Trial Outcomes & Findings for Reduced Nicotine Cigarettes in Smokers With Mood and Anxiety Disorders (NCT NCT01928758)

NCT ID: NCT01928758

Last Updated: 2019-06-28

Results Overview

Plasma cotinine is a measure of daily nicotine exposure. Samples were measured in ng/mL.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 245 participants
• Primary outcome timeframe: Measured at the end of the last 3 weeks of randomization trial phase
• Results posted on: 2019-06-28

Participant Flow

27 participants attended Visit 1 and consented but did not meet final eligibility criteria. The remaining participants (n=218) began a baseline phase during which 30 participants were lost to follow up or withdrawn from the study before being randomized to the study intervention. 188 participants were randomized into an intervention.

Participant milestones

Measure	Reduced Nicotine Content Cigarettes The experimental group will smoke cigarettes with gradually Reduced Nicotine Content (11.6, 7.4, 3.3, 1.4, 0.7 and 0.2 mg per cigarette) cigarettes, with each nicotine level smoked for 3 weeks, except the lowest level which continues for 6 weeks Reduced Nicotine Content Cigarettes: Research cigarettes will have gradually reduced nicotine content	Usual Nicotine Content Cigarettes Research cigarettes with a nicotine content similar to participant's usual brand of cigarettes (around 11.6mg) Usual Nicotine Content Cigarettes: Usual Nicotine Content Cigarettes
Overall Study STARTED	94	94
Overall Study COMPLETED	69	74
Overall Study NOT COMPLETED	25	20

Reasons for withdrawal

Measure	Reduced Nicotine Content Cigarettes The experimental group will smoke cigarettes with gradually Reduced Nicotine Content (11.6, 7.4, 3.3, 1.4, 0.7 and 0.2 mg per cigarette) cigarettes, with each nicotine level smoked for 3 weeks, except the lowest level which continues for 6 weeks Reduced Nicotine Content Cigarettes: Research cigarettes will have gradually reduced nicotine content	Usual Nicotine Content Cigarettes Research cigarettes with a nicotine content similar to participant's usual brand of cigarettes (around 11.6mg) Usual Nicotine Content Cigarettes: Usual Nicotine Content Cigarettes
Overall Study Lost to Follow-up	14	9
Overall Study Withdrawal by Subject	5	2
Overall Study Adverse Event	3	5
Overall Study Protocol Violation	3	4

