of town/state             1             3
Could not complete visit             1             0
Possible conflict of interest             1             0
Randomization/Screening Error             3             1
[1]
Randomized
[2]
Subjects with at least one record of reported use post-randomization.
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use Total
Hide 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 Number of Baseline Participants 245 428 142 42 857
Hide Baseline Analysis Population Description
Full Analysis Set - As Exposed (FAS-EX)
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 245 participants 428 participants 142 participants 42 participants 857 participants
44.2  (9.64) 45.2  (9.55) 43.8  (9.77) 44.2  (8.14) 44.6  (9.55)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 245 participants 428 participants 142 participants 42 participants 857 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)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 245 participants 428 participants 142 participants 42 participants 857 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
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 245 participants 428 participants 142 participants 42 participants 857 participants
American Indian or Alaska Native
2
   0.8%
2
   0.5%
2
   1.4%
0
   0.0%
6
   0.7%
Asian
2
   0.8%
5
   1.2%
0
   0.0%
1
   2.4%
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
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
   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  
Mean (Standard Deviation)
Unit of measure:  Kg/m2
Number Analyzed 245 participants 428 participants 142 participants 42 participants 857 participants
26.9  (3.99) 27.1  (4.13) 26.9  (4.35) 26.9  (5.12) 27.0  (4.18)
1.Primary Outcome
Title Levels of High Density Lipoprotein C (HDL-C).
Hide Description

Concentrations measured in serum.

Geometric Least Squares means are provided as descriptive statistics.
Time Frame 26 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set - As Exposed (FAS-EX)
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use
Hide 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.
Overall Number of Participants Analyzed 245 428 142 42
Geometric Mean (95% Confidence Interval)
Unit of Measure: mg/dL
54.1
(51.4 to 56.7)
50.9
(49.4 to 52.4)
56.3
(52.7 to 59.9)
52.8
(47.4 to 58.1)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
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
Estimation Comments [Not Specified]
2.Primary Outcome
Title Levels of White Blood Cells (WBC).
Hide Description

Concentrations measured in blood.

Geometric Least Squares means are provided as descriptive statistics.
Time Frame 26 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set - As Exposed (FAS-EX)
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use
Hide 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.
Overall Number of Participants Analyzed 245 428 142 42
Geometric Mean (95% Confidence Interval)
Unit of Measure: GI/L
6.98
(6.70 to 7.25)
7.48
(7.28 to 7.69)
7.41
(7.00 to 7.82)
8.71
(7.80 to 9.62)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
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
Estimation Comments [Not Specified]
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).

Geometric Least Squares means are provided as descriptive statistics.
Time Frame 26 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set - As Exposed (FAS-EX)
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use
Hide 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.
Overall Number of Participants Analyzed 245 428 142 42
Geometric Mean (95% Confidence Interval)
Unit of Measure: Percent of predicted FEV1
95.4
(93.7 to 97.1)
93.4
(92.0 to 94.8)
93.7
(91.3 to 96.0)
94.3
(89.3 to 99.4)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
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
Estimation Comments [Not Specified]
4.Primary Outcome
Title Concentrations of Soluble Intercellular Adhesion Molecule 1 (sICAM-1).
Hide Description

Concentrations measured in serum.

Geometric Least Squares means are provided as descriptive statistics.
Time Frame 26 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set - As Exposed (FAS-EX)
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use
Hide 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.
Overall Number of Participants Analyzed 245 428 142 42
Geometric Mean (95% Confidence Interval)
Unit of Measure: ng/mL
252
(239 to 266)
266
(253 to 279)
270
(253 to 288)
273
(234 to 317)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.030
Comments [Not Specified]
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
Estimation Comments Derived as 1 - LS Mean Ratio (THS / CC)
5.Primary Outcome
Title Concentrations of 11-dehydrothromboxane B2 (11-DTXB2).
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set - As Exposed (FAS-EX)
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use
Hide 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.
Overall Number of Participants Analyzed 245 428 142 42
Geometric Mean (95% Confidence Interval)
Unit of Measure: pg/mg creat
496
(446 to 551)
523
(482 to 568)
532
(464 to 610)
626
(504 to 777)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.193
Comments [Not Specified]
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
Estimation Comments Derived as 1 - LS Mean Ratio (THS / CC)
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.

Geometric Least Squares means are provided as descriptive statistics.
Time Frame 26 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set - As Exposed (FAS-EX)
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use
Hide 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.
Overall Number of Participants Analyzed 245 428 142 42
Geometric Mean (95% Confidence Interval)
Unit of Measure: pg/mg creat
321
(299 to 344)
351
(334 to 369)
347
(318 to 377)
335
(281 to 400)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments [Not Specified]
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
Estimation Comments Derived as 1 - LS Mean Ratio (THS / CC)
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.

