Reduced Exposure Study Using the CHTP 1.2 With 5 Days in a Confinement Setting Followed by 85 Days in an Ambulatory Setting.

• ClinicalTrials.gov Identifier: NCT02641587
• Recruitment Status: Completed
• First Posted: December 29, 2015
• Results First Posted: March 6, 2019
• Last Update Posted: March 27, 2020
• Sponsor: Philip Morris Products S.A.
• 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 1.2; Other: CC
• Enrollment: 121

Participant Flow

Recruitment Details
Pre-assignment Details	Following enrollment of 121 subjects, each subject received a product test of CHTP 1.2 prior to randomization. One subject was not randomized due to the physician's decision. This subject is included in the "Exposed Not Randomized" reporting group of the Baseline Characteristics. Consequently, 120 subjects were randomized.

Arm/Group Title	CHTP 1.2	Cigarettes (CC)
Arm/Group Description	Ad libitum use of the CHTP 1.2 CHTP 1.2: Ad libitum use of the CHTP 1.2 for 5 days in confinement followed by 85 days in an ambulatory setting.	Ad libitum use of subject's own preferred non-menthol brand of CC CC: Ad libitum use of subject's own preferred non-menthol brand of CC for 5 days in confinement followed by 85 days in an ambulatory setting.
Period Title: Confinement Period
Started	80	40
Completed	77	39
Not Completed	3	1
Reason Not Completed
Adverse Event	1	0
Withdrawal by Subject	2	1
Period Title: Ambulatory Period
Started	77	39
Completed	76	39
Not Completed	1	0
Reason Not Completed
Withdrawal by Subject	1	0

Baseline Characteristics

Arm/Group Title		CHTP 1.2	Cigarettes (CC)	Exposed Not Randomized	Total
Arm/Group Description		Ad libitum use of the CHTP 1.2 CHTP 1.2: Ad libitum use of the CHTP 1.2 for 5 days in confinement followed by 85 days in an ambulatory setting.	Ad libitum use of subject's own preferred non-menthol brand of CC CC: Ad libitum use of subject's own preferred non-menthol brand of CC for 5 days in confinement followed by 85 days in an ambulatory setting.	"Exposed not randomized" refers to all subjects exposed to CHTP 1.2 but not randomized.	Total of all reporting groups
Overall Number of Baseline Participants		80	40	1	121
Baseline Analysis Population Description		Overall safety population refers to all subjects who were exposed and randomized or exposed and not randomized.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	80 participants	40 participants	1 participants	121 participants
		38.9 (8.9)	39.0 (8.0)	28	38.8 (8.6)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	80 participants	40 participants	1 participants	121 participants
	Female	36 45.0%	20 50.0%	1 100.0%	57 47.1%
	Male	44 55.0%	20 50.0%	0 0.0%	64 52.9%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	80 participants	40 participants	1 participants	121 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	White	80 100.0%	40 100.0%	0 0.0%	120 99.2%
	More than one race	0 0.0%	0 0.0%	1 100.0%	1 0.8%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%
BMI; Mean (Standard Deviation); Unit of measure: Kg/m2
	Number Analyzed	80 participants	40 participants	1 participants	121 participants
		25.74 (3.51)	25.70 (2.96)	21.7	25.69 (3.33)

Outcome Measures

1. Primary Outcome

Title	Concentrations of Monohydroxybutenylmercapturic Acid (MHBMA)
Description	Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric least squares (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors.
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population

