Reduced Exposure Study Using THS 2.2 Menthol With 5 Days in a Confinement Setting Followed by 86 Days in an Ambulatory Setting

• Sponsor: Philip Morris Products S.A. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01989156
• Collaborator: (none)
• Enrollment: 160
• Locations: 2
• Arms: 3
• Duration (Months): 17
• Patients Per Site: 80
• Patients Per Site Per Month: 4.7

Study Details

Study Description

Brief Summary

Evaluate if the ad libitum use of the THS 2.2 Menthol (mTHS), a candidate Modified Risk Tobacco Product, for 5 days in confinement, and after 86 days in an ambulatory setting, by apparently adult healthy smokers results in a reduction in the levels of biomarkers of exposure (BoExp) to selected harmful and potentially harmful constituents (HPHCs).

Condition or Disease	Intervention/Treatment	Phase
Smoking	Other: THS 2.2 Menthol (mTHS 2.2); Other: Menthol Conventional Cigarette (mCC); Other: Smoking Abstinence (SA)	N/A

Detailed Description

The main goal of the study is to evaluate if the ad libitum use of the THS 2.2 Menthol (mTHS) for 5 days in confinement, and after 86 days in an ambulatory setting, by apparently adult healthy smokers results in a reduction in the levels of biomarkers of exposure (BoExp) to selected harmful and potentially harmful constituents (HPHCs) compared to smokers continuing smoking their own preferred brand of menthol conventional cigarette (mCC) and smoking abstinence (SA). Smokers who remained abstinent from SA were used as a benchmark to provide context to the exposure reduction.

Study Design

• Study Type: Interventional
• Actual Enrollment: 160 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Randomized, Controlled, Open-label, 3-arm Parallel Group, Multi-center Study to Demonstrate Reductions in Exposure to Selected Smoke Constituents in Apparently Healthy Smokers Switching to the Tobacco Heating System 2.2 Menthol (THS 2.2 Menthol) or Observing Smoking Abstinence, Compared to Continuing to Use Menthol Conventional Cigarettes, for 5 Days in Confinement and Prolonged by 86 Days in an Ambulatory Setting
• Study Start Date: Dec 1, 2013
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: THS 2.2 Menthol (mTHS 2.2) Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting	Other: THS 2.2 Menthol (mTHS 2.2); THS 2.2 Menthol ad libitum for 5 days in confinement prolonged by 86 days in an ambulatory setting
Active Comparator: Menthol Conventional Cigarette (mCC) Ad libitum use of subject's own preferred brand of mCC for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting	Other: Menthol Conventional Cigarette (mCC); Subject's own preferred brand of mCC ad libitum for 5 days in confinement prolonged by 86 days in an ambulatory setting
Sham Comparator: Smoking abstinence (SA) Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting	Other: Smoking Abstinence (SA); SA for 5 days in confinement prolonged by 86 days in an ambulatory setting

Outcome Measures

Primary Outcome Measures

1. Concentration of Monohydroxybutenylmercapturic Acid (MHBMA) [5 days]

   Concentrations measured in urine, adjusted for creatinine, at Day 5 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.

2. Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA) [5 days]

   Concentrations measured in urine, adjusted for creatinine, at Day 5 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.

3. Concentration of S-phenylmercapturic Acid (S-PMA) [5 days]

   Concentrations measured in urine, adjusted for creatinine, at Day 5 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.

4. Levels of Total 4-(Methylnitrosamino)-1-(3- Pyridyl)-1-butanol (Total NNAL) [90 days]

   Concentrations measured in urine, adjusted for creatinine, at Day 90 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.

5. Levels of Carboxyhemoglobin (COHb) [5 days]

   Carboxyhemoglobin (COHb) is assayed from whole blood. Expressed as % of saturation of hemoglobin. Blood measurements performed in the evening of Day 5, for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 22 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Smoking, apparently healthy subject as judged by the Investigator.

• Subject smokes at least 10 commercially available mCCs per day (no brand restrictions) for the last 4 weeks, based on self-reporting.

• Subject has smoked for at least the last 3 consecutive years.

• Subject does not plan to quit smoking within the next 6 months.

Exclusion Criteria:

• As per Investigator judgment, the subject cannot participate in the study for any reason (e.g., medical, psychiatric, and/or social reason).

• The subject has received medication within 14 days or within 5 half-lives of the medication (whichever is longer), which has an impact on CYP1A2 or CYP2A6 activity.

