Trial Outcomes & Findings for A Smoking Cessation Study to Understand the Biological and Functional Changes After One Year of Smoking Cessation (NCT NCT02432729)

NCT ID: NCT02432729

Last Updated: 2023-01-30

Results Overview

Concentrations of HDL-C measured in serum. Mean values are provided as descriptive statistics.

• Recruitment status: COMPLETED
• Target enrollment: 1184 participants
• Primary outcome timeframe: Baseline; 6 month; 12 month
• Results posted on: 2023-01-30

Participant Flow

Participant milestones

Measure	Abstinence3m Set Enrolled subjects, who were abstinent from smoking from their actual quit date to at least Month 3, were included in the Abstinence3m set.
Month 3 Visit STARTED	720
Month 3 Visit COMPLETED	718
Month 3 Visit NOT COMPLETED	2
Month 6 Visit STARTED	718
Month 6 Visit COMPLETED	632
Month 6 Visit NOT COMPLETED	86
Month 12 Visit STARTED	632
Month 12 Visit COMPLETED	436
Month 12 Visit NOT COMPLETED	196

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Smoking Cessation Study to Understand the Biological and Functional Changes After One Year of Smoking Cessation

Baseline characteristics by cohort

Measure	Enrolled n=1184 Participants The Enrolled population included all subjects in the Full Safety Population, except 22 subjects enrolled at a site that was closed due to findings during a monitoring visit.
Age, Continuous	44.1 years STANDARD_DEVIATION 8.87 • n=5 Participants
Sex: Female, Male Female	591 Participants n=5 Participants
Sex: Female, Male Male	593 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants
Race (NIH/OMB) Asian	344 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	88 Participants n=5 Participants
Race (NIH/OMB) White	744 Participants n=5 Participants
Race (NIH/OMB) More than one race	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Hispanic or Latino	73 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Not Hispanic or Latino	776 Participants n=5 Participants
Race/Ethnicity, Customized Ethnicity · Japanese	335 Participants n=5 Participants
Weight	73.4 kg STANDARD_DEVIATION 14.9 • n=5 Participants
Height	170 cm STANDARD_DEVIATION 9.15 • n=5 Participants
BMI	25.4 kg/m^2 STANDARD_DEVIATION 4.02 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Concentrations of HDL-C measured in serum. Mean values are provided as descriptive statistics.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
High Density Lipoprotein C (HDL-C). Baseline	57.1 mg/dL Interval 55.8 to 58.4
High Density Lipoprotein C (HDL-C). Month 6	58.9 mg/dL Interval 57.1 to 60.7
High Density Lipoprotein C (HDL-C). Month 12	58.6 mg/dL Interval 56.6 to 60.5

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Concentrations of LDL-C measured in serum. Mean values are provided as descriptive statistics.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
Low-density Lipoprotein Cholesterol (LDL-C) Baseline	131 mg/dL Interval 128.0 to 134.0
Low-density Lipoprotein Cholesterol (LDL-C) Month 6	136 mg/dL Interval 132.0 to 140.0
Low-density Lipoprotein Cholesterol (LDL-C) Month 12	138 mg/dL Interval 134.0 to 142.0

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Concentrations of Apolipoprotein A1 measured in serum. Mean values are provided as descriptive statistics.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
Apo A1 Baseline	155 mg/dL Interval 153.0 to 158.0
Apo A1 Month 6	158 mg/dL Interval 155.0 to 161.0
Apo A1 Month 12	155 mg/dL Interval 152.0 to 158.0

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Concentrations of Apolipoprotein B measured in serum. Mean values are provided as descriptive statistics.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
Apo B Month 12	97.5 mg/dL Interval 94.8 to 100.0
Apo B Baseline	94.3 mg/dL Interval 92.4 to 96.2
Apo B Month 6	96.3 mg/dL Interval 93.8 to 98.7

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Concentrations of WBC measured in blood. Mean values are provided as descriptive statistics.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
White Blood Cells (WBC). Baseline	6.72 GI/L Interval 6.58 to 6.86
White Blood Cells (WBC). Month 6	5.94 GI/L Interval 5.79 to 6.09
White Blood Cells (WBC). Month 12	5.93 GI/L Interval 5.75 to 6.11

