Trial Outcomes & Findings for Impact of Very Low Nicotine Content Cigarettes in a Complex Marketplace (NCT NCT03272685)

Last Updated: 2024-08-20

Results Overview

The mean cigarettes (study and non-study cigarettes) smoked per day based on 7 days Daily Interactive Voice Response (IVR) data at the end of Phase 3 (experimental marketplace with study cigarettes) compared to Phase 2 (experimental marketplace with usual brand cigarettes).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

799 participants

Primary outcome timeframe

7 days prior to week 12 visit

Results posted on

2024-08-20

Participant Flow

799 potential participants were consented and attended the screening visit. 535 eligible participants entered Phase 1; 491 continued on to Phase 2; 438 were randomized into Phase 3. See description of Phases under Study Description.

Participant milestones

Participant milestones
Measure	Very Low Nicotine Content Cigarettes Very Low Nicotine Content Cigarettes: 0.4 mg nicotine/g tobacco; 9 mg of tar	Normal Nicotine Content Cigarettes Normal (Conventional) Nicotine Content: 15.8 mg nicotine/g tobacco; 9 mg of tar
Overall Study STARTED	220	218
Overall Study COMPLETED	166	173
Overall Study NOT COMPLETED	54	45

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Impact of Very Low Nicotine Content Cigarettes in a Complex Marketplace

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Very Low Nicotine Content Cigarettes n=220 Participants Very low nicotine content cigarettes: 0.4 mg nicotine/g tobacco; 9 mg of tar	Normal Nicotine Content Cigarettes n=218 Participants Normal (Conventional) Nicotine Content: 15.8 mg nicotine/g tobacco; 9 mg of tar	Total n=438 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	212 Participants n=5 Participants	209 Participants n=7 Participants	421 Participants n=5 Participants
Age, Categorical >=65 years	8 Participants n=5 Participants	9 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Female	123 Participants n=5 Participants	102 Participants n=7 Participants	225 Participants n=5 Participants
Sex: Female, Male Male	97 Participants n=5 Participants	116 Participants n=7 Participants	213 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Asian	6 Participants n=5 Participants	7 Participants n=7 Participants	13 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	45 Participants n=5 Participants	54 Participants n=7 Participants	99 Participants n=5 Participants
Race (NIH/OMB) White	143 Participants n=5 Participants	139 Participants n=7 Participants	282 Participants n=5 Participants
Race (NIH/OMB) More than one race	21 Participants n=5 Participants	13 Participants n=7 Participants	34 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Cigarettes Per Day (CPD)	15.6 Number of Cigarettes Per Day STANDARD_DEVIATION 6.9 • n=5 Participants	15.5 Number of Cigarettes Per Day STANDARD_DEVIATION 7.6 • n=7 Participants	15.5 Number of Cigarettes Per Day STANDARD_DEVIATION 7.3 • n=5 Participants

PRIMARY outcome

Timeframe: 7 days prior to week 12 visit

Outcome measures

Outcome measures
Measure	Very Low Nicotine Content Cigarettes n=168 Participants Very Low Nicotine Content Cigarettes: 0.4 mg nicotine/g tobacco; 9 mg tar	Normal Nicotine Content Cigarettes n=173 Participants Normal Nicotine Content Cigarettes: 15.8 mg nicotine/g tobacco; 9 mg tar
Cigarettes Per Day (CPD)	7.05 cigarettes per day Standard Deviation 7.88	12.95 cigarettes per day Standard Deviation 9.07

PRIMARY outcome

Timeframe: day 1 of study until day before week 12 visit

Rate of smoke-free days, defined as no cigarettes smoked in the past 24 hours calculated as the proportion of smoke-free days out of the total number of days in Phase 3. Number of smoke free days based on the interactive voice response (IVR)

Outcome measures

Outcome measures
Measure	Very Low Nicotine Content Cigarettes n=218 Participants Very Low Nicotine Content Cigarettes: 0.4 mg nicotine/g tobacco; 9 mg tar	Normal Nicotine Content Cigarettes n=217 Participants Normal Nicotine Content Cigarettes: 15.8 mg nicotine/g tobacco; 9 mg tar
Number of Smoke-free Days	18.6 days Standard Deviation 28	5.1 days Standard Deviation 13.8

SECONDARY outcome

Timeframe: The last visit in Phase 2 is the end of the baseline

Change in CEMA (biomarker for the mercapturic acid acrylonitrile) from end of Phase 2 (experimental marketplace with usual brand cigarettes) to end of Phase 3 (experimental marketplace with study cigarettes).

Outcome measures

Outcome measures
Measure	Very Low Nicotine Content Cigarettes n=161 Participants Very Low Nicotine Content Cigarettes: 0.4 mg nicotine/g tobacco; 9 mg tar	Normal Nicotine Content Cigarettes n=170 Participants Normal Nicotine Content Cigarettes: 15.8 mg nicotine/g tobacco; 9 mg tar
Percent Change in 2-cyanoethyl-mercapturic Acid (CEMA)	-34 percentage of change Interval -82.0 to 21.0	8 percentage of change Interval -38.0 to 61.0

SECONDARY outcome

Timeframe: 12 weeks (Phase 3) on study cigarettes

The mean study cigarettes smoked per day based on 7 days Daily Interactive Voice Response (IVR) data at the end of Phase 3 (experimental marketplace with study cigarettes) compared to Phase 2 (experimental marketplace with usual brand cigarettes).

