Trial Outcomes & Findings for Very-Low Nicotine Cigarettes and Non-Daily Smokers (NCT NCT02228824)

NCT ID: NCT02228824

Last Updated: 2018-10-31

Results Overview

Difference in mean daily cigarette consumption between initial two-week baseline period and final two weeks of experimental period, using imputed data

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 312 participants
• Primary outcome timeframe: Two-week pre-intervention baseline period compared to final two weeks of 10-week intervention period
• Results posted on: 2018-10-31

Participant Flow

Participants were recruited from the greater Pittsburgh area from June 2015 through April 2017 via various channels (e.g., advertisements on local television stations, public transportation, and social media such as Facebook and Instagram), as well as through University-housed research registries and recruiting services.

Participants may have been excluded from the study after enrollment but before assignment to an arm if they were found to be unable to adhere to the study protocol or were unable to attend study visits, opted to no longer participate, or if they became unable to contact (i.e., were lost to follow-up).

Participant milestones

Measure	Very Low Nicotine Content Cigarettes Very low nicotine content cigarettes: 0.07 mg nicotine delivery	Normal Nicotine Content Cigarettes Normal nicotine content cigarettes: 0.8 mg nicotine delivery
Overall Study STARTED	118	120
Overall Study COMPLETED	89	98
Overall Study NOT COMPLETED	29	22

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Very-Low Nicotine Cigarettes and Non-Daily Smokers

Baseline characteristics by cohort

Measure	Very Low Nicotine Content Cigarettes n=118 Participants Very low nicotine content cigarettes: 0.07 mg nicotine delivery	Normal Nicotine Content Cigarettes n=120 Participants Normal nicotine content cigarettes: 0.8 mg nicotine delivery	Total n=238 Participants Total of all reporting groups
Age, Continuous	37.4 years STANDARD_DEVIATION 13.5 • n=5 Participants	38.4 years STANDARD_DEVIATION 14.2 • n=7 Participants	37.9 years STANDARD_DEVIATION 13.8 • n=5 Participants
Sex: Female, Male Female	59 Participants n=5 Participants	71 Participants n=7 Participants	130 Participants n=5 Participants
Sex: Female, Male Male	59 Participants n=5 Participants	49 Participants n=7 Participants	108 Participants n=5 Participants
Race/Ethnicity, Customized Race · White	76 Participants n=5 Participants	76 Participants n=7 Participants	152 Participants n=5 Participants
Race/Ethnicity, Customized Race · Black	27 Participants n=5 Participants	34 Participants n=7 Participants	61 Participants n=5 Participants
Race/Ethnicity, Customized Race · Other	15 Participants n=5 Participants	10 Participants n=7 Participants	25 Participants n=5 Participants
Region of Enrollment United States	118 participants n=5 Participants	120 participants n=7 Participants	238 participants n=5 Participants
Cigarettes per day at enrollment (across all days)	1.9 cigarettes per day STANDARD_DEVIATION 1.6 • n=5 Participants	1.9 cigarettes per day STANDARD_DEVIATION 1.7 • n=7 Participants	1.9 cigarettes per day STANDARD_DEVIATION 1.7 • n=5 Participants
Smoking days per week at enrollment	3.7 smoking days per week STANDARD_DEVIATION 1.4 • n=5 Participants	3.7 smoking days per week STANDARD_DEVIATION 1.4 • n=7 Participants	3.7 smoking days per week STANDARD_DEVIATION 1.4 • n=5 Participants
Cigarettes per day at enrollment (smoking days only)	3.3 cigarettes per day STANDARD_DEVIATION 2.3 • n=5 Participants	3.5 cigarettes per day STANDARD_DEVIATION 2.9 • n=7 Participants	3.4 cigarettes per day STANDARD_DEVIATION 2.6 • n=5 Participants
Previous history of daily smoking	57 Participants n=5 Participants	61 Participants n=7 Participants	118 Participants n=5 Participants

PRIMARY outcome

Timeframe: Two-week pre-intervention baseline period compared to final two weeks of 10-week intervention period

Population: All participants who were randomized to an experimental condition (either very-low-nicotine-content cigarettes or normal-nicotine-content cigarettes)

Difference in mean daily cigarette consumption between initial two-week baseline period and final two weeks of experimental period, using imputed data