Arm/Group Title	CHTP 1.2	Cigarettes (CC)
Arm/Group Description:	Ad libitum use of the CHTP 1.2 CHTP 1.2: Ad libitum use of the CHTP 1.2 for 5 days in confinement followed by 85 days in an ambulatory setting.	Ad libitum use of subject's own preferred non-menthol brand of CC CC: Ad libitum use of subject's own preferred non-menthol brand of CC for 5 days in confinement followed by 85 days in an ambulatory setting.
Overall Number of Participants Analyzed	74	34
Geometric Least Squares Mean (95% Confidence Interval); Unit of Measure: pg/mg creat
	285.5; (258.0 to 315.8)	1904; (1641 to 2209)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CHTP 1.2, Cigarettes (CC)
	Comments	Analysis will be conducted on the natural log scale. The Day 5 levels of MHBMA will be analyzed by means of a generalized linear model using randomized arm as covariate adjusting for sex, average cigarette consumption over the previous 6 weeks prior to Admission (value at Admission for stratification), and log-transformed baseline value of MHBMA.
	Type of Statistical Test	Other
	Comments	The analysis will test if the geometric LS mean level of MHBMA for CHTP is lower than for CC. The following hypothesis will be evaluated: H0: XCHTP - XCC ≤ 0.0 HA: XCHTP - XCC > 0.0 where XCHTP and XCC are the geometric LS means of CHTP and CC, respectively. H0 is rejected with a type I error α = 2.5% (one-sided test).
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The primary endpoints will be 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	Generalized linear model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Reduction
	Estimated Value	85.01
	Confidence Interval	(2-Sided) 95%; 82.06 to 87.47
	Estimation Comments	Least squares (LS) means and estimate of the difference, and 95% CI will be back-transformed for obtaining geometric LS means for each arm, the reduction (calculated as 100% - ratio of CHTP 1.2 : CC [%]), and their 95% CI.

2. Primary Outcome

Title	Concentration of 3-hydroxypropylmercapturic Acid (3-HPMA)
Description	Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric least squares (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors.
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population

Arm/Group Title	CHTP 1.2	Cigarettes (CC)
Arm/Group Description:	Ad libitum use of the CHTP 1.2 CHTP 1.2: Ad libitum use of the CHTP 1.2 for 5 days in confinement followed by 85 days in an ambulatory setting.	Ad libitum use of subject's own preferred non-menthol brand of CC CC: Ad libitum use of subject's own preferred non-menthol brand of CC for 5 days in confinement followed by 85 days in an ambulatory setting.
Overall Number of Participants Analyzed	74	34
Geometric Least Squares Mean (95% Confidence Interval); Unit of Measure: ng/mg creat
	616.8; (565.6 to 672.8)	1031; (907.9 to 1172)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CHTP 1.2, Cigarettes (CC)
	Comments	Analysis will be conducted on the natural log scale. The Day 5 levels of 3-HPMA will be analyzed by means of a generalized linear model using randomized arm as covariate adjusting for sex, average cigarette consumption over the previous 6 weeks prior to Admission (value at Admission for stratification), and log-transformed baseline value of 3-HPMA.
	Type of Statistical Test	Other
	Comments	The analysis will test if the geometric LS mean level of 3-HPMA for CHTP is lower than for CC. The following hypothesis will be evaluated: H0: XCHTP - XCC ≤ 0.0 HA: XCHTP - XCC > 0.0 where XCHTP and XCC are the geometric LS means of CHTP and CC, respectively. H0 is rejected with a type I error α = 2.5% (one-sided test).
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The primary endpoints will be 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	Generalized linear model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Reduction
	Estimated Value	40.20
	Confidence Interval	(2-Sided) 95%; 30.25 to 48.73
	Estimation Comments	Least squares (LS) means and estimate of the difference, and 95% CI will be back-transformed for obtaining geometric LS means for each arm, the reduction (calculated as 100% - ratio of CHTP 1.2 : CC [%]), and their 95% CI.