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Concentrations of high sensitivity C-reactive protein (hs-CRP) measured in serum. Geometric mean values are provided as descriptive statistics.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
Hs-CRP Baseline (mg/L)	0.856 mg/L Interval 0.776 to 0.944
Hs-CRP Month 6 (mg/L)	0.841 mg/L Interval 0.752 to 0.941
Hs-CRP Month 12 (mg/L)	0.963 mg/L Interval 0.846 to 1.1

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Concentrations of Homocysteine measured in plasma. Geometric mean values are provided as descriptive statistics.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
Homocysteine Baseline (μmol/L)	12.6 μmol/L Interval 12.3 to 12.9
Homocysteine Month 6 (μmol/L)	11.4 μmol/L Interval 11.1 to 11.8
Homocysteine Month 12 (μmol/L)	11.7 μmol/L Interval 11.3 to 12.0

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Concentrations of Fibrinogen measured in plasma. Geometric mean values are provided as descriptive statistics.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
Fibrinogen Baseline (mg/dL)	326 mg/dL Interval 321.0 to 331.0
Fibrinogen Month 6 (mg/dL)	310 mg/dL Interval 304.0 to 316.0
Fibrinogen Month 12 (mg/dL)	312 mg/dL Interval 305.0 to 319.0

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Concentrations of Platelets measured in plasma. Geometric mean values are provided as descriptive statistics.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
Platelets Baseline (GI/L)	239 GI/L Interval 235.0 to 243.0
Platelets Month 6 (GI/L)	240 GI/L Interval 235.0 to 245.0
Platelets Month 12 (GI/L)	241 GI/L Interval 236.0 to 246.0

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Concentrations measured in urine and expressed as concentration adjusted for creatinine. Geometric mean values are provided as descriptive statistics.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
11-dehydrothromboxane B2 (11-DTXB2). Baseline (pg/mg creat)	572 pg/mg creat Interval 546.0 to 601.0
11-dehydrothromboxane B2 (11-DTXB2). Month 6 (pg/mg creat)	433 pg/mg creat Interval 409.0 to 458.0
11-dehydrothromboxane B2 (11-DTXB2). Month 12 (pg/mg creat)	436 pg/mg creat Interval 411.0 to 463.0

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Concentrations of 8-epi-PGF2α measured in urine and expressed as concentration adjusted for creatinine. Geometric Means are provided as descriptive statistics.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
8-epi-prostaglandin F2α (8-epi-PGF2α). Baseline (pg/mg creat)	242 pg/mg creat Interval 233.0 to 251.0
8-epi-prostaglandin F2α (8-epi-PGF2α). Month 6 (pg/mg creat)	199 pg/mg creat Interval 190.0 to 207.0
8-epi-prostaglandin F2α (8-epi-PGF2α). Month 12 (pg/mg creat)	189 pg/mg creat Interval 180.0 to 197.0

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Concentrations of Myeloperoxidase measured in serum. Geometric mean values are provided as descriptive statistics.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
MPO Baseline (μg/L)	133 μg/L Interval 126.0 to 140.0
MPO Month 6 (μg/L)	144 μg/L Interval 133.0 to 155.0
MPO Month 12 (μg/L)	202 μg/L Interval 187.0 to 217.0

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Concentrations of sICAM-1 measured in serum. Geometric mean values are provided as descriptive statistics.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
Soluble Intercellular Adhesion Molecule 1 (sICAM-1). Baseline (ng/mL)	229 ng/mL Interval 223.0 to 236.0
Soluble Intercellular Adhesion Molecule 1 (sICAM-1). Month 6 (ng/mL)	201 ng/mL Interval 195.0 to 207.0
Soluble Intercellular Adhesion Molecule 1 (sICAM-1). Month 12 (ng/mL)	194 ng/mL Interval 187.0 to 200.0