• For women: Subject is pregnant or is breast feeding.

• For women: Subject does not agree to use an acceptable method of effective contraception.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Covance Daytona Beach, 1900 Mason Ave., Suite 140	Daytona Beach	Florida	United States	32117
2	Covance Dallas, 1341 W. Mockingbird Ln., Ste 400E	Dallas	Texas	United States	75247

Sponsors and Collaborators

• Philip Morris Products S.A.

Investigators

• Principal Investigator: William Lewis, MD, Covance Dallas
• Principal Investigator: Frank Farmer, MD, Covance Daytona Beach
• Study Chair: Christelle Haziza, PhD, Philip Morris Products S.A.

Study Documents (Full-Text)

• Study Protocol - Apr 14, 2014
• Statistical Analysis Plan - May 29, 2015

More Information

Publications

None provided.

• Responsible Party: Philip Morris Products S.A.
• ClinicalTrials.gov Identifier: NCT01989156
• Other Study ID Numbers: ZRHM-REXA-08-US; ZRHM-REXA-08-US
• First Posted: Nov 20, 2013
• Last Update Posted: Mar 24, 2020
• Last Verified: Mar 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Philip Morris Products S.A.: Smoking; Candidate modified risk tobacco product; Menthol conventional cigarettes; Reduced exposure; HPHCs; Ambulatory
• Additional relevant MeSH terms: Menthol

Study Results

Participant Flow

Recruitment Details	Study initiated (first subject screened): 17 December 2013 At admission (Day -2), all the subjects performed a product trial of THS 2.2 Menthol. During the baseline period, they continued to smoke their single preferred brand of mCC. Then, on Day 0, they were randomized to one of the 3 study arms (mTHS 2.2, mCC or SA) in a 2:1:1 ratio.
Pre-assignment Detail	Enrolled and randomized population = 160 subjects 80 subjects in mTHS 2.2 41 subjects in mCC 39 subjects in SA Number of subjects exposed to the product test = 165 Number of subjects enrolled but NOT randomized = 4 Number of subjects failed screening = 1

Arm/Group Title	THS 2.2 Menthol (mTHS 2.2)	Menthol Conventional Cigarette (mCC)	Smoking Abstinence (SA)
Arm/Group Description	Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting	Ad libitum use of subject's own preferred brand of mCC for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting	Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting
Period Title: Confinement Period (Population at Day 5)
STARTED	80	41	39
COMPLETED	80	40	34
NOT COMPLETED	0	1	5
Period Title: Confinement Period (Population at Day 5)
STARTED	80	40	34
COMPLETED	73	35	31
NOT COMPLETED	7	5	3

Baseline Characteristics

Arm/Group Title	THS 2.2 Menthol (mTHS 2.2)	Menthol Conventional Cigarette (mCC)	Smoking Abstinence (SA)	Total
Arm/Group Description	Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting	Ad libitum use of subject's own preferred brand of mCC for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting	Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting	Total of all reporting groups
Overall Participants	80	41	39	160
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.2 (11.72)	33.7 (10.17)	38.8 (11.42)	37.7 (11.45)
Sex: Female, Male (Count of Participants)
Female	32 40%	17 41.5%	15 38.5%	64 40%
Male	48 60%	24 58.5%	24 61.5%	96 60%
Daily mCC consumption at screening (participants) [Number]
10 to 19 cig/day	43 53.8%	21 51.2%	18 46.2%	82 51.3%
> 19 cig/day	36 45%	20 48.8%	21 53.8%	77 48.1%

Outcome Measures

1. Primary Outcome

Title	Concentration of Monohydroxybutenylmercapturic Acid (MHBMA)
Description	Concentrations measured in urine, adjusted for creatinine, at Day 5 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Per Protocol set (PP) which included all randomized subjects who had no major protocol deviation impacting the evaluability during the confinement period.

Arm/Group Title	THS 2.2 Menthol (mTHS 2.2)	Menthol Conventional Cigarette (mCC)	Smoking Abstinence (SA)
Arm/Group Description	Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting	Ad libitum use of subject's own preferred brand of mCC for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting	Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting
Measure Participants	65	30	21
Geometric Mean (95% Confidence Interval) [pg/mg creat]	110.96	882.25	94.97

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	THS 2.2 Menthol (mTHS 2.2), Menthol Conventional Cigarette (mCC)
	Comments	The hypothesis to be tested is that the geometric mean level on Day 5 of the biomarker of exposure for mTHS 2.2 is lower relative to mCC. Analysis of the biomarkers of exposure (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 mTHS 2.2 and mCC respectively.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
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 an alpha level of 2.5% one sided.
	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 Ratio
	Estimated Value	12.58
	Confidence Interval	(2-Sided) 95%; 9.27 to 17.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric LS Mean Ratio mTHS 2.2:mCC

2. Primary Outcome

Title	Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA)
Description	Concentrations measured in urine, adjusted for creatinine, at Day 5 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Per Protocol set (PP) which included all randomized subjects who had no major protocol deviation impacting the evaluability during the confinement period.