3. Primary Outcome

Title	Concentration of S-phenylmercapturic Acid (S-PMA)
Description	Concentrations measured at Day 5 in urine, adjusted for creatinine. Geometric least squares (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors.
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population

Arm/Group Title	CHTP 1.2	Cigarettes (CC)
Arm/Group Description:	Ad libitum use of the CHTP 1.2 CHTP 1.2: Ad libitum use of the CHTP 1.2 for 5 days in confinement followed by 85 days in an ambulatory setting.	Ad libitum use of subject's own preferred non-menthol brand of CC CC: Ad libitum use of subject's own preferred non-menthol brand of CC for 5 days in confinement followed by 85 days in an ambulatory setting.
Overall Number of Participants Analyzed	74	34
Geometric Least Squares Mean (95% Confidence Interval); Unit of Measure: pg/mg creat
	386.6; (358.7 to 416.7)	2401; (2151 to 2681)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CHTP 1.2, Cigarettes (CC)
	Comments	Analysis will be conducted on the natural log scale. The Day 5 levels of S-PMA will be analyzed by means of a generalized linear model using randomized arm as covariate adjusting for sex, average cigarette consumption over the previous 6 weeks prior to Admission (value at Admission for stratification), and log-transformed baseline value of S-PMA.
	Type of Statistical Test	Other
	Comments	The analysis will test if the geometric LS mean level of S-PMA for CHTP is lower than for CC. The following hypothesis will be evaluated: H0: XCHTP - XCC ≤ 0.0 HA: XCHTP - XCC > 0.0 where XCHTP and XCC are the geometric LS means of CHTP and CC, respectively. H0 is rejected with a type I error α = 2.5% (one-sided test).
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The primary endpoints will be 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	Generalized linear model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Reduction
	Estimated Value	83.90
	Confidence Interval	(2-Sided) 95%; 81.61 to 85.90
	Estimation Comments	Least squares (LS) means and estimate of the difference, and 95% CI will be back-transformed for obtaining geometric LS means for each arm, the reduction (calculated as 100% - ratio of CHTP 1.2 : CC [%]), and their 95% CI.

4. Primary Outcome

Title	Levels of Carboxyhemoglobin (COHb)
Description	% COHb blood measurements performed in the evening of Day 5, expressed as % of saturation of hemoglobin. Geometric least squares (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 5 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors.
Time Frame	5 days

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population

Arm/Group Title	CHTP 1.2	Cigarettes (CC)
Arm/Group Description:	Ad libitum use of the CHTP 1.2 CHTP 1.2: Ad libitum use of the CHTP 1.2 for 5 days in confinement followed by 85 days in an ambulatory setting.	Ad libitum use of subject's own preferred non-menthol brand of CC CC: Ad libitum use of subject's own preferred non-menthol brand of CC for 5 days in confinement followed by 85 days in an ambulatory setting.
Overall Number of Participants Analyzed	58	22
Geometric Least Squares Mean (95% Confidence Interval); Unit of Measure: % of saturation of hemoglobin
	2.01; (1.86 to 2.16)	4.53; (4.01 to 5.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CHTP 1.2, Cigarettes (CC)
	Comments	Analysis will be conducted on the natural log scale. The Day 5 levels of COHb will be analyzed by means of a generalized linear model using randomized arm as covariate adjusting for sex, average cigarette consumption over the previous 6 weeks prior to Admission (value at Admission for stratification), and log-transformed baseline value of COHb.
	Type of Statistical Test	Other
	Comments	The analysis will test if the geometric LS mean level of COHb for CHTP is lower than for CC. The following hypothesis will be evaluated: H0: XCHTP - XCC ≤ 0.0 HA: XCHTP - XCC > 0.0 where XCHTP and XCC are the geometric LS means of CHTP and CC, respectively. H0 is rejected with a type I error α = 2.5% (one-sided test).
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The primary endpoints will be 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	Generalized linear model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Reduction
	Estimated Value	55.74
	Confidence Interval	(2-Sided) 95%; 49.03 to 61.56
	Estimation Comments	Least squares (LS) means and estimate of the difference, and 95% CI will be back-transformed for obtaining geometric LS means for each arm, the reduction (calculated as 100% - ratio of CHTP 1.2 : CC [%]), and their 95% CI.

