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Reduced Exposure Study Using CHTP 1.0 During 5 Days in Confinement.

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: NCT02503254
Recruitment Status : Completed
First Posted : July 20, 2015
Results First Posted : March 10, 2017
Last Update Posted : January 30, 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: CHTP 1.0
Other: Conventional Cigarette (CC)
Enrollment 85
Recruitment Details

Study initiated (first subject screened): 04 July 2015

At admission (Day -3), all the subjects performed a product trial of the CHTP 1.0. During the baseline period, they continued smoking their single preferred brand of CC. Then, on Day -1, subjects were randomized to one of the two study arms (CHTP 1.0 or CC) in a 1:1 ratio.

Pre-assignment Details

Enrolled and randomized population = 80 subjects

  • 41 subjects in CHTP 1.0 arm
  • 39 subjects in CC arm

Number of subjects enrolled but NOT randomized (who tried the CHTP 1.0 at Day -3) = 5

Arm/Group Title CHTP 1.0 Conventional Cigarette (CC)
Hide Arm/Group Description Ad libitum use of the Carbon Heated Tobacco Product 1.0 (CHTP 1.0) for 5 days in confinement Ad libitum use of subject's own preferred brand of CC for 5 days in confinement
Period Title: Overall Study
Started 41 39
Completed 41 39
Not Completed 0 0
Arm/Group Title CHTP 1.0 Conventional Cigarette (CC) Total
Hide Arm/Group Description Ad libitum use of the Carbon Heated Tobacco Product 1.0 (CHTP 1.0) for 5 days in confinement Ad libitum use of subject's own preferred brand of CC for 5 days in confinement Total of all reporting groups
Overall Number of Baseline Participants 41 39 80
Hide Baseline Analysis Population Description
The study population consisted of all the randomized subjects who had at least 1 post randomization product use experience (CHTP 1.0 or CC), and at least 1 valid non-safety assessment. 80 randomized subjects: 41 in CHTP 1.0 and 39 in CC study arms. All the randomized subjects completed the study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 41 participants 39 participants 80 participants
34.1  (10.45) 32.7  (10.97) 33.5  (10.66)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 39 participants 80 participants
Female
21
  51.2%
20
  51.3%
41
  51.2%
Male
20
  48.8%
19
  48.7%
39
  48.8%
International Organization for Standardization (ISO) nicotine level  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 41 participants 39 participants 80 participants
≤ 0.6 mg
32
  78.0%
34
  87.2%
66
  82.5%
> 0.6 to ≤ 1 mg
9
  22.0%
5
  12.8%
14
  17.5%
1.Primary Outcome
Title Concentration of Monohydroxybutenyl Mercapturic Acid (MHBMA)
Hide Description

Concentrations measured on Day 5 in urine, adjusted for creatinine.

Geometric Least Squares (LS) means are provided as descriptive statistics.

Time Frame 5 days
Hide Outcome Measure Data
Hide Analysis Population Description

The analysis was performed on the full analysis set (FAS) population.

The FAS consisted of all the randomized subjects who had at least 1 post randomization product use experience (CHTP 1.0 or CC) and had at least 1 non-safety assessment.

Arm/Group Title CHTP 1.0 Conventional Cigarette (CC)
Hide Arm/Group Description:
Ad libitum use of the Carbon Heated Tobacco Product 1.0 (CHTP 1.0) for 5 days in confinement
Ad libitum use of subject's own preferred brand of CC for 5 days in confinement
Overall Number of Participants Analyzed 41 39
Least Squares Mean (95% Confidence Interval)
Unit of Measure: pg/mg creat
327.08
(282.39 to 378.84)
1903.61
(1637.48 to 2212.99)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CHTP 1.0, Conventional Cigarette (CC)
Comments

The hypothesis to be tested is that the geometric mean level on Day 5 of the biomarker of exposure for CHTP 1.0 is lower relative to CC.

