Trial Outcomes & Findings for Methods Project 4: Clinical Trial (NCT NCT01867242)

NCT ID: NCT01867242

Last Updated: 2023-05-03

Results Overview

Number of days subjects smoked no cigarettes during the intervention was compared between groups.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 150 participants
• Primary outcome timeframe: 8 weeks (56 (+/-5) days)
• Results posted on: 2023-05-03

Participant Flow

Smokers were recruited from Minneapolis, Minnesota; Columbus and Coshocton, Ohio, and Buffalo, New York between May 2013 and August 2016. Internet and local media advertisements read: "Smokers who want to try a new oral tobacco product are needed for a research study that may reduce their exposure to harmful tobacco smoke."

After 1 week, participants returned to the clinic with snus tins and unused snus pouches. Tobacco use over the past week was assessed and participants completed self-report questionnaires. Participants who used at least seven snus pouches (based on potential use of one pouch per day) and continued to smoke were eligible to enter the clinical trial. These criteria were withheld from participants to ensure an unbiased willingness to use snus.

Participant milestones

Measure	Complete Substitution Use snus in place of cigarettes Snus: Winterchill or Robust flavors	Partial Substitution (Snus and Cigarettes) Use snus and cigarettes how ever you like Cigarettes: Smoke their usual brand of cigarettes and follow their normal patterns of use. Snus: Winterchill or Robust flavors	Usual Brand Cigarette Smoking usual brand cigarette controls, who after 8-weeks will be offered Camel Snus and instructed for partial or complete substitution of cigarettes (subject's choice); Cigarettes: Smoke their usual brand of cigarettes and follow their normal patterns of use.
Overall Study STARTED	64	60	26
Overall Study COMPLETED	40	44	18
Overall Study NOT COMPLETED	24	16	8

Reasons for withdrawal

Measure	Complete Substitution Use snus in place of cigarettes Snus: Winterchill or Robust flavors	Partial Substitution (Snus and Cigarettes) Use snus and cigarettes how ever you like Cigarettes: Smoke their usual brand of cigarettes and follow their normal patterns of use. Snus: Winterchill or Robust flavors	Usual Brand Cigarette Smoking usual brand cigarette controls, who after 8-weeks will be offered Camel Snus and instructed for partial or complete substitution of cigarettes (subject's choice); Cigarettes: Smoke their usual brand of cigarettes and follow their normal patterns of use.
Overall Study Lost to follow-up, personal reasons	24	16	8

Baseline Characteristics

Methods Project 4: Clinical Trial

Baseline characteristics by cohort

Measure	Complete Substitution n=64 Participants Use snus in place of cigarettes Snus: Winterchill or Robust flavors	Partial Substitution (Snus and Cigarettes) n=60 Participants Use snus and cigarettes how ever you like Cigarettes: Smoke their usual brand of cigarettes and follow their normal patterns of use. Snus: Winterchill or Robust flavors	Usual Brand Cigarette n=26 Participants Smoking usual brand cigarette controls, who after 8-weeks will be offered Camel Snus and instructed for partial or complete substitution of cigarettes (subject's choice); Cigarettes: Smoke their usual brand of cigarettes and follow their normal patterns of use.	Total n=150 Participants Total of all reporting groups
Age, Continuous	42.5 years n=5 Participants	42.0 years n=7 Participants	47.0 years n=5 Participants	43.5 years n=4 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	24 Participants n=7 Participants	13 Participants n=5 Participants	65 Participants n=4 Participants
Sex: Female, Male Male	36 Participants n=5 Participants	36 Participants n=7 Participants	13 Participants n=5 Participants	85 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	16 Participants n=5 Participants	16 Participants n=7 Participants	11 Participants n=5 Participants	43 Participants n=4 Participants
Race (NIH/OMB) White	44 Participants n=5 Participants	43 Participants n=7 Participants	15 Participants n=5 Participants	102 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants
Region of Enrollment United States	64 participants n=5 Participants	60 participants n=7 Participants	26 participants n=5 Participants	150 participants n=4 Participants
Mean cigarettes per day (CPD)	14.0 Cigarettes Per Day n=5 Participants	11.7 Cigarettes Per Day n=7 Participants	12.1 Cigarettes Per Day n=5 Participants	12.3 Cigarettes Per Day n=4 Participants
Fagerstrom Test for Nicotine Dependence (FTND)	3.0 units on a scale n=5 Participants	3.0 units on a scale n=7 Participants	3.0 units on a scale n=5 Participants	3.0 units on a scale n=4 Participants
Total Nicotine Equivalents (TNE)	58.3 nmol/mg n=5 Participants	55.9 nmol/mg n=7 Participants	65.7 nmol/mg n=5 Participants	59.1 nmol/mg n=4 Participants