Arm/Group Title	THS 2.2 Menthol (mTHS 2.2)	Menthol Conventional Cigarette (mCC)	Smoking Abstinence (SA)
Arm/Group Description	Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting	Ad libitum use of subject's own preferred brand of mCC for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting	Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting
Measure Participants	67	30	21
Geometric Mean (95% Confidence Interval) [ng/mg creat]	278.13	607.68	152.05

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	THS 2.2 Menthol (mTHS 2.2), Menthol Conventional Cigarette (mCC)
	Comments	The hypothesis to be tested is that the geometric mean level on Day 5 of the biomarker of exposure for mTHS 2.2 is lower relative to mCC. 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 mTHS 2.2 and mCC respectively.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
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 an alpha level of 2.5% one sided.
	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 Ratio
	Estimated Value	45.77
	Confidence Interval	(2-Sided) 95%; 39.22 to 53.41
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric LS mean ratio mTHS 2.2:mCC

3. Primary Outcome

Title	Concentration of S-phenylmercapturic Acid (S-PMA)
Description	Concentrations measured in urine, adjusted for creatinine, at Day 5 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Per Protocol set (PP) which included all randomized subjects who had no major protocol deviation impacting the evaluability during the confinement period.

Arm/Group Title	THS 2.2 Menthol (mTHS 2.2)	Menthol Conventional Cigarette (mCC)	Smoking Abstinence (SA)
Arm/Group Description	Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting	Ad libitum use of subject's own preferred brand of mCC for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting	Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting
Measure Participants	65	30	21
Geometric Mean (95% Confidence Interval) [pg/mg creat]	134.11	1065.91	131.05

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	THS 2.2 Menthol (mTHS 2.2), Menthol Conventional Cigarette (mCC)
	Comments	The hypothesis to be tested is that the geometric mean level on Day 5 of the biomarker of exposure for mTHS 2.2 is lower relative to mCC. 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 mTHS 2.2 and mCC respectively.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
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 an alpha level of 2.5% one sided.
	Method	ANCOVA
	Comments	ANCOVA model on S-PMA levels with product, sex, cigarette consumption, and baseline value as covariates.
Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	12.58
	Confidence Interval	(2-Sided) 95%; 9.54 to 16.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric LS mean ratio mTHS 2.2:mCC

4. Primary Outcome

Title	Levels of Total 4-(Methylnitrosamino)-1-(3- Pyridyl)-1-butanol (Total NNAL)
Description	Concentrations measured in urine, adjusted for creatinine, at Day 90 for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Per Protocol set (PP) which included all randomized subjects who had no major protocol deviation impacting the evaluability during the confinement period.

Arm/Group Title	THS 2.2 Menthol (mTHS 2.2)	Menthol Conventional Cigarette (mCC)	Smoking Abstinence (SA)
Arm/Group Description	Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting	Ad libitum use of subject's own preferred brand of mCC for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting	Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting
Measure Participants	43	29	9
Geometric Mean (95% Confidence Interval) [pg/mg creat]	41.05	155.45	54.03

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	THS 2.2 Menthol (mTHS 2.2), Menthol Conventional Cigarette (mCC)
	Comments	The hypothesis to be tested is that the geometric mean level on Day 90 of the biomarker of exposure for mTHS 2.2 is lower relative to mCC. 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 90 for mTHS 2.2 and mCC respectively.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
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 an alpha level of 2.5% one sided.
	Method	ANCOVA
	Comments	ANCOVA model on Total NNAL levels with product, sex, cigarette consumption, and baseline value as covariates
Method of Estimation	Estimation Parameter	Geometric LS Mean Ratio
	Estimated Value	26.41
	Confidence Interval	(2-Sided) 95%; 17.31 to 40.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric LS mean ratio mTHS 2.2:mCC

5. Primary Outcome

Title	Levels of Carboxyhemoglobin (COHb)
Description	Carboxyhemoglobin (COHb) is assayed from whole blood. Expressed as % of saturation of hemoglobin. Blood measurements performed in the evening of Day 5, for the smokers of all arms (mTHS, mCC and SA). Geometric Least Squares means are provided as descriptive statistics.
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

The analysis was performed on the Per Protocol set (PP) which included all randomized subjects who had no major protocol deviation impacting the evaluability during the confinement period.