Geometric Least Squares means are provided as descriptive statistics.
Time Frame 26 Weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set - As Exposed (FAS-EX)
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use
Hide 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.
Overall Number of Participants Analyzed 245 428 142 42
Geometric Mean (95% Confidence Interval)
Unit of Measure: pg/mg creat
144
(118 to 175)
282
(254 to 314)
286
(244 to 334)
342
(254 to 460)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
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
Estimation Comments Derived as 1 - LS Mean Ratio (THS / CC)
8.Primary Outcome
Title Percent Change From Baseline of Carboxyhemoglobin (COHb)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set - As Exposed (FAS-EX)
Arm/Group Title THS 2.2 Use CC Use Dual Use Other Use
Hide 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.
Overall Number of Participants Analyzed 245 428 142 42
Geometric Mean (95% Confidence Interval)
Unit of Measure: percentage change from baseline
2.84
(2.51 to 3.20)
4.38
(4.16 to 4.61)
4.23
(3.80 to 4.70)
5.59
(4.87 to 6.41)
Hide 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 [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
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
Estimation Comments Derived as 1 - LS Mean Ratio (THS / CC)
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.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title THS 2.2 Group CC Group Product Test
Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/477 (0.42%)      0/483 (0.00%)      0/52 (0.00%)    
Hide 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 (1.26%)      7/483 (1.45%)      0/52 (0.00%)    
Infections and infestations       
Pneumonia mycoplasmal * 1  1/477 (0.21%)  1 0/483 (0.00%)  0 0/52 (0.00%)  0
Cellulitis * 1  0/477 (0.00%)  0 1/483 (0.21%)  1 0/52 (0.00%)  0
Pyelonephritis acute, with Urosepsis and Nephrolithiasis * 1  0/477 (0.00%)  0 1/483 (0.21%)  3 0/52 (0.00%)  0
Tooth Infection * 1  0/477 (0.00%)  0 1/483 (0.21%)  1 0/52 (0.00%)  0
Injury, poisoning and procedural complications       
Head injury with seizure * 1  1/477 (0.21%)  2 0/483 (0.00%)  0 0/52 (0.00%)  0
Laceration * 1  1/477 (0.21%)  1 0/483 (0.00%)  0 0/52 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Vertebral osteophyte with Cervical myelopathy * 1  0/477 (0.00%)  0 1/483 (0.21%)  2 0/52 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Papillary thyroid cancer * 1  0/477 (0.00%)  0 1/483 (0.21%)  1 0/52 (0.00%)  0
Metastases to small intestine with anaemia * 1  1/477 (0.21%)  2 0/483 (0.00%)  0 0/52 (0.00%)  0
Psychiatric disorders       
Completed suicide * 1  1/477 (0.21%)  1 0/483 (0.00%)  0 0/52 (0.00%)  0
Suicidal ideation * 1  0/477 (0.00%)  0 1/483 (0.21%)  1 0/52 (0.00%)  0
Alcohol abuse * 1  1/477 (0.21%)  1 0/483 (0.00%)  0 0/52 (0.00%)  0
Adjustment disorder with depressed mood and bereavement * 1  0/477 (0.00%)  0 1/483 (0.21%)  2 0/52 (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 Group CC Group Product Test
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   23/477 (4.82%)      29/483 (6.00%)      0/52 (0.00%)    
Infections and infestations       
Upper respiratory tract infection * 1  23/477 (4.82%)  26 29/483 (6.00%)  33 0/52 (0.00%)  0
1
Term from vocabulary, MedDRA (18.0)
*
Indicates events were collected by non-systematic assessment
[Not Specified]
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: ClinicalTrials.PMI@pmi.com
Publications of Results:
Ludicke F, Ansari SM, Lama N, Blanc N, Bosilkovska M, Donelli A, Picavet P, Baker G, Haziza C, Peitsch M, Weitkunat R. Effects of Switching to a Heat-Not-Burn Tobacco Product on Biologically Relevant Biomarkers to Assess a Candidate Modified Risk Tobacco Product: A Randomized Trial. Cancer Epidemiol Biomarkers Prev. 2019 Nov;28(11):1934-1943. doi: 10.1158/1055-9965.EPI-18-0915. Epub 2019 Jul 3.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Philip Morris Products S.A.
ClinicalTrials.gov Identifier: NCT02396381    
Other Study ID Numbers: ZRHR-ERS-09-US
ZRHR-ERS-09-US ( Other Identifier: Philip Morris Products S.A. )
First Submitted: March 18, 2015
First Posted: March 24, 2015
Results First Submitted: July 27, 2018
Results First Posted: August 21, 2019
Last Update Posted: January 26, 2023