PRIMARY outcome

Timeframe: 8 weeks (56 (+/-5) days)

Number of days subjects smoked no cigarettes during the intervention was compared between groups.

Outcome measures

Measure	Complete Substitution n=64 Participants Use snus in place of cigarettes Snus: Winterchill or Robust flavors	Partial Substitution (Snus and Cigarettes) n=60 Participants Use snus and cigarettes how ever you like Cigarettes: Smoke their usual brand of cigarettes and follow their normal patterns of use. Snus: Winterchill or Robust flavors	Usual Brand Cigarette n=26 Participants Smoking usual brand cigarette controls, who after 8-weeks will be offered Camel Snus and instructed for partial or complete substitution of cigarettes (subject's choice); Cigarettes: Smoke their usual brand of cigarettes and follow their normal patterns of use.
Smoke-free Days	14.5 days Interval 0.0 to 61.0	0 days Interval 0.0 to 0.0	0 days Interval 0.0 to 0.0

SECONDARY outcome

Timeframe: 8 weeks

2-cyanoethylmercapturic acid (CEMA) is a biomarker for exposure to acrylonitrile, a volatile organic compound, and is sensitive to changes in cigarette smoke exposure.

Outcome measures

Measure	Complete Substitution n=24 Participants Use snus in place of cigarettes Snus: Winterchill or Robust flavors	Partial Substitution (Snus and Cigarettes) n=38 Participants Use snus and cigarettes how ever you like Cigarettes: Smoke their usual brand of cigarettes and follow their normal patterns of use. Snus: Winterchill or Robust flavors	Usual Brand Cigarette n=15 Participants Smoking usual brand cigarette controls, who after 8-weeks will be offered Camel Snus and instructed for partial or complete substitution of cigarettes (subject's choice); Cigarettes: Smoke their usual brand of cigarettes and follow their normal patterns of use.
CEMA (2-cyanoethylmercapturic Acid)	248.1 pmol/mg per creatinine Interval 142.7 to 431.2	438.8 pmol/mg per creatinine Interval 365.0 to 657.5	594.6 pmol/mg per creatinine Interval 441.9 to 800.0

SECONDARY outcome

Timeframe: 8 weeks

Urinary total nicotine equivalents, the molar sum of nicotine and six metabolites, accounts for more than 90% of a nicotine dose

Outcome measures

Measure	Complete Substitution n=24 Participants Use snus in place of cigarettes Snus: Winterchill or Robust flavors	Partial Substitution (Snus and Cigarettes) n=39 Participants Use snus and cigarettes how ever you like Cigarettes: Smoke their usual brand of cigarettes and follow their normal patterns of use. Snus: Winterchill or Robust flavors	Usual Brand Cigarette n=16 Participants Smoking usual brand cigarette controls, who after 8-weeks will be offered Camel Snus and instructed for partial or complete substitution of cigarettes (subject's choice); Cigarettes: Smoke their usual brand of cigarettes and follow their normal patterns of use.
Total Nicotine Exposure	46.7 nmol/mg Interval 32.5 to 67.0	65.0 nmol/mg Interval 53.1 to 79.4	63.4 nmol/mg Interval 42.7 to 94.0

SECONDARY outcome

Timeframe: 8 weeks

Urinary 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL) is a metabolite of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), one of the group of chemicals termed tobacco-specific N-nitrosamines (TSNA)