Baseline Characteristics

Reduced Nicotine Cigarettes in Smokers With Mood and Anxiety Disorders

Baseline characteristics by cohort

Measure	Reduced Nicotine Content Cigarettes n=94 Participants The experimental group will smoke cigarettes with gradually Reduced Nicotine Content (11.6, 7.4, 3.3, 1.4, 0.7 and 0.2 mg per cigarette) cigarettes, with each nicotine level smoked for 3 weeks, except the lowest level which continues for 6 weeks Reduced Nicotine Content Cigarettes: Research cigarettes will have gradually reduced nicotine content	Usual Nicotine Content Cigarettes n=94 Participants Research cigarettes with a nicotine content similar to participant's usual brand of cigarettes (around 11.6mg) Usual Nicotine Content Cigarettes: Usual Nicotine Content Cigarettes	Total n=188 Participants Total of all reporting groups
Age, Continuous	43.3 years STANDARD_DEVIATION 11.7 • n=5 Participants	43.1 years STANDARD_DEVIATION 13.3 • n=7 Participants	43.2 years STANDARD_DEVIATION 12.5 • n=5 Participants
Sex: Female, Male Female	60 Participants n=5 Participants	54 Participants n=7 Participants	114 Participants n=5 Participants
Sex: Female, Male Male	34 Participants n=5 Participants	40 Participants n=7 Participants	74 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	87 Participants n=5 Participants	93 Participants n=7 Participants	180 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian/white	70 Participants n=5 Participants	76 Participants n=7 Participants	146 Participants n=5 Participants
Race/Ethnicity, Customized African American/black	15 Participants n=5 Participants	11 Participants n=7 Participants	26 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Island	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian/Alaskan native	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Other	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Region of Enrollment United States	94 participants n=5 Participants	94 participants n=7 Participants	188 participants n=5 Participants
Menthol smoker	38 Participants n=5 Participants	36 Participants n=7 Participants	74 Participants n=5 Participants
Quick Inventory of Depressive Symptomatology	5.5 units on a scale STANDARD_DEVIATION 4.8 • n=5 Participants	6.3 units on a scale STANDARD_DEVIATION 4.3 • n=7 Participants	5.9 units on a scale STANDARD_DEVIATION 4.5 • n=5 Participants
Perceived Stress Scale	16.0 units on a scale STANDARD_DEVIATION 7.5 • n=5 Participants	17.1 units on a scale STANDARD_DEVIATION 8.2 • n=7 Participants	16.5 units on a scale STANDARD_DEVIATION 7.9 • n=5 Participants
Overall Anxiety Severity and Impairment Scale	4.9 units on a scale STANDARD_DEVIATION 4.1 • n=5 Participants	5.7 units on a scale STANDARD_DEVIATION 4.3 • n=7 Participants	5.3 units on a scale STANDARD_DEVIATION 4.2 • n=5 Participants
Kessler-6 Scale	5.6 units on a scale STANDARD_DEVIATION 5.4 • n=5 Participants	6.5 units on a scale STANDARD_DEVIATION 5.1 • n=7 Participants	6.1 units on a scale STANDARD_DEVIATION 5.3 • n=5 Participants
Cigarettes per day	20.2 cigarettes STANDARD_DEVIATION 10.7 • n=5 Participants	21.6 cigarettes STANDARD_DEVIATION 10.6 • n=7 Participants	20.9 cigarettes STANDARD_DEVIATION 10.7 • n=5 Participants
Exhaled Carbon Monoxide	29.4 parts per million STANDARD_DEVIATION 17.7 • n=5 Participants	29.1 parts per million STANDARD_DEVIATION 15.1 • n=7 Participants	29.3 parts per million STANDARD_DEVIATION 16.4 • n=5 Participants
Plasma Cotinine	245.7 ng/mL STANDARD_DEVIATION 137.2 • n=5 Participants	255.9 ng/mL STANDARD_DEVIATION 145.5 • n=7 Participants	250.9 ng/mL STANDARD_DEVIATION 141.2 • n=5 Participants
Minnesota Nicotine Withdrawal Scale	9.9 units on a scale STANDARD_DEVIATION 7.3 • n=5 Participants	10.5 units on a scale STANDARD_DEVIATION 6.3 • n=7 Participants	10.2 units on a scale STANDARD_DEVIATION 6.8 • n=5 Participants

PRIMARY outcome

Timeframe: Measured at the end of the last 3 weeks of randomization trial phase

Population: Randomized trial phase completers with non-missing values for the outcome at both time points being used in the regression (complete case analysis).

Plasma cotinine is a measure of daily nicotine exposure. Samples were measured in ng/mL.

Outcome measures

Measure	Usual Nicotine Content Cigarettes n=72 Participants Research cigarettes with a usual nicotine content (around 11.6mg per cigarette) Usual Nicotine Content Cigarettes: Usual Nicotine Content Cigarettes	Reduced Nicotine Content Cigarettes n=66 Participants The experimental group will smoke cigarettes with gradually Reduced Nicotine Content (11.6, 7.4, 3.3, 1.4, 0.7 and 0.2 mg per cigarette) cigarettes, with each nicotine level smoked for 3 weeks, except the lowest level which continues for 6 weeks Reduced Nicotine Content Cigarettes: Research cigarettes will have gradually reduced nicotine content
Plasma Cotinine Concentration	259.0 ng/mL Standard Deviation 151.3	82.8 ng/mL Standard Deviation 154.3

SECONDARY outcome

Timeframe: Measured at the end of the last 3 weeks of randomization trial phase

Population: Randomized trial phase completers with non-missing values for the outcome at both time points being used in the regression (complete case analysis).