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Concentrations of Albumin measured in urine and expressed as concentration adjusted for creatinine. Geometric mean values are provided as descriptive statistics.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
Albumin Baseline (mg/g creat)	5.68 mg/g creat Interval 5.36 to 6.03
Albumin Month 6 (mg/g creat)	5.69 mg/g creat Interval 5.28 to 6.13
Albumin Month 12 (mg/g creat)	5.51 mg/g creat Interval 5.12 to 5.94

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Carboxyhemoglobin (COHb) is assayed from whole blood. Expressed as % of saturation of hemoglobin. Geometric means are provided as descriptive statistics.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
Carboxyhemoglobin (COHb). Baseline	2.78 percentage Interval 2.61 to 2.96
Carboxyhemoglobin (COHb). Month 6	0.724 percentage Interval 0.664 to 0.789
Carboxyhemoglobin (COHb). Month 12	0.758 percentage Interval 0.691 to 0.831

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Glycosylated hemoglobin (HbA1c) is assayed from whole blood. Geometric means are provided as descriptive statistics.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
HbA1c Baseline	5.42 percentage of glycated hemoglobin Interval 5.39 to 5.44
HbA1c Month 6	5.39 percentage of glycated hemoglobin Interval 5.36 to 5.42
HbA1c Month 12	5.45 percentage of glycated hemoglobin Interval 5.42 to 5.49

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

FEV1 pre-bronchodilator and expressed as percentage predicted (FEV1 %pred).

Mean values are provided as descriptive statistics.

Spirometry is a physiological test that measures how an individual inhales or exhales volumes of air as a function of time. The primary signal measured in spirometry may be volume or flow. The forced expiratory volume (FEV) in one second is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
Forced Expiratory Volume in 1 Second (FEV1), Pre-bronchodilator and Expressed as Percentage Predicted (FEV1 %Pred). Baseline	94.5 Percent of predicted FEV1 Interval 93.7 to 95.4
Forced Expiratory Volume in 1 Second (FEV1), Pre-bronchodilator and Expressed as Percentage Predicted (FEV1 %Pred). Month 6	94.2 Percent of predicted FEV1 Interval 93.1 to 95.4
Forced Expiratory Volume in 1 Second (FEV1), Pre-bronchodilator and Expressed as Percentage Predicted (FEV1 %Pred). Month 12	93.9 Percent of predicted FEV1 Interval 92.6 to 95.3

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

FEV1 post-bronchodilator and expressed as percentage predicted (FEV1 %pred). Mean values are provided as descriptive statistics.

Spirometry is a physiological test that measures how an individual inhales or exhales volumes of air as a function of time. The primary signal measured in spirometry may be volume or flow. The forced expiratory volume (FEV) in one second is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
FEV1 Post-bronchodilator and Expressed as Percentage Predicted (FEV1 %Pred). Baseline	97.1 Percent of predicted FEV1 Interval 96.2 to 98.0
FEV1 Post-bronchodilator and Expressed as Percentage Predicted (FEV1 %Pred). Month 6	96.7 Percent of predicted FEV1 Interval 95.6 to 97.9
FEV1 Post-bronchodilator and Expressed as Percentage Predicted (FEV1 %Pred). Month 12	96.5 Percent of predicted FEV1 Interval 95.2 to 97.8

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Pre-bronchodilator Forced Vital Capacity, expressed as percentage predicted (FVC %pred). Mean values are provided as descriptive statistics.

Spirometry is a physiological test that measures how an individual inhales or exhales volumes of air as a function of time. The primary signal measured in spirometry may be volume or flow. The forced vital capacity (FVC) is the maximal volume of air exhaled with maximally forced effort from a maximal inspiration.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
Forced Vital Capacity (FVC) Pre-bronchodilator, Expressed as Percentage Predicted (FVC %Pred). Baseline	101 Percent of predicted FVC Interval 99.7 to 101.0
Forced Vital Capacity (FVC) Pre-bronchodilator, Expressed as Percentage Predicted (FVC %Pred). Month 6	100 Percent of predicted FVC Interval 99.0 to 101.0
Forced Vital Capacity (FVC) Pre-bronchodilator, Expressed as Percentage Predicted (FVC %Pred). Month 12	99.1 Percent of predicted FVC Interval 97.8 to 100.0

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Post-bronchodilator Forced Vital Capacity, expressed as percentage predicted (FVC %pred). Mean values are provided as descriptive statistics.