Outcome measures

Measure	Complete Substitution n=24 Participants Use snus in place of cigarettes Snus: Winterchill or Robust flavors	Partial Substitution (Snus and Cigarettes) n=39 Participants Use snus and cigarettes how ever you like Cigarettes: Smoke their usual brand of cigarettes and follow their normal patterns of use. Snus: Winterchill or Robust flavors	Usual Brand Cigarette n=16 Participants Smoking usual brand cigarette controls, who after 8-weeks will be offered Camel Snus and instructed for partial or complete substitution of cigarettes (subject's choice); Cigarettes: Smoke their usual brand of cigarettes and follow their normal patterns of use.
Urinary Total NNAL	1.43 pmol/mg creatinine Interval 1.07 to 1.91	1.27 pmol/mg creatinine Interval 1.01 to 1.61	1.38 pmol/mg creatinine Interval 0.91 to 2.08

Adverse Events

Complete Substitution

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Partial Substitution (Snus and Cigarettes)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Usual Brand Cigarette

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Complete Substitution n=64 participants at risk Substitute snus in place of all cigarettes Snus: Winterchill or Robust flavors	Partial Substitution (Snus and Cigarettes) n=60 participants at risk Substitute snus for cigarettes ad libitum Cigarettes: Smoke their usual brand of cigarettes and follow their normal patterns of use. Snus: Winterchill or Robust flavors	Usual Brand Cigarette n=26 participants at risk Smoking usual brand cigarette controls Cigarettes: Smoke their usual brand of cigarettes and follow their normal patterns of use.
Injury, poisoning and procedural complications Hospitalization	1.6% 1/64 • Number of events 1 • Adverse events related to study product reported over 8 weeks of snus product use.	0.00% 0/60 • Adverse events related to study product reported over 8 weeks of snus product use.	0.00% 0/26 • Adverse events related to study product reported over 8 weeks of snus product use.

Other adverse events

Measure	Complete Substitution n=64 participants at risk Substitute snus in place of all cigarettes Snus: Winterchill or Robust flavors	Partial Substitution (Snus and Cigarettes) n=60 participants at risk Substitute snus for cigarettes ad libitum Cigarettes: Smoke their usual brand of cigarettes and follow their normal patterns of use. Snus: Winterchill or Robust flavors	Usual Brand Cigarette n=26 participants at risk Smoking usual brand cigarette controls Cigarettes: Smoke their usual brand of cigarettes and follow their normal patterns of use.
Gastrointestinal disorders Hearburn/reflux	6.2% 4/64 • Number of events 4 • Adverse events related to study product reported over 8 weeks of snus product use.	1.7% 1/60 • Number of events 1 • Adverse events related to study product reported over 8 weeks of snus product use.	0.00% 0/26 • Adverse events related to study product reported over 8 weeks of snus product use.
Gastrointestinal disorders Nausea	6.2% 4/64 • Number of events 4 • Adverse events related to study product reported over 8 weeks of snus product use.	1.7% 1/60 • Number of events 1 • Adverse events related to study product reported over 8 weeks of snus product use.	0.00% 0/26 • Adverse events related to study product reported over 8 weeks of snus product use.
Gastrointestinal disorders Gum sensitivity	7.8% 5/64 • Number of events 5 • Adverse events related to study product reported over 8 weeks of snus product use.	1.7% 1/60 • Number of events 1 • Adverse events related to study product reported over 8 weeks of snus product use.	0.00% 0/26 • Adverse events related to study product reported over 8 weeks of snus product use.
Psychiatric disorders Irritability	4.7% 3/64 • Number of events 3 • Adverse events related to study product reported over 8 weeks of snus product use.	0.00% 0/60 • Adverse events related to study product reported over 8 weeks of snus product use.	0.00% 0/26 • Adverse events related to study product reported over 8 weeks of snus product use.

Additional Information

Dorothy Hatsukami, PhD

University of Minnesota

Phone: 612-626-2121

Email: hatsu001@umn.edu

Results disclosure agreements

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