Outcome measures

Measure	Very Low Nicotine Content Cigarettes n=118 Participants Very low nicotine content cigarettes: 0.07 mg nicotine delivery	Normal Nicotine Content Cigarettes n=120 Participants Normal nicotine content cigarettes: 0.8 mg nicotine delivery
Change in Cigarette Consumption	-1.6 cigarettes per day Interval -2.0 to -1.1	-0.05 cigarettes per day Interval -0.5 to 0.4

SECONDARY outcome

Timeframe: Post-randomization time points at study weeks 4, 8, 12

The concentration of solanesol, a stable marker indicator of how much smoke has passed through the filter of a smoked cigarette to the smoker, will be assayed as a measure of smoking intensity. The filter of a cigarette butts smoked during the baseline period will be compared to those smoked during the experimental period.

Outcome measures

Measure	Very Low Nicotine Content Cigarettes n=118 Participants Very low nicotine content cigarettes: 0.07 mg nicotine delivery	Normal Nicotine Content Cigarettes n=120 Participants Normal nicotine content cigarettes: 0.8 mg nicotine delivery
Exposure Measure - Solanesol	NA mg/butt Standard Error NA Data for this measure will not be analyzed due to the inability of the laboratory at which the analysis was to be performed to conduct these assays, as a result of cuts in CDC funding.	NA mg/butt Standard Error NA Data for this measure will not be analyzed due to the inability of the laboratory at which the analysis was to be performed to conduct these assays, as a result of cuts in CDC funding.

SECONDARY outcome

Timeframe: Post-randomization study visits at study weeks 4, 8, 12

Population: Analysis consists of those participants who contributed data to the study through at least study week 4.

Difference between average puff volume per cigarette at laboratory smoking topography sessions at study weeks 4, 8, and 12 across all participants, comparing those assigned to the very-low-nicotine-content cigarette condition to those assigned to the normal-nicotine-content cigarette condition. Topography measures were averaged across all time points for each treatment group.

Outcome measures

Measure	Very Low Nicotine Content Cigarettes n=99 Participants Very low nicotine content cigarettes: 0.07 mg nicotine delivery	Normal Nicotine Content Cigarettes n=101 Participants Normal nicotine content cigarettes: 0.8 mg nicotine delivery
Exposure Measure - Smoking Topography	501.20 mL Standard Error 13.5	539.70 mL Standard Error 12.83

SECONDARY outcome

Timeframe: Post-randomization office visits weeks 2 (end of baseline period) and 12 (end of study)

Cotinine nicotine exposure measure, analyzed from urine samples taken at study office visits

The natural logarithm (ln) of the cotinine measures was used for analysis.

Difference in ln(cotinine) between baseline and end of study, from imputed data

Outcome measures

Measure	Very Low Nicotine Content Cigarettes n=118 Participants Very low nicotine content cigarettes: 0.07 mg nicotine delivery	Normal Nicotine Content Cigarettes n=120 Participants Normal nicotine content cigarettes: 0.8 mg nicotine delivery
Exposure Measure - Cotinine (Logged)	-0.84 log ng/mL Interval -1.29 to -0.39	-0.15 log ng/mL Interval -0.49 to 0.18

SECONDARY outcome

Timeframe: Entire length of study, through completion, up to 12 weeks

Population: Analysis population consists of those participants who contributed data to the study for (at minimum) the two-week baseline study period block as well as the first two-week block post-randomization

Mean mass smoked per cigarette (calculated as the starting cigarette weight minus returned butt weight) aggregated for all cigarettes smoked among participants assigned to the very-low-nicotine-content cigarette, compared to those assigned to the normal-nicotine-content cigarette condition.

Outcome measures

Measure	Very Low Nicotine Content Cigarettes n=111 Participants Very low nicotine content cigarettes: 0.07 mg nicotine delivery	Normal Nicotine Content Cigarettes n=114 Participants Normal nicotine content cigarettes: 0.8 mg nicotine delivery
Exposure Measure - Cigarette Butt Weight	0.58 grams Standard Error 0.01	0.60 grams Standard Error 0.01

Adverse Events

Very Low Nicotine Content Cigarettes

Serious events: 1 serious events

Other events: 41 other events

Deaths: 0 deaths

Normal Nicotine Content Cigarettes

Serious events: 2 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Measure	Very Low Nicotine Content Cigarettes n=118 participants at risk Very low nicotine content cigarettes: 0.07 mg nicotine delivery	Normal Nicotine Content Cigarettes n=120 participants at risk Normal nicotine content cigarettes: 0.8 mg nicotine delivery
General disorders Hospitalization for acute change in mental status (tranisient, unknown etiology)	0.00% 0/118 • Adverse event data was collected for each participant during the time of enrollment to completion of the study. Enrollment of study participants began in June 2015 and data collection concluded in July 2017. Thus, adverse event data for the entire study was collected over a 26 month span. Each individual participant participated in the study for 12 weeks. Adverse events were assessed during study visits via in-session interactions in which study participants were prompted to describe their experiences since the prior visit in an open-ended form, as well as via the self-completed Respiratory Health Questionnaire administered to participants at study visits.	0.83% 1/120 • Number of events 1 • Adverse event data was collected for each participant during the time of enrollment to completion of the study. Enrollment of study participants began in June 2015 and data collection concluded in July 2017. Thus, adverse event data for the entire study was collected over a 26 month span. Each individual participant participated in the study for 12 weeks. Adverse events were assessed during study visits via in-session interactions in which study participants were prompted to describe their experiences since the prior visit in an open-ended form, as well as via the self-completed Respiratory Health Questionnaire administered to participants at study visits.
Nervous system disorders Hospitalization for mini-seizures	0.00% 0/118 • Adverse event data was collected for each participant during the time of enrollment to completion of the study. Enrollment of study participants began in June 2015 and data collection concluded in July 2017. Thus, adverse event data for the entire study was collected over a 26 month span. Each individual participant participated in the study for 12 weeks. Adverse events were assessed during study visits via in-session interactions in which study participants were prompted to describe their experiences since the prior visit in an open-ended form, as well as via the self-completed Respiratory Health Questionnaire administered to participants at study visits.	0.83% 1/120 • Number of events 1 • Adverse event data was collected for each participant during the time of enrollment to completion of the study. Enrollment of study participants began in June 2015 and data collection concluded in July 2017. Thus, adverse event data for the entire study was collected over a 26 month span. Each individual participant participated in the study for 12 weeks. Adverse events were assessed during study visits via in-session interactions in which study participants were prompted to describe their experiences since the prior visit in an open-ended form, as well as via the self-completed Respiratory Health Questionnaire administered to participants at study visits.
Psychiatric disorders Hospitalization for psychiatric medication management	0.85% 1/118 • Number of events 1 • Adverse event data was collected for each participant during the time of enrollment to completion of the study. Enrollment of study participants began in June 2015 and data collection concluded in July 2017. Thus, adverse event data for the entire study was collected over a 26 month span. Each individual participant participated in the study for 12 weeks. Adverse events were assessed during study visits via in-session interactions in which study participants were prompted to describe their experiences since the prior visit in an open-ended form, as well as via the self-completed Respiratory Health Questionnaire administered to participants at study visits.	0.00% 0/120 • Adverse event data was collected for each participant during the time of enrollment to completion of the study. Enrollment of study participants began in June 2015 and data collection concluded in July 2017. Thus, adverse event data for the entire study was collected over a 26 month span. Each individual participant participated in the study for 12 weeks. Adverse events were assessed during study visits via in-session interactions in which study participants were prompted to describe their experiences since the prior visit in an open-ended form, as well as via the self-completed Respiratory Health Questionnaire administered to participants at study visits.

Other adverse events

Measure	Very Low Nicotine Content Cigarettes n=118 participants at risk Very low nicotine content cigarettes: 0.07 mg nicotine delivery	Normal Nicotine Content Cigarettes n=120 participants at risk Normal nicotine content cigarettes: 0.8 mg nicotine delivery
Respiratory, thoracic and mediastinal disorders Respiratory (cough, cold)	28.0% 33/118 • Adverse event data was collected for each participant during the time of enrollment to completion of the study. Enrollment of study participants began in June 2015 and data collection concluded in July 2017. Thus, adverse event data for the entire study was collected over a 26 month span. Each individual participant participated in the study for 12 weeks. Adverse events were assessed during study visits via in-session interactions in which study participants were prompted to describe their experiences since the prior visit in an open-ended form, as well as via the self-completed Respiratory Health Questionnaire administered to participants at study visits.	25.0% 30/120 • Adverse event data was collected for each participant during the time of enrollment to completion of the study. Enrollment of study participants began in June 2015 and data collection concluded in July 2017. Thus, adverse event data for the entire study was collected over a 26 month span. Each individual participant participated in the study for 12 weeks. Adverse events were assessed during study visits via in-session interactions in which study participants were prompted to describe their experiences since the prior visit in an open-ended form, as well as via the self-completed Respiratory Health Questionnaire administered to participants at study visits.
Gastrointestinal disorders Nausea / flu	1.7% 2/118 • Adverse event data was collected for each participant during the time of enrollment to completion of the study. Enrollment of study participants began in June 2015 and data collection concluded in July 2017. Thus, adverse event data for the entire study was collected over a 26 month span. Each individual participant participated in the study for 12 weeks. Adverse events were assessed during study visits via in-session interactions in which study participants were prompted to describe their experiences since the prior visit in an open-ended form, as well as via the self-completed Respiratory Health Questionnaire administered to participants at study visits.	6.7% 8/120 • Adverse event data was collected for each participant during the time of enrollment to completion of the study. Enrollment of study participants began in June 2015 and data collection concluded in July 2017. Thus, adverse event data for the entire study was collected over a 26 month span. Each individual participant participated in the study for 12 weeks. Adverse events were assessed during study visits via in-session interactions in which study participants were prompted to describe their experiences since the prior visit in an open-ended form, as well as via the self-completed Respiratory Health Questionnaire administered to participants at study visits.
Immune system disorders Seasonal allergies	6.8% 8/118 • Adverse event data was collected for each participant during the time of enrollment to completion of the study. Enrollment of study participants began in June 2015 and data collection concluded in July 2017. Thus, adverse event data for the entire study was collected over a 26 month span. Each individual participant participated in the study for 12 weeks. Adverse events were assessed during study visits via in-session interactions in which study participants were prompted to describe their experiences since the prior visit in an open-ended form, as well as via the self-completed Respiratory Health Questionnaire administered to participants at study visits.	7.5% 9/120 • Adverse event data was collected for each participant during the time of enrollment to completion of the study. Enrollment of study participants began in June 2015 and data collection concluded in July 2017. Thus, adverse event data for the entire study was collected over a 26 month span. Each individual participant participated in the study for 12 weeks. Adverse events were assessed during study visits via in-session interactions in which study participants were prompted to describe their experiences since the prior visit in an open-ended form, as well as via the self-completed Respiratory Health Questionnaire administered to participants at study visits.
Nervous system disorders Headache	0.85% 1/118 • Adverse event data was collected for each participant during the time of enrollment to completion of the study. Enrollment of study participants began in June 2015 and data collection concluded in July 2017. Thus, adverse event data for the entire study was collected over a 26 month span. Each individual participant participated in the study for 12 weeks. Adverse events were assessed during study visits via in-session interactions in which study participants were prompted to describe their experiences since the prior visit in an open-ended form, as well as via the self-completed Respiratory Health Questionnaire administered to participants at study visits.	0.83% 1/120 • Adverse event data was collected for each participant during the time of enrollment to completion of the study. Enrollment of study participants began in June 2015 and data collection concluded in July 2017. Thus, adverse event data for the entire study was collected over a 26 month span. Each individual participant participated in the study for 12 weeks. Adverse events were assessed during study visits via in-session interactions in which study participants were prompted to describe their experiences since the prior visit in an open-ended form, as well as via the self-completed Respiratory Health Questionnaire administered to participants at study visits.
Gastrointestinal disorders Acid reflux	0.85% 1/118 • Adverse event data was collected for each participant during the time of enrollment to completion of the study. Enrollment of study participants began in June 2015 and data collection concluded in July 2017. Thus, adverse event data for the entire study was collected over a 26 month span. Each individual participant participated in the study for 12 weeks. Adverse events were assessed during study visits via in-session interactions in which study participants were prompted to describe their experiences since the prior visit in an open-ended form, as well as via the self-completed Respiratory Health Questionnaire administered to participants at study visits.	0.00% 0/120 • Adverse event data was collected for each participant during the time of enrollment to completion of the study. Enrollment of study participants began in June 2015 and data collection concluded in July 2017. Thus, adverse event data for the entire study was collected over a 26 month span. Each individual participant participated in the study for 12 weeks. Adverse events were assessed during study visits via in-session interactions in which study participants were prompted to describe their experiences since the prior visit in an open-ended form, as well as via the self-completed Respiratory Health Questionnaire administered to participants at study visits.

Additional Information

Dr. Saul Shiffman

University of Pittsburgh

Phone: 412-567-1761

Email: shiffman@pinneyassociates.com

Results disclosure agreements

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