Analysis of the BoExp was conducted on the natural log scale in order to test the following hypothesis (one sided test with 2.5% type I error probability):

  • Null hypothesis (H0): m1≥m2
  • Alternative hypothesis (H1): m1<m2 Where m1 and m2 are the geometric means of the BoExp levels on Day 5 for CHTP 1.0 and CC, respectively.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments The primary endpoints were tested using a multiple testing procedure to preserve the overall alpha level by simultaneously testing the endpoints using a closed procedure with each test performed at a two-sided alpha level of 5%.
Method ANCOVA
Comments ANCOVA model on MHBMA levels with product, sex, cigarette consumption, and baseline value as covariates.
Method of Estimation Estimation Parameter Geometric LS Mean Reduction
Estimated Value 82.82
Confidence Interval (2-Sided) 95%
78.79 to 86.09
Estimation Comments

Geometric LS Mean Reduction = 100 - (CHTP 1.0 : CC ratio)

Expressed as %

2.Primary Outcome
Title Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA)
Hide Description

Concentrations measured on Day 5 in urine, adjusted for creatinine.

Geometric Least Squares means are provided as descriptive statistics.

Time Frame 5 days
Hide Outcome Measure Data
Hide Analysis Population Description

The analysis was performed on the full analysis set (FAS) population.

The FAS consisted of all the randomized subjects who had at least 1 post randomization product use experience (CHTP 1.0 or CC) and had at least 1 non-safety assessment.

Arm/Group Title CHTP 1.0 Conventional Cigarette (CC)
Hide Arm/Group Description:
Ad libitum use of the Carbon Heated Tobacco Product 1.0 (CHTP 1.0) for 5 days in confinement
Ad libitum use of subject's own preferred brand of CC for 5 days in confinement
Overall Number of Participants Analyzed 41 39
Least Squares Mean (95% Confidence Interval)
Unit of Measure: ng/mg creat
464.27
(432.13 to 498.80)
1272.96
(1182.66 to 1370.15)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CHTP 1.0, Conventional Cigarette (CC)
Comments

The hypothesis to be tested is that the geometric mean level on Day 5 of the biomarker of exposure for CHTP 1.0 is lower relative to CC.

Analysis of the BoExp was conducted on the natural log scale in order to test the following hypothesis (one sided test with 2.5% type I error probability):

  • Null hypothesis (H0): m1≥m2
  • Alternative hypothesis (H1): m1<m2 Where m1 and m2 are the geometric means of the BoExp levels on Day 5 for CHTP 1.0 and CC, respectively
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments The primary endpoints were tested using a multiple testing procedure to preserve the overall alpha level by simultaneously testing the endpoints using a closed procedure with each test performed at a two-sided alpha level of 5%.
Method ANCOVA
Comments ANCOVA model on 3-HPMA levels with product, sex, cigarette consumption, and baseline value as covariates.
Method of Estimation Estimation Parameter Geometric LS Mean Reduction
Estimated Value 63.53
Confidence Interval (2-Sided) 95%
59.55 to 67.12
Estimation Comments

Geometric LS Mean Reduction = 100 - (CHTP 1.0 : CC ratio)

Expressed as %

3.Primary Outcome
Title Concentration of S-phenylmercapturic Acid (S-PMA)
Hide Description

Concentrations measured on Day 5 in urine, adjusted for creatinine.

Geometric Least Squares means are provided as descriptive statistics.

Time Frame 5 days
Hide Outcome Measure Data
Hide Analysis Population Description

The analysis was performed on the full analysis set (FAS) population.

The FAS consisted of all the randomized subjects who had at least 1 post randomization product use experience (CHTP 1.0 or CC) and had at least 1 non-safety assessment.

Arm/Group Title CHTP 1.0 Conventional Cigarette (CC)
Hide Arm/Group Description:
Ad libitum use of the Carbon Heated Tobacco Product 1.0 (CHTP 1.0) for 5 days in confinement
Ad libitum use of subject's own preferred brand of CC for 5 days in confinement
Overall Number of Participants Analyzed 41 39
Least Squares Mean (95% Confidence Interval)
Unit of Measure: pg/mg creat
352.39
(321.26 to 386.54)
2971.98
(2703.14 to 3267.55)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CHTP 1.0, Conventional Cigarette (CC)
Comments

The hypothesis to be tested is that the geometric mean level on Day 5 of the biomarker of exposure for CHTP 1.0 is lower relative to CC.

Analysis of the BoExp was conducted on the natural log scale in order to test the following hypothesis (one sided test with 2.5% type I error probability):

  • Null hypothesis (H0): m1≥m2
  • Alternative hypothesis (H1): m1<m2 Where m1 and m2 are the geometric means of the BoExp levels on Day 5 for CHTP 1.0 and CC, respectively.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments The primary endpoints were tested using a multiple testing procedure to preserve the overall alpha level by simultaneously testing the endpoints using a closed procedure with each test performed at a two-sided alpha level of 5%.
Method ANCOVA
Comments ANCOVA model on MHBMA levels with product, sex, cigarette consumption, and baseline value as covariates
Method of Estimation Estimation Parameter Geometric LS Mean Reduction
Estimated Value 88.14
Confidence Interval (2-Sided) 95%
86.46 to 89.62
Estimation Comments

Geometric LS Mean Reduction = 100 - (CHTP 1.0 : CC ratio)

Expressed as %

4.Primary Outcome
Title Levels of Carboxyhemoglobin (COHb)
Hide Description

% COHb blood measurements performed in the evening of Day 5, expressed as % of saturation of hemoglobin.

Geometric Least Squares means are provided as descriptive statistics.

Time Frame 5 days
Hide Outcome Measure Data
Hide Analysis Population Description

The analysis was performed on the full analysis set (FAS) population: all randomized subjects who had at least 1 post randomization product use experience (CHTP 1.0 or CC) and had at least 1 non-safety assessment.

However, due to sample issues such as clotting, COHb assessment results could not be generated for some of the subjects.

Arm/Group Title CHTP 1.0 Conventional Cigarette (CC)
Hide Arm/Group Description:
Ad libitum use of the Carbon Heated Tobacco Product 1.0 (CHTP 1.0) for 5 days in confinement
Ad libitum use of subject's own preferred brand of CC for 5 days in confinement
Overall Number of Participants Analyzed 32 26
Least Squares Mean (95% Confidence Interval)
Unit of Measure: percentage of saturation of hemoglobin
2.660
(2.316 to 3.054)
6.460
(5.531 to 7.544)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection CHTP 1.0, Conventional Cigarette (CC)
Comments

The hypothesis to be tested is that the geometric mean level on Day 5 of the biomarker of exposure for CHTP 1.0 is lower relative to CC.

Analysis of the BoExp was conducted on the natural log scale in order to test the following hypothesis (one sided test with 2.5% type I error probability):

  • Null hypothesis (H0): m1≥m2
  • Alternative hypothesis (H1): m1<m2 Where m1 and m2 are the geometric means of the BoExp levels on Day 5 for CHTP 1.0 and CC respectively.
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments The primary endpoints were tested using a multiple testing procedure to preserve the overall alpha level by simultaneously testing the endpoints using a closed procedure with each test performed at an alpha level of 2.5% one sided.
Method ANCOVA
Comments ANCOVA model on COHb levels with product, sex, cigarette consumption, and baseline value as covariates.
Method of Estimation Estimation Parameter Geometric LS Mean Ratio
Estimated Value 58.83
Confidence Interval (2-Sided) 95%
49.30 to 66.56
Estimation Comments

Geometric LS Mean Reduction = 100 - (CHTP 1.0 : CC ratio)

Expressed as %

Time Frame From the informed consent form signature until the end of the safety follow-up period, up to 58 days (including a screening period of up to 42 days, a 9-day confinement period followed by a 7-day safety follow-up period (7 days after discharge of the subject or early discontinuation)).
Adverse Event Reporting Description The safety was assessed in the safety population, consisting of 85 subjects: 80 randomized subjects (41 in CHTP 1.0 and 39 in CC) and 5 subjects exposed to CHTP 1.0 during the product trial on Day -3 but not randomized.
 
Arm/Group Title CHTP 1.0 Conventional Cigarette (CC) Enrolled But Not Randomized
Hide Arm/Group Description Ad libitum use of the Carbon Heated Tobacco Product 1.0 (CHTP 1.0) for 5 days in confinement Ad libitum use of subject's own preferred brand of CC for 5 days in confinement Subjects who tried the CHTP 1.0 at Admission (Day -3) but were not randomized
All-Cause Mortality
CHTP 1.0 Conventional Cigarette (CC) Enrolled But Not Randomized
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Hide Serious Adverse Events
CHTP 1.0 Conventional Cigarette (CC) Enrolled But Not Randomized
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/41 (0.00%)      0/39 (0.00%)      1/5 (20.00%)    
Injury, poisoning and procedural complications       
Concussion * 1 [1]  0/41 (0.00%)  0 0/39 (0.00%)  0 1/5 (20.00%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.0
[1]
Concussion was considered to be moderate in intensity and not related to the CHTP 1.0 or CC but to study procedures. This serious adverse event was considered to have resolved after 4 days. The subject had no ongoing medical conditions at Screening
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
CHTP 1.0 Conventional Cigarette (CC) Enrolled But Not Randomized
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   27/41 (65.85%)      14/39 (35.90%)      5/5 (100.00%)    
Blood and lymphatic system disorders       
Leukocytosis * 1  2/41 (4.88%)  2 0/39 (0.00%)  0 1/5 (20.00%)  1
Gastrointestinal disorders       
Nausea * 1  0/41 (0.00%)  0 1/39 (2.56%)  1 1/5 (20.00%)  1
Vomiting * 1  0/41 (0.00%)  0 0/39 (0.00%)  0 2/5 (40.00%)  2
General disorders       
Vessel puncture site haematoma * 1  0/41 (0.00%)  0 2/39 (5.13%)  2 0/5 (0.00%)  0
Hepatobiliary disorders       
Hyperbilirubinaemia * 1  0/41 (0.00%)  0 2/39 (5.13%)  2 1/5 (20.00%)  1
Injury, poisoning and procedural complications       
Head injury * 1  0/41 (0.00%)  0 0/39 (0.00%)  0 1/5 (20.00%)  1
Metabolism and nutrition disorders       
Hypertriglyceridaemia * 1  0/41 (0.00%)  0 2/39 (5.13%)  2 2/5 (40.00%)  2
Hyperkalaemia * 1  0/41 (0.00%)  0 1/39 (2.56%)  1 1/5 (20.00%)  1
Hyperglycaemia * 1  0/41 (0.00%)  0 0/39 (0.00%)  0 1/5 (20.00%)  1
Nervous system disorders       
Headache * 1  19/41 (46.34%)  21 9/39 (23.08%)  13 3/5 (60.00%)  3
Syncope * 1  2/41 (4.88%)  2 1/39 (2.56%)  1 1/5 (20.00%)  1
Psychiatric disorders       
Agitation * 1  0/41 (0.00%)  0 0/39 (0.00%)  0 1/5 (20.00%)  1
Renal and urinary disorders       
Leukocyturia * 1  1/41 (2.44%)  1 0/39 (0.00%)  0 1/5 (20.00%)  1
Respiratory, thoracic and mediastinal disorders       
Cough * 1  13/41 (31.71%)  17 0/39 (0.00%)  0 0/5 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 18.0
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 specifies that in no event will the study site be allowed to disclose to any third party (or publicly release) any information obtained through the study without the CRO's prior written consent which in turn cannot provide such consent without Sponsor's approval unless such publication is made to satisfy regulatory requirements.

The Intellectual Property rights and research results from the present study belongs to the Sponsor.

Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Cam Tuan Tran
Organization: Philip Morris Products S.A.
Phone: +41 (58) 242 2620
EMail: CamTuan.Tran@pmi.com
Layout table for additonal information
Responsible Party: Philip Morris Products S.A.
ClinicalTrials.gov Identifier: NCT02503254    
Other Study ID Numbers: P2R-REXC-06-EU
P2R-REXC-06-EU ( Other Identifier: Philip Morris Products S.A. )
First Submitted: July 17, 2015
First Posted: July 20, 2015
Results First Submitted: November 4, 2016
Results First Posted: March 10, 2017
Last Update Posted: January 30, 2023