5. Primary Outcome

Title	Concentrations of Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL)
Description	Concentrations measured at Day 90 in urine, adjusted for creatinine. Geometric least squares (LS) means and confidence intervals (Cls) from a generalized linear model conducted on log-transformed Day 90 values with log-transformed baseline value, study arm, sex and CC consumption reported at admission as fixed effect factors.
Time Frame	90 days

Outcome Measure Data

Analysis Population Description

Per Protocol (PP) population

Arm/Group Title	CHTP 1.2	Cigarettes (CC)
Arm/Group Description:	Ad libitum use of the CHTP 1.2 CHTP 1.2: Ad libitum use of the CHTP 1.2 for 5 days in confinement followed by 85 days in an ambulatory setting.	Ad libitum use of subject's own preferred non-menthol brand of CC CC: Ad libitum use of subject's own preferred non-menthol brand of CC for 5 days in confinement followed by 85 days in an ambulatory setting.
Overall Number of Participants Analyzed	57	35
Geometric Least Squares Mean (95% Confidence Interval); Unit of Measure: pg/mg creat
	37.26; (31.39 to 44.24)	180.6; (144.8 to 225.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CHTP 1.2, Cigarettes (CC)
	Comments	Analysis will be conducted on the natural log scale. The Day 5 levels of Total NNAL will be analyzed by means of a generalized linear model using randomized arm as covariate adjusting for sex, average cigarette consumption over the previous 6 weeks prior to Admission (value at Admission for stratification), and log-transformed baseline value of Total NNAL.
	Type of Statistical Test	Other
	Comments	The analysis will test if the geometric LS mean level of Total NNAL for CHTP is lower than for CC. The following hypothesis will be evaluated: H0: XCHTP - XCC ≤ 0.0 HA: XCHTP - XCC > 0.0 where XCHTP and XCC are the geometric LS means of CHTP and CC, respectively. H0 is rejected with a type I error α = 2.5% (one-sided test).
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	The primary endpoints will be 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	Generalized linear model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	LS Mean Reduction
	Estimated Value	79.36
	Confidence Interval	(2-Sided) 95%; 72.73 to 84.39
	Estimation Comments	Least squares (LS) means and estimate of the difference, and 95% CI will be back-transformed for obtaining geometric LS means for each arm, the reduction (calculated as 100% - ratio of CHTP 1.2 : CC [%]), and their 95% CI.

Adverse Events

Time Frame

Adverse events were collected from the signature of the Informed Consent Form (ICF) until the end of the safety follow-up period, which covered a period of between 128 to 169 days for each subject.

Adverse Event Reporting Description

[Not Specified]

Arm/Group Title

Product Test

CHTP 1.2 Confinement

CC Confinement

CHTP 1.2 Ambulatory

CC Ambulatory

CHTP 1.2 Safety FU

CC Safety FU

CHTP 1.2 Post-Randomization

CC Post-Randomization

Arm/Group Description

After all inclusion/exclusion criteria were checked, all eligible subjects were enrolled and performed a product test using up to five CHTP 1.2

Ad libitum use of the CHTP 1.2 for 5 days in confinement.

Ad libitum use of subject's own preferred non-menthol brand of CC for 5 days in confinement.

Ad libitum use of the CHTP 1.2 for 85 days in an ambulatory setting.

Ad libitum use of subject's own preferred non-menthol brand of CC for 85 days in an ambulatory setting.