Spirometry is a physiological test that measures how an individual inhales or exhales volumes of air as a function of time. The primary signal measured in spirometry may be volume or flow. The forced vital capacity (FVC) is the maximal volume of air exhaled with maximally forced effort from a maximal inspiration.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
FVC Post-bronchodilator, Expressed as Percentage Predicted (FVC %Pred). Baseline	100 Percent of predicted FVC Interval 99.1 to 101.0
FVC Post-bronchodilator, Expressed as Percentage Predicted (FVC %Pred). Month 6	99.5 Percent of predicted FVC Interval 98.3 to 101.0
FVC Post-bronchodilator, Expressed as Percentage Predicted (FVC %Pred). Month 12	98.6 Percent of predicted FVC Interval 97.3 to 99.9

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Pre-bronchodilator FEV1/FVC expressed as a ratio. Mean values are provided as descriptive statistics.

Spirometry is a physiological test that measures how an individual inhales or exhales volumes of air as a function of time. The primary signal measured in spirometry may be volume or flow. The forced vital capacity (FVC) is the maximal volume of air exhaled with maximally forced effort from a maximal inspiration, and the forced expiratory volume (FEV) in one second is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
FEV1/FVC Pre-bronchodilator Expressed as a Ratio Baseline	0.771 ratio Interval 0.766 to 0.776
FEV1/FVC Pre-bronchodilator Expressed as a Ratio Month 6	0.77 ratio Interval 0.764 to 0.776
FEV1/FVC Pre-bronchodilator Expressed as a Ratio Month 12	0.778 ratio Interval 0.772 to 0.785

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Post-bronchodilator FEV1/FVC expressed as a ratio. Mean values are provided as descriptive statistics.

Spirometry is a physiological test that measures how an individual inhales or exhales volumes of air as a function of time. The primary signal measured in spirometry may be volume or flow. The forced vital capacity (FVC) is the maximal volume of air exhaled with maximally forced effort from a maximal inspiration, and the forced expiratory volume (FEV) in one second is the maximal volume of air exhaled in the first second of a forced expiration from a position of full inspiration.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
FEV1/FVC Post-bronchodilator Expressed as a Ratio Baseline	0.796 ratio Interval 0.791 to 0.8
FEV1/FVC Post-bronchodilator Expressed as a Ratio Month 6	0.797 ratio Interval 0.791 to 0.802
FEV1/FVC Post-bronchodilator Expressed as a Ratio Month 12	0.803 ratio Interval 0.797 to 0.809

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Pre-bronchodilator FEF 25-75, expressed as percentage predicted (FEF 25-75 %pred). Mean values are provided as descriptive statistics.

Spirometry is a physiological test that measures how an individual inhales or exhales volumes of air as a function of time. The forced expiratory flow between 25% and 75% of the FVC (FEF25-75%) is defined as the forced expiratory flow during the middle half of the FVC; the average flow from the point at which 25% of the FVC has been exhaled to the point at which 75% of the FVC has been exhaled.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
FEF 25-75 Forced Expiratory Flow, Pre-bronchodilator, Expressed as Percentage Predicted (FEF 25-75 %Pred) Baseline	84.8 Percent of predicted FEF 25-75% Interval 82.9 to 86.7
FEF 25-75 Forced Expiratory Flow, Pre-bronchodilator, Expressed as Percentage Predicted (FEF 25-75 %Pred) Month 6	84.2 Percent of predicted FEF 25-75% Interval 81.8 to 86.6
FEF 25-75 Forced Expiratory Flow, Pre-bronchodilator, Expressed as Percentage Predicted (FEF 25-75 %Pred) Month 12	86.6 Percent of predicted FEF 25-75% Interval 84.0 to 89.3

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Post-bronchodilator FEF 25-75, expressed as percentage predicted (FEF 25-75 %pred). Mean values are provided as descriptive statistics.