Outcome measures

Outcome measures
Measure	Very Low Nicotine Content Cigarettes n=168 Participants Very Low Nicotine Content Cigarettes: 0.4 mg nicotine/g tobacco; 9 mg tar	Normal Nicotine Content Cigarettes n=173 Participants Normal Nicotine Content Cigarettes: 15.8 mg nicotine/g tobacco; 9 mg tar
Study Cigarettes Per Day	5.33 cigarettes per day Standard Deviation 6.86	12.42 cigarettes per day Standard Deviation 9.23

SECONDARY outcome

Timeframe: 7 days before week 12 visit

Total cigarettes per day equal to 0 for all 7 days before the week 12 visit and carbon monoxide (CO) ≤ 6ppm at week 12.

Outcome measures

Outcome measures
Measure	Very Low Nicotine Content Cigarettes n=220 Participants Very Low Nicotine Content Cigarettes: 0.4 mg nicotine/g tobacco; 9 mg tar	Normal Nicotine Content Cigarettes n=218 Participants Normal Nicotine Content Cigarettes: 15.8 mg nicotine/g tobacco; 9 mg tar
Seven Day Point-prevalence CO-verified Abstinence	41 Participants	15 Participants

Adverse Events

Very Low Nicotine Content Cigarettes

Serious events: 7 serious events

Other events: 39 other events

Deaths: 0 deaths

Normal Nicotine Content Cigarettes

Serious events: 6 serious events

Other events: 42 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Very Low Nicotine Content Cigarettes n=220 participants at risk Very Low Nicotine Content Cigarettes: 0.4 mg nicotine/g tobacco; 9 mg of tar	Normal Nicotine Content Cigarettes n=218 participants at risk Normal (Conventional) Nicotine Content (15.8 mg/g nicotine/g tobacco; 9 mg of tar
General disorders Hospitalization	2.7% 6/220 • Number of events 6 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	2.8% 6/218 • Number of events 6 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer Diagnosis	0.45% 1/220 • Number of events 1 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	0.00% 0/218 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.

Other adverse events

Additional Information

Dorothy Hatsukami

University of Minnesota

Phone: 612-626-2121

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Very Low Nicotine Content Cigarettes n=220 participants at risk Very Low Nicotine Content Cigarettes: 0.4 mg nicotine/g tobacco; 9 mg of tar	Normal Nicotine Content Cigarettes n=218 participants at risk Normal (Conventional) Nicotine Content (15.8 mg/g nicotine/g tobacco; 9 mg of tar
Psychiatric disorders Elevated CES-D score	17.7% 39/220 • Number of events 40 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	19.3% 42/218 • Number of events 47 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.
Respiratory, thoracic and mediastinal disorders Cough	15.9% 35/220 • Number of events 37 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	9.2% 20/218 • Number of events 21 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.
General disorders Nasal congestion/Rhinorrhea	15.5% 34/220 • Number of events 38 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	9.6% 21/218 • Number of events 28 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.
General disorders Headache/Migraine	15.5% 34/220 • Number of events 38 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	7.8% 17/218 • Number of events 18 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.
Musculoskeletal and connective tissue disorders Myalgia	11.4% 25/220 • Number of events 29 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	10.1% 22/218 • Number of events 28 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.
General disorders Sore/Itchy/Irritated Throat	9.5% 21/220 • Number of events 23 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	6.0% 13/218 • Number of events 16 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.
General disorders Irritability/Frustration	9.1% 20/220 • Number of events 20 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	6.0% 13/218 • Number of events 13 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.
Social circumstances Stress	8.6% 19/220 • Number of events 19 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	6.4% 14/218 • Number of events 16 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.
Psychiatric disorders Depressed/Sad Mood	7.3% 16/220 • Number of events 18 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	7.3% 16/218 • Number of events 17 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.
General disorders Fever	8.6% 19/220 • Number of events 19 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	4.6% 10/218 • Number of events 10 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.
General disorders Anxious/Nervous	6.4% 14/220 • Number of events 14 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	6.4% 14/218 • Number of events 14 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.
General disorders Fatigue	5.9% 13/220 • Number of events 14 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	6.0% 13/218 • Number of events 14 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.
General disorders Increase in Phlegm	5.5% 12/220 • Number of events 12 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	5.0% 11/218 • Number of events 11 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.
General disorders Diarrhea	6.4% 14/220 • Number of events 16 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	2.8% 6/218 • Number of events 7 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.
General disorders Vomiting	5.5% 12/220 • Number of events 13 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	3.2% 7/218 • Number of events 7 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.
General disorders Toothache	2.7% 6/220 • Number of events 7 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	5.5% 12/218 • Number of events 13 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.
Respiratory, thoracic and mediastinal disorders Productive Cough/Lung Fullness	2.3% 5/220 • Number of events 5 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	5.0% 11/218 • Number of events 11 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.
General disorders Insomnia	5.0% 11/220 • Number of events 11 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	1.4% 3/218 • Number of events 3 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.
Infections and infestations Infection	5.0% 11/220 • Number of events 15 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.	1.4% 3/218 • Number of events 3 • Adverse Events reported during Phase 3 intervention regardless of relationship, up to a total of 12 weeks. Participants were queried for any medical care, health or medication changes since their last visit.