CHTP 1.2 Safety Follow-Up period of 28 days

CC Safety Follow-Up period of 28 days

CHTP 1.2 Post-Randomization period

CC Post-Randomization period

All-Cause Mortality

Product Test

CHTP 1.2 Confinement

CC Confinement

CHTP 1.2 Ambulatory

CC Ambulatory

CHTP 1.2 Safety FU

CC Safety FU

CHTP 1.2 Post-Randomization

CC Post-Randomization

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Affected / at Risk (%)

Total

0/121 (0.00%)

0/80 (0.00%)

0/40 (0.00%)

0/77 (0.00%)

0/39 (0.00%)

0/80 (0.00%)

0/40 (0.00%)

0/80 (0.00%)

0/40 (0.00%)

Serious Adverse Events

Product Test

CHTP 1.2 Confinement

CC Confinement

CHTP 1.2 Ambulatory

CC Ambulatory

CHTP 1.2 Safety FU

CC Safety FU

CHTP 1.2 Post-Randomization

CC Post-Randomization

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Total

0/121 (0.00%)

1/80 (1.25%)

0/40 (0.00%)

1/77 (1.30%)

1/39 (2.56%)

0/80 (0.00%)

0/40 (0.00%)

2/80 (2.50%)

1/40 (2.50%)

Infections and infestations

Appendicitis 1

0/121 (0.00%)

0

0/80 (0.00%)

0

0/40 (0.00%)

0

1/77 (1.30%)

1

0/39 (0.00%)

0

0/80 (0.00%)

0

0/40 (0.00%)

0

1/80 (1.25%)

1

0/40 (0.00%)

0

Peritonsillar Abscess 1

0/121 (0.00%)

0

1/80 (1.25%)

1

0/40 (0.00%)

0

0/77 (0.00%)

0

0/39 (0.00%)

0

0/80 (0.00%)

0

0/40 (0.00%)

0

1/80 (1.25%)

1

0/40 (0.00%)

0

Injury, poisoning and procedural complications

Joint Dislocation 1

0/121 (0.00%)

0

0/80 (0.00%)

0

0/40 (0.00%)

0

0/77 (0.00%)

0

1/39 (2.56%)

1

0/80 (0.00%)

0

0/40 (0.00%)

0

0/80 (0.00%)

0

1/40 (2.50%)

1

1 Term from vocabulary, MedDRA version 18.0

Other (Not Including Serious) Adverse Events

Frequency Threshold for Reporting Other Adverse Events

5%

Product Test

CHTP 1.2 Confinement

CC Confinement

CHTP 1.2 Ambulatory

CC Ambulatory

CHTP 1.2 Safety FU

CC Safety FU

CHTP 1.2 Post-Randomization

CC Post-Randomization

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Affected / at Risk (%)

# Events

Total

62/121 (51.24%)

37/80 (46.25%)

12/40 (30.00%)

50/77 (64.94%)

26/39 (66.67%)

1/80 (1.25%)

1/40 (2.50%)

64/80 (80.00%)

31/40 (77.50%)

Gastrointestinal disorders

1

2/121 (1.65%)

2

9/80 (11.25%)

9

2/40 (5.00%)

2

6/77 (7.79%)

6

2/39 (5.13%)

2

0/80 (0.00%)

0

1/40 (2.50%)

3

12/80 (15.00%)

15

5/40 (12.50%)

7

General disorders

Vessel Puncture Site Bruise 1

6/121 (4.96%)

6

5/80 (6.25%)

5

1/40 (2.50%)

1

0/77 (0.00%)

0

0/39 (0.00%)

0

0/80 (0.00%)

0

0/40 (0.00%)

0

5/80 (6.25%)

5

1/40 (2.50%)

1

General disorders † 1

6/121 (4.96%)

6

6/80 (7.50%)

6

3/40 (7.50%)

3

1/77 (1.30%)

1

1/39 (2.56%)

1

0/80 (0.00%)

0

0/40 (0.00%)

0

7/80 (8.75%)

7

4/40 (10.00%)

4

Infections and infestations

Nasopharyngitis 1

3/121 (2.48%)

3

6/80 (7.50%)

6

2/40 (5.00%)

2

9/77 (11.69%)

9

1/39 (2.56%)

1

0/80 (0.00%)

0

0/40 (0.00%)

0

14/80 (17.50%)

15

3/40 (7.50%)

3

Injury, poisoning and procedural complications

1

0/121 (0.00%)

0

0/80 (0.00%)

0

0/40 (0.00%)

0

0/77 (0.00%)

0

2/39 (5.13%)

2

1/80 (1.25%)

1

0/40 (0.00%)

0

1/80 (1.25%)

1

2/40 (5.00%)

2

Investigations

Alanine Aminotransferase Increased 1

1/121 (0.83%)

1

3/80 (3.75%)

3

0/40 (0.00%)

0

3/77 (3.90%)

3

1/39 (2.56%)

1

0/80 (0.00%)

0

0/40 (0.00%)

0

6/80 (7.50%)

6

1/40 (2.50%)

1

Blood Triglycerides Increased 1

1/121 (0.83%)

1

0/80 (0.00%)

0

0/40 (0.00%)

0

1/77 (1.30%)

1

2/39 (5.13%)

2

0/80 (0.00%)

0

0/40 (0.00%)

0

1/80 (1.25%)

1

2/40 (5.00%)

2

Metabolism and nutrition disorders

Hyperglycaemia 1

4/121 (3.31%)

4

2/80 (2.50%)

2

0/40 (0.00%)

0

14/77 (18.18%)

15

4/39 (10.26%)

4

0/80 (0.00%)

0

0/40 (0.00%)

0

15/80 (18.75%)

17

4/40 (10.00%)

4

Hypertriglyceridaemia 1

8/121 (6.61%)

8

0/80 (0.00%)

0

0/40 (0.00%)

0

3/77 (3.90%)

3

1/39 (2.56%)

1

0/80 (0.00%)

0

0/40 (0.00%)

0

3/80 (3.75%)

3

1/40 (2.50%)

1

Musculoskeletal and connective tissue disorders

1

1/121 (0.83%)

1

4/80 (5.00%)

4

0/40 (0.00%)

0

1/77 (1.30%)

1

0/39 (0.00%)

0

0/80 (0.00%)

0

0/40 (0.00%)

0

5/80 (6.25%)

5

0/40 (0.00%)

0

Nervous system disorders

Headache 1

42/121 (34.71%)

54

9/80 (11.25%)

10

4/40 (10.00%)

7

14/77 (18.18%)

15

8/39 (20.51%)

9

0/80 (0.00%)

0

0/40 (0.00%)

0

20/80 (25.00%)

25

11/40 (27.50%)

16

Respiratory, thoracic and mediastinal disorders

Oropharyngeal Pain 1

1/121 (0.83%)

1

2/80 (2.50%)

2

2/40 (5.00%)

2

3/77 (3.90%)

3

2/39 (5.13%)

2

0/80 (0.00%)

0

0/40 (0.00%)

0

5/80 (6.25%)

5

4/40 (10.00%)

4

Cough 1

0/121 (0.00%)

0

4/80 (5.00%)

4

0/40 (0.00%)

0

2/77 (2.60%)

2

2/39 (5.13%)

2

0/80 (0.00%)

0

1/40 (2.50%)

1

6/80 (7.50%)

6

3/40 (7.50%)

3

Skin and subcutaneous tissue disorders

Rash 1

0/121 (0.00%)

0

5/80 (6.25%)

5

0/40 (0.00%)

0

1/77 (1.30%)

1

0/39 (0.00%)

0

0/80 (0.00%)

0

0/40 (0.00%)

0

6/80 (7.50%)

6

0/40 (0.00%)

0

1 Term from vocabulary, MedDRA version 18.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

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

• Name/Title: Christelle Haziza
• Organization: Philip Morris Products S.A.
• Phone: +41 58 242 11 11
• EMail: christelle.haziza@pmi.com

• Responsible Party: Philip Morris Products S.A.
• ClinicalTrials.gov Identifier: NCT02641587
• Other Study ID Numbers: P2R-REXA-07-EU
• First Submitted: December 23, 2015
• First Posted: December 29, 2015
• Results First Submitted: October 2, 2018
• Results First Posted: March 6, 2019
• Last Update Posted: March 27, 2020