A 16-item scale on depression symptoms. The scale range is 0-27 where 0 = Least Severe and 27 = Most Severe.

Outcome measures

Measure	Usual Nicotine Content Cigarettes n=72 Participants Research cigarettes with a usual nicotine content (around 11.6mg per cigarette) Usual Nicotine Content Cigarettes: Usual Nicotine Content Cigarettes	Reduced Nicotine Content Cigarettes n=69 Participants The experimental group will smoke cigarettes with gradually Reduced Nicotine Content (11.6, 7.4, 3.3, 1.4, 0.7 and 0.2 mg per cigarette) cigarettes, with each nicotine level smoked for 3 weeks, except the lowest level which continues for 6 weeks Reduced Nicotine Content Cigarettes: Research cigarettes will have gradually reduced nicotine content
Quick Inventory of Depressive Symptomatology	5.3 score on a scale Standard Deviation 3.9	5.5 score on a scale Standard Deviation 4.3

SECONDARY outcome

Timeframe: Measured at the end of the last 3 weeks of randomization trial phase

Population: Randomized trial phase completers with non-missing values for the outcome at both time points being used in the regression (complete case analysis).

10-item questionnaire measuring the degree to which life situations are appraised stressful. Scale range is 0-40. Higher scores indicate more stress.

Outcome measures

Measure	Usual Nicotine Content Cigarettes n=74 Participants Research cigarettes with a usual nicotine content (around 11.6mg per cigarette) Usual Nicotine Content Cigarettes: Usual Nicotine Content Cigarettes	Reduced Nicotine Content Cigarettes n=69 Participants The experimental group will smoke cigarettes with gradually Reduced Nicotine Content (11.6, 7.4, 3.3, 1.4, 0.7 and 0.2 mg per cigarette) cigarettes, with each nicotine level smoked for 3 weeks, except the lowest level which continues for 6 weeks Reduced Nicotine Content Cigarettes: Research cigarettes will have gradually reduced nicotine content
Perceived Stress Scale	15.1 score on a scale Standard Deviation 7.8	15.0 score on a scale Standard Deviation 7.6

SECONDARY outcome

Timeframe: Measured at the end of the last 3 weeks of randomization trial phase

Population: Randomized trial phase completers with non-missing values for the outcome at both time points being used in the regression (complete case analysis).

This 8-item scale measures nicotine withdrawal symptoms and the scale range is from 0-32. Higher scores indicate higher severity.

Outcome measures

Measure	Usual Nicotine Content Cigarettes n=74 Participants Research cigarettes with a usual nicotine content (around 11.6mg per cigarette) Usual Nicotine Content Cigarettes: Usual Nicotine Content Cigarettes	Reduced Nicotine Content Cigarettes n=69 Participants The experimental group will smoke cigarettes with gradually Reduced Nicotine Content (11.6, 7.4, 3.3, 1.4, 0.7 and 0.2 mg per cigarette) cigarettes, with each nicotine level smoked for 3 weeks, except the lowest level which continues for 6 weeks Reduced Nicotine Content Cigarettes: Research cigarettes will have gradually reduced nicotine content
Minnesota Nicotine Withdrawal Scale	9.0 score on a scale Standard Deviation 5.9	8.1 score on a scale Standard Deviation 6.8

OTHER_PRE_SPECIFIED outcome

Timeframe: At end of 18-week randomized trial phase

Population: Participants who attended the visit at the end of the 18-week randomized trial phase

Smokers assigned to the reduced nicotine content cigarette group may have lower perceived dependence and be more likely to report intention to quit smoking

Outcome measures

Measure	Usual Nicotine Content Cigarettes n=74 Participants Research cigarettes with a usual nicotine content (around 11.6mg per cigarette) Usual Nicotine Content Cigarettes: Usual Nicotine Content Cigarettes	Reduced Nicotine Content Cigarettes n=69 Participants The experimental group will smoke cigarettes with gradually Reduced Nicotine Content (11.6, 7.4, 3.3, 1.4, 0.7 and 0.2 mg per cigarette) cigarettes, with each nicotine level smoked for 3 weeks, except the lowest level which continues for 6 weeks Reduced Nicotine Content Cigarettes: Research cigarettes will have gradually reduced nicotine content
Intention to Quit Smoking	25 Participants	33 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Follow-up appointment 30 weeks after randomization (12 weeks after last visit of randomized trial phase).

Population: All randomized participants

Smokers assigned to reduced nicotine content cigarettes will be more likely to successfully abstain from smoking at the end of the trial, based on all randomized participants, defined as no cigarette use in past 7 days, verified by exhaled carbon monoxide <10ppm.

Outcome measures

Measure	Usual Nicotine Content Cigarettes n=94 Participants Research cigarettes with a usual nicotine content (around 11.6mg per cigarette) Usual Nicotine Content Cigarettes: Usual Nicotine Content Cigarettes	Reduced Nicotine Content Cigarettes n=94 Participants The experimental group will smoke cigarettes with gradually Reduced Nicotine Content (11.6, 7.4, 3.3, 1.4, 0.7 and 0.2 mg per cigarette) cigarettes, with each nicotine level smoked for 3 weeks, except the lowest level which continues for 6 weeks Reduced Nicotine Content Cigarettes: Research cigarettes will have gradually reduced nicotine content
Abstinence From Smoking	4 Participants	17 Participants

Adverse Events

Reduced Nicotine Content Cigarettes

Serious events: 7 serious events

Other events: 70 other events

Deaths: 0 deaths

Usual Nicotine Content Cigarettes

Serious events: 10 serious events

Other events: 72 other events

Deaths: 0 deaths

Serious adverse events

Measure	Reduced Nicotine Content Cigarettes n=94 participants at risk The experimental group will smoke cigarettes with gradually Reduced Nicotine Content (11.6, 8.6, 4.0, 1.8, 0.9 and 0.3 mg per cigarette) cigarettes, with each nicotine level smoked for 3 weeks, except the lowest level which continues for 6 weeks Reduced Nicotine Content Cigarettes: Research cigarettes will have gradually reduced nicotine content	Usual Nicotine Content Cigarettes n=94 participants at risk Research cigarettes with a nicotine content similar to participant's usual brand of cigarettes (around 11.6mg) Usual Nicotine Content Cigarettes: Usual Nicotine Content Cigarettes
Infections and infestations Appendicitis	1.1% 1/94 • Number of events 1 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.00% 0/94 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Cardiac disorders Cardiac disorders - Other	1.1% 1/94 • Number of events 1 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.00% 0/94 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Psychiatric disorders Depression	1.1% 1/94 • Number of events 1 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	1.1% 1/94 • Number of events 1 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Respiratory, thoracic and mediastinal disorders Dyspnea	0.00% 0/94 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	1.1% 1/94 • Number of events 1 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Infections and infestations Endocarditis infective	0.00% 0/94 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	1.1% 1/94 • Number of events 1 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Injury, poisoning and procedural complications Fracture	1.1% 1/94 • Number of events 1 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.00% 0/94 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Cardiac disorders Heart failure	0.00% 0/94 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	1.1% 1/94 • Number of events 1 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Infections and infestations Infections and infestations - Other	1.1% 1/94 • Number of events 1 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	1.1% 1/94 • Number of events 1 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Injury, poisoning and procedural complications Injury, poisoning and procedural complications - Other	0.00% 0/94 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	1.1% 1/94 • Number of events 1 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Musculoskeletal and connective tissue disorders Musculoskeletal and connective tissue disorder - Other	0.00% 0/94 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	1.1% 1/94 • Number of events 1 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Psychiatric disorders Psychiatric disorders - Other	0.00% 0/94 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	1.1% 1/94 • Number of events 1 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other	0.00% 0/94 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	1.1% 1/94 • Number of events 1 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Psychiatric disorders Suicidal ideation	1.1% 1/94 • Number of events 1 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.00% 0/94 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Surgical and medical procedures Surgical and medical procedures - Other	0.00% 0/94 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	1.1% 1/94 • Number of events 1 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Infections and infestations Upper respiratory infection	1.1% 1/94 • Number of events 1 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	0.00% 0/94 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Cardiac disorders Acute coronary syndrome	0.00% 0/94 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	1.1% 1/94 • Number of events 1 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Cardiac disorders Aortic valve disease	0.00% 0/94 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	1.1% 1/94 • Number of events 1 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.

Other adverse events

Measure	Reduced Nicotine Content Cigarettes n=94 participants at risk The experimental group will smoke cigarettes with gradually Reduced Nicotine Content (11.6, 8.6, 4.0, 1.8, 0.9 and 0.3 mg per cigarette) cigarettes, with each nicotine level smoked for 3 weeks, except the lowest level which continues for 6 weeks Reduced Nicotine Content Cigarettes: Research cigarettes will have gradually reduced nicotine content	Usual Nicotine Content Cigarettes n=94 participants at risk Research cigarettes with a nicotine content similar to participant's usual brand of cigarettes (around 11.6mg) Usual Nicotine Content Cigarettes: Usual Nicotine Content Cigarettes
Respiratory, thoracic and mediastinal disorders Allergic rhinitis	6.4% 6/94 • Number of events 6 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	3.2% 3/94 • Number of events 3 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Psychiatric disorders Anxiety	23.4% 22/94 • Number of events 28 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	20.2% 19/94 • Number of events 22 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Musculoskeletal and connective tissue disorders Back pain	3.2% 3/94 • Number of events 4 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	6.4% 6/94 • Number of events 6 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Respiratory, thoracic and mediastinal disorders Cough	5.3% 5/94 • Number of events 5 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	5.3% 5/94 • Number of events 5 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Psychiatric disorders Depression	31.9% 30/94 • Number of events 39 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	22.3% 21/94 • Number of events 26 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
General disorders Flu like symptoms	9.6% 9/94 • Number of events 9 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	11.7% 11/94 • Number of events 14 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Nervous system disorders Headache	8.5% 8/94 • Number of events 9 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	4.3% 4/94 • Number of events 5 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Vascular disorders Hypertension	3.2% 3/94 • Number of events 3 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	7.4% 7/94 • Number of events 7 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Psychiatric disorders Irritability	4.3% 4/94 • Number of events 4 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	6.4% 6/94 • Number of events 7 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Musculoskeletal and connective tissue disorders Pain in extremity	5.3% 5/94 • Number of events 5 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	3.2% 3/94 • Number of events 3 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Respiratory, thoracic and mediastinal disorders Respiratory, thoracic and mediastinal disorders - Other	9.6% 9/94 • Number of events 13 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	13.8% 13/94 • Number of events 15 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Psychiatric disorders Suicidal ideation	14.9% 14/94 • Number of events 14 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	11.7% 11/94 • Number of events 11 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Surgical and medical procedures Surgical and medical procedures - Other	5.3% 5/94 • Number of events 5 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	5.3% 5/94 • Number of events 5 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.
Infections and infestations Upper respiratory infection	30.9% 29/94 • Number of events 32 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.	25.5% 24/94 • Number of events 30 • All randomized participants throughout the entire 33 weeks of the trial. Adverse events (AEs) were systematically collected at each study visit by asking participants about any changes in their physical or mental health or if they needed to seek immediate medical care at an emergency room or hospital.

Additional Information

Jonathan Foulds

Penn State College of Medicine

Phone: 717-531-3504

Email: jfoulds@psu.edu

Results disclosure agreements

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