Arm/Group Title	THS 2.2 Menthol (mTHS 2.2)	Menthol Conventional Cigarette (mCC)	Smoking Abstinence (SA)
Arm/Group Description	Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting	Ad libitum use of subject's own preferred brand of mCC for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting	Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting
Measure Participants	74	34	23
Geometric Mean (95% Confidence Interval) [% of saturation of hemoglobin]	2.33	6.11	2.39

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	THS 2.2 Menthol (mTHS 2.2), Menthol Conventional Cigarette (mCC)
	Comments	The hypothesis to be tested is that the geometric mean level on Day 90 of the biomarker of exposure for mTHS 2.2 is lower relative to mCC. 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 90 for mTHS 2.2 and mCC respectively.
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
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 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	38.14
	Confidence Interval	(2-Sided) 95%; 34.24 to 42.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	Geometric LS mean ratio mTHS 2.2:mCC

Adverse Events

Time Frame	From the informed consent form (ICF) signature until the end of the safety follow-up period, up to 150 days (including a screening period of up to 28 days, an 8-day confinement period followed by an 85-day ambulatory setting, and by a 28-day safety follow-up period (28 days after discharge of the subject or early discontinuation)).
Adverse Event Reporting Description	The adverse events and serious adverse events reported are for the post-randomization period. The safety was assessed in the safety population, consisting of 165 subjects: 160 randomized subjects (80 in mTHS 2.2, 41 in mCC and 39 in SA) and 5 subjects exposed to mTHS 2.2 from the product trial on Day -2 but not randomized. After randomization, the Safety Population consisted of 160 subjects with one valid post-randomization safety assessment.
Arm/Group Title	THS 2.2 Menthol (mTHS 2.2)		Menthol Conventional Cigarette (mCC)		Smoking Abstinence (SA)
Arm/Group Description	Ad libitum use of THS 2.2 Menthol for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting		Ad libitum use of subject's own preferred brand of mCC for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting		Abstinence from smoking for 5 Days in a Confinement Setting and 86 Days in an Ambulatory Setting
All Cause Mortality
	THS 2.2 Menthol (mTHS 2.2)		Menthol Conventional Cigarette (mCC)		Smoking Abstinence (SA)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	THS 2.2 Menthol (mTHS 2.2)		Menthol Conventional Cigarette (mCC)		Smoking Abstinence (SA)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/80 (0%)		0/41 (0%)		0/39 (0%)
Other (Not Including Serious) Adverse Events
	THS 2.2 Menthol (mTHS 2.2)		Menthol Conventional Cigarette (mCC)		Smoking Abstinence (SA)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/80 (38.8%)		12/41 (29.3%)		16/39 (41%)
Infections and infestations
Upper respiratory tract infection	3/80 (3.8%)	3	4/41 (9.8%)	4	1/39 (2.6%)	1
Injury, poisoning and procedural complications
Muscle strain	0/80 (0%)	0	0/41 (0%)	0	2/39 (5.1%)	2
Investigations
Blood triglycerides increased	2/80 (2.5%)	2	2/41 (4.9%)	3	2/39 (5.1%)	2
Haemoglobin decreased	11/80 (13.8%)	14	4/41 (9.8%)	5	6/39 (15.4%)	8
Lymphocyte count increased	6/80 (7.5%)	7	2/41 (4.9%)	2	1/39 (2.6%)	1
Neutrophil count decreased	4/80 (5%)	5	0/41 (0%)	0	0/39 (0%)	0
Nervous system disorders
Dizziness	1/80 (1.3%)	1	0/41 (0%)	0	2/39 (5.1%)	2
Headache	4/80 (5%)	4	1/41 (2.4%)	1	3/39 (7.7%)	4

Limitations/Caveats

Analysis of Primary Outcomes required data from the PP set at Baseline, Day 5 (MHBMA, 3-HPMA, S-PMA, and COHb), and Day 90 (Total NNAL). Differences in the number of participants for each outcome is due to missing data at baseline or at Day5/90.

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 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 belong to the Sponsor.