Impact of Very Low Nicotine Content Cigarettes in a Complex Marketplace

NCT03272685 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 2017NTLS107
• Study Type: interventional
• Target: 799
• Locations: 1 country
• Sites: 6

Brief Summary

This project will examine the impact of very low nicotine content (VLNC) cigarettes in a complex tobacco and nicotine product marketplace. We will compare the number of cigarettes smoked and cigarette-free days in an experimental marketplace that contains VLNC cigarettes versus normal nicotine content (NNC) cigarettes.

Conditions

Tobacco Smoking; Nicotine Dependence

Keywords

Reduced nicotine cigarettes; Alternative nicotine products; Biomarkers of tobacco exposure

Outcome Measures

Primary Outcomes (2)

• Cigarettes Per Day (CPD)

  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).

  7 days prior to week 12 visit

• Number of Smoke-free Days

  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)

  day 1 of study until day before week 12 visit

Secondary Outcomes (3)

• Percent Change in 2-cyanoethyl-mercapturic Acid (CEMA)

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

• Study Cigarettes Per Day

  12 weeks (Phase 3) on study cigarettes

• Seven Day Point-prevalence CO-verified Abstinence

  7 days before week 12 visit

Study Arms (2)

Very Low Nicotine Content Cigarettes

EXPERIMENTAL

Very Low Nicotine Content Cigarettes (0.4 mg nicotine/g tobacco; 9 mg of tar): Median nicotine content, averaged across menthol and non-menthol cigarettes:

Drug: Very Low Nicotine Content Cigarettes

Normal Nicotine Content Cigarettes

ACTIVE COMPARATOR

Normal (Conventional) Nicotine Content (15.8 mg nicotine/g tobacco; 9 mg of tar): Median nicotine content, averaged across menthol and non-menthol cigarettes

Drug: Normal Nicotine Content Cigarettes

Interventions

Very Low Nicotine Content Cigarettes DRUG

0.4 mg nicotine/g tobacco; 9 mg tar

Also known as: Reduced Nicotine Content Cigarettes

Very Low Nicotine Content Cigarettes

Normal Nicotine Content Cigarettes DRUG

15.8 mg nicotine/g tobacco; 9 mg tar

Also known as: Conventional Nicotine Content Cigarettes

Normal Nicotine Content Cigarettes

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female;
• /21 (legal age to purchase tobacco at site);
• Biochemically confirmed smoker.

You may not qualify if:

• Unstable health condition;
• Unstable medications;
• Pregnant or nursing.

Sponsors & Collaborators

• University of Minnesota: lead
• Duke University: collaborator
• University of California, San Francisco: collaborator
• Wake Forest University: collaborator
• University of Pennsylvania: collaborator
• Brown University: collaborator

Study Sites (6)

Tobacco Research Center

San Francisco, California, 94110, United States

Location

Tobacco Research Programs

Minneapolis, Minnesota, 55414, United States

Location

The Center for Addiction Science and Technology

Durham, North Carolina, 27705, United States

Location

Wake Forest Tobacco Control Center of Excellence

Winston-Salem, North Carolina, 27175, United States

Location

Center for Interdisciplinary Research on Nicotine Addiction

Philadelphia, Pennsylvania, 19104, United States

Location

Brown University Center for Alcohol and Addiction Studies School of Public Health

Providence, Rhode Island, 02912, United States

Location

Related Publications (2)

• Said RJ, Carroll DM, Luo X, Hu J, Cao Q, Tessier KM, Bittencourt L, Hatsukami DK; Center for Evaluation of Nicotine in Cigarettes (CENIC). Secondary analysis of a randomized clinical trial of very low nicotine cigarettes: Outcomes across social and demographic groups. Prev Med. 2025 Dec;201:108362. doi: 10.1016/j.ypmed.2025.108362. Epub 2025 Jul 21.

  PMID: 40701191 DERIVED

• Hatsukami DK, Jensen JA, Carroll DM, Luo X, Strayer LG, Cao Q, Hecht SS, Murphy SE, Carmella SG, Denlinger-Apte RL, Colby S, Strasser AA, McClernon FJ, Tidey J, Benowitz NL, Donny EC. Reduced nicotine in cigarettes in a marketplace with alternative nicotine systems: randomized clinical trial. Lancet Reg Health Am. 2024 Jun 3;35:100796. doi: 10.1016/j.lana.2024.100796. eCollection 2024 Jul.

  PMID: 38911348 DERIVED

MeSH Terms

Conditions

Tobacco Smoking; Tobacco Use Disorder

Condition Hierarchy (Ancestors)

Smoking; Behavior; Tobacco Use; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Limitations and Caveats

1\. Simulated natural environment

Results Point of Contact

• Title: Dorothy Hatsukami
• Organization: University of Minnesota

hatsu001@umn.edu

612-626-2121

Study Officials

• Dorothy Hatsukami, PHD

  University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase III randomized, open label, multi-center study that will examine the impact of very low nicotine content (VLNC) cigarettes using an experimental marketplace that contains tobacco and nicotine products, simulating a real world environment. There are three phases: Phase 1 is smoking usual brand cigarettes. Phase 2 is access to a marketplace with usual brand cigarettes and other non-combusted nicotine and tobacco products. Phase 3 involves access to a marketplace with study cigarettes and other non-combusted nicotine and tobacco products.

Study Record Dates

• First Submitted: August 10, 2017
• First Posted: September 5, 2017
• Study Start: June 1, 2018
• Primary Completion: September 30, 2022
• Study Completion: January 10, 2023
• Last Updated: August 20, 2024
• Results First Posted: August 20, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Time Frame: Data will not be available until primary and secondary papers are accepted for publication.
• Access Criteria: Persons requesting data must do so in writing, identifying their affiliation and how the data will be used. Upon review, access will be determined.

Locations

US (6)