Spirometry is a physiological test that measures how an individual inhales or exhales volumes of air as a function of time. The forced expiratory flow between 25% and 75% of the FVC (FEF25-75%) is defined as the forced expiratory flow during the middle half of the FVC; the average flow from the point at which 25% of the FVC has been exhaled to the point at which 75% of the FVC has been exhaled.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
FEF 25-75 Forced Expiratory Flow, Post-bronchodilator, Expressed as Percentage Predicted (FEF 25-75 %Pred) Baseline	95.7 Percent of predicted FEF 25-75% Interval 93.7 to 97.7
FEF 25-75 Forced Expiratory Flow, Post-bronchodilator, Expressed as Percentage Predicted (FEF 25-75 %Pred) Month 6	95.8 Percent of predicted FEF 25-75% Interval 93.9 to 98.3
FEF 25-75 Forced Expiratory Flow, Post-bronchodilator, Expressed as Percentage Predicted (FEF 25-75 %Pred) Month 12	98.1 Percent of predicted FEF 25-75% Interval 95.4 to 101.0

PRIMARY outcome

Timeframe: Baseline; 6 month; 12 month

Population: Some subjects were prematurely discontinued from the study. Non-compliance with smoking abstinence was the most frequently reported reason for premature discontinuation from the study.

Concentrations of Total NNAL measured in urine and expressed as concentration adjusted for creatinine. Geometric means are provided as descriptive statistics.

Outcome measures

Measure	Abstinence3m n=720 Participants The Abstinence3m Set refers to enrolled subjects who were abstinent from smoking from their actual quit date to Month 3 (V8) or later.
Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL). Baseline (pg/mg creat)	125 pg/mg creat Interval 114.0 to 136.0
Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL). Month 6 (pg/mg creat)	5.11 pg/mg creat Interval 4.68 to 5.58
Total 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (Total NNAL). Month 12 (pg/mg creat)	4.37 pg/mg creat Interval 3.99 to 4.78

Adverse Events

Enrolled Population

Serious events: 17 serious events

Other events: 313 other events

Deaths: 1 deaths

Serious adverse events

Measure	Enrolled Population n=1184 participants at risk The Enrolled Population included 1184 subjects enrolled from the screened population.
Infections and infestations Pyelonephritis	0.17% 2/1184 • Number of events 5 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.
Infections and infestations Pneumonia	0.17% 2/1184 • Number of events 2 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.
Infections and infestations Urosepsis	0.08% 1/1184 • Number of events 4 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.
Infections and infestations Clostridium difficile colitis	0.08% 1/1184 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.
Infections and infestations Helicobacter gastritis	0.08% 1/1184 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.
Injury, poisoning and procedural complications Ankle fracture	0.08% 1/1184 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.
Injury, poisoning and procedural complications Cartilage injury	0.08% 1/1184 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.
Injury, poisoning and procedural complications Head injury	0.08% 1/1184 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.
Injury, poisoning and procedural complications Radius fracture	0.08% 1/1184 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.
Injury, poisoning and procedural complications Tendon rupture	0.08% 1/1184 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.08% 1/1184 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.08% 1/1184 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Osteoma	0.08% 1/1184 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.
Nervous system disorders Presyncope	0.08% 1/1184 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.
Nervous system disorders Ruptured cerebral aneurysm	0.08% 1/1184 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.
Cardiac disorders Atrial fibrilation	0.08% 1/1184 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.
Endocrine disorders Goitre	0.08% 1/1184 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.
Renal and urinary disorders Nephrolithiasis	0.08% 1/1184 • Number of events 1 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.

Other adverse events

Measure	Enrolled Population n=1184 participants at risk The Enrolled Population included 1184 subjects enrolled from the screened population.
Infections and infestations Nasopharyngitis	13.3% 158/1184 • Number of events 213 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.
Infections and infestations Upper respiratory tract infection	7.0% 83/1184 • Number of events 94 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.
Investigations Weight increased	6.1% 72/1184 • Number of events 74 • Adverse events were collected from the signature of the ICF by each subject until the end of the safety follow-up period, for a duration of up to 66 weeks for each subject.

Additional Information

Christelle Haziza, Director Health Science and Biostatistics

Philip Morris Products S.A.

Phone: +41 58 242 11 11

Email: christelle.haziza@pmi.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER