Informing Oral Nicotine Pouch Regulations to Promote Public Health

NCT06315881 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: OSU-23116NCI-2024-00666U54CA287392
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

This clinical trial evaluates the characteristics of oral nicotine pouches (ONPs) to determine if they are a comparable substitute to cigarette or smokeless tobacco (ST) products. ONPs contain nicotine but no tobacco and are used primarily by adult tobacco uses in the United States (US). ONPs are recognized by the Food and Drug Administration as having lower risk than combustible cigarettes and are approved as a modified risk tobacco product. While ONPs have lower toxic risk than other tobacco products, acute and longer term harm related to their use has not been studied. Information gathered from this study may identify product characteristics of ONPs that improve successful switching from high-risk cigarettes or ST to lower risk ONPs.

Conditions

Tobacco-Related Carcinoma

Outcome Measures

Primary Outcomes (5)

• Increased nicotine delivery

  Data will be used to assess the effects of nicotine concentration, form and isomer on the addiction potential and appeal of oral nicotine pouches (ONPs) relative to cigarettes and smokeless tobacco (ST). Generalized mixed effects models will be used to assess differences between the four ONP conditions and the usual product.

  Up to 3 months

• Liking

  Data will be used to assess the effects of nicotine concentration, form and isomer on the addiction potential and appeal of ONPs relative to cigarettes and ST. Generalized mixed effects models will be used to assess differences between the four ONP conditions and the usual product.

  Up to 3 months

• Craving/withdrawal suppression

  Data will be used to assess the effects of nicotine concentration, form and isomer on the addiction potential and appeal of ONPs relative to cigarettes and ST. Generalized mixed effects models will be used to assess differences between the four ONP conditions and the usual product.

  Up to 3 months

• Rate of switching to ONP

  Data will be used to assess the effects of nicotine concentration, form and isomer on the addiction potential and appeal of ONPs relative to cigarettes and ST. Generalized mixed effects models will be used to assess differences between the four ONP conditions and the usual product.

  Up to 3 months

• Rate of switching to ONPs

  Data will be used to evaluate the effects of nicotine concentration, form and isomer on switching from cigarettes or ST to ONPs either partially or completely. Logistic regression models will be used to examine whether differences in form and isomer significantly impact switching.

  Up to 3 months

Secondary Outcomes (1)

• ONP and Tobacco Purchase Task

  Up to 3 months

Study Arms (9)

PHASE I ARM I (low FBN R/S ONP)

EXPERIMENTAL

Participants insert low free-base nicotine (FBN) R/S ONP product over 30 minutes and insert usual brand of ST over 30 minutes or smoke usual brand of cigarette over 5 minutes during each study visit for 5 visits over up to 3 months. Patients also undergo blood sample collection throughout study.

Procedure: Biospecimen Collection; Drug: Cigarette; Drug: Nicotine Oral Pouch; Drug: Smokeless Tobacco; Other: Survey Administration

PHASE I ARM II (low FBN > 99% S ONP)

EXPERIMENTAL

Participants insert low FBN \> 99% S ONP product over 30 minutes and insert usual brand of ST over 30 minutes or smoke usual brand of cigarette over 5 minutes during each study visit for 5 visits over up to 3 months. Patients also undergo blood sample collection throughout study.

Procedure: Biospecimen Collection; Drug: Cigarette; Drug: Nicotine Oral Pouch; Drug: Smokeless Tobacco; Other: Survey Administration

PHASE I ARM III (high FBN R/S ONP)

EXPERIMENTAL

Participants insert high R/S ONP product over 30 minutes and insert usual brand of ST over 30 minutes or smoke usual brand of cigarette over 5 minutes during each study visit for 5 visits over up to 3 months. Patients also undergo blood sample collection throughout study.

Procedure: Biospecimen Collection; Drug: Cigarette; Drug: Nicotine Oral Pouch; Drug: Smokeless Tobacco; Other: Survey Administration

PHASE I ARM IV (high FBN > 99% ONP)

EXPERIMENTAL

Participants insert high FBN \> 99% S ONP product over 30 minutes and insert usual brand of ST over 30 minutes or smoke usual brand of cigarette over 5 minutes during each study visit for 5 visits over up to 3 months. Patients also undergo blood sample collection throughout study.

Procedure: Biospecimen Collection; Drug: Cigarette; Drug: Nicotine Oral Pouch; Drug: Smokeless Tobacco; Other: Survey Administration

PHASE I ARM V (Usual brand ST or cigarette)

EXPERIMENTAL

Participants insert usual brand of ST over 30 minutes or smoke usual brand of cigarette over 5 minutes. Patients also undergo blood sample collection at 0, 5, 15, 30, 60, and 90 minutes.

Procedure: Biospecimen Collection; Drug: Cigarette; Drug: Smokeless Tobacco; Other: Survey Administration

PHASE II ARM I (low FBN R/S ONP)

EXPERIMENTAL

WASHOUT PERIOD: Participants use usual brand of ST or cigarettes for 1 week. CONTROL WEEK: Participants continue regular use of ST or cigarettes for 1 week and receive a text with a link to daily diary surveys to record tobacco use. Participants insert low FBN R/S ONP for 4 weeks. Participants also attend 2 study visits and undergo oral mucosa sample collection.

Procedure: Biospecimen Collection; Drug: Cigarette; Drug: Nicotine Oral Pouch; Drug: Smokeless Tobacco; Other: Survey Administration; Other: Text Message-Based Navigation Intervention

PHASE II ARM II (low FBN > 99% S ONP)

EXPERIMENTAL

WASHOUT PERIOD: Participants use usual brand of ST or cigarettes for 1 week. CONTROL WEEK: Participants continue regular use of ST or cigarettes for 1 week and receive a text with a link to daily diary surveys to record tobacco use. Participants insert to low FBN \> 99% S ONP product for 4 weeks. Participants also attend 2 study visits and undergo oral mucosa sample collection.

Procedure: Biospecimen Collection; Drug: Cigarette; Drug: Nicotine Oral Pouch; Drug: Smokeless Tobacco; Other: Survey Administration; Other: Text Message-Based Navigation Intervention

PHASE II ARM III (high R/S ONP)

EXPERIMENTAL

WASHOUT PERIOD: Participants use usual brand of ST or cigarettes for 1 week. CONTROL WEEK: Participants continue regular use of ST or cigarettes for 1 week and receive a text with a link to daily diary surveys to record tobacco use. Participants insert to high R/S ONP product for 4 weeks. Participants also attend 2 study visits and undergo oral mucosa sample collection.

Procedure: Biospecimen Collection; Drug: Cigarette; Drug: Nicotine Oral Pouch; Drug: Smokeless Tobacco; Other: Survey Administration; Other: Text Message-Based Navigation Intervention

PHASE II ARM IV (high FBN > 99% ONP)

EXPERIMENTAL

WASHOUT PERIOD: Participants use usual brand of ST or cigarettes for 1 week. CONTROL WEEK: Participants continue regular use of ST or cigarettes for 1 week and receive a text with a link to daily diary surveys to record tobacco use. Participants insert high FBN \> 99% S ONP product for 4 weeks. Participants also attend 2 study visits and undergo oral mucosa sample collection.

Procedure: Biospecimen Collection; Drug: Cigarette; Drug: Nicotine Oral Pouch; Drug: Smokeless Tobacco; Other: Survey Administration; Other: Text Message-Based Navigation Intervention

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample and oral mucosa sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

PHASE I ARM I (low FBN R/S ONP); PHASE I ARM II (low FBN > 99% S ONP); PHASE I ARM III (high FBN R/S ONP); PHASE I ARM IV (high FBN > 99% ONP); PHASE I ARM V (Usual brand ST or cigarette); PHASE II ARM I (low FBN R/S ONP); PHASE II ARM II (low FBN > 99% S ONP); PHASE II ARM III (high R/S ONP); PHASE II ARM IV (high FBN > 99% ONP)

Cigarette DRUG

Smoke usual brand cigarette

PHASE I ARM I (low FBN R/S ONP); PHASE I ARM II (low FBN > 99% S ONP); PHASE I ARM III (high FBN R/S ONP); PHASE I ARM IV (high FBN > 99% ONP); PHASE I ARM V (Usual brand ST or cigarette); PHASE II ARM I (low FBN R/S ONP); PHASE II ARM II (low FBN > 99% S ONP); PHASE II ARM III (high R/S ONP); PHASE II ARM IV (high FBN > 99% ONP)

Nicotine Oral Pouch DRUG

Insert low FBN R/S ONP

Also known as: ZYN

PHASE I ARM I (low FBN R/S ONP); PHASE II ARM I (low FBN R/S ONP)

Smokeless Tobacco DRUG

Insert ST

Also known as: Smoking, Tobacco and Cancer - Smokeless Tobacco

PHASE I ARM I (low FBN R/S ONP); PHASE I ARM II (low FBN > 99% S ONP); PHASE I ARM III (high FBN R/S ONP); PHASE I ARM IV (high FBN > 99% ONP); PHASE I ARM V (Usual brand ST or cigarette); PHASE II ARM I (low FBN R/S ONP); PHASE II ARM II (low FBN > 99% S ONP); PHASE II ARM III (high R/S ONP); PHASE II ARM IV (high FBN > 99% ONP)

Survey Administration OTHER

Ancillary studies

PHASE I ARM I (low FBN R/S ONP); PHASE I ARM II (low FBN > 99% S ONP); PHASE I ARM III (high FBN R/S ONP); PHASE I ARM IV (high FBN > 99% ONP); PHASE I ARM V (Usual brand ST or cigarette); PHASE II ARM I (low FBN R/S ONP); PHASE II ARM II (low FBN > 99% S ONP); PHASE II ARM III (high R/S ONP); PHASE II ARM IV (high FBN > 99% ONP)

Text Message-Based Navigation Intervention OTHER

Receive text with a link to daily diary surveys

Also known as: Automated Text Message-Based Navigation, Text Message-Based Navigation

PHASE II ARM I (low FBN R/S ONP); PHASE II ARM II (low FBN > 99% S ONP); PHASE II ARM III (high R/S ONP); PHASE II ARM IV (high FBN > 99% ONP)

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Read and speak English
• At least 21 years old
• Willing to provide informed consent and abstain from all tobacco, nicotine, and marijuana use for at least 12 hours prior to Phase 1 study visits
• Willing to attend all study visits and use study ONPs
• Owns a smartphone and able to receive short messaging service (SMS) text messages with embedded survey link (for daily diary reports of ONP and other tobacco use)
• Negative pregnancy test produced during Phase 1 visits 1-5 and Phase 2 visit 1 if capable of becoming pregnant
• Exhaled carbon monoxide (CO) reading \< 10 (Phase 1)
• CIGARETTE SMOKERS ONLY: Established cigarette smoker (has smoked at least 100 cigarettes, has smoked daily for at least the past 3 months, now smokes at least 5 cigarettes per day)
• ST USERS ONLY: Established moist snuff user (has used moist snuff daily for at least the past 3 months, uses at least 1.5 cans/week (as in Pickworth et al., 2014)

You may not qualify if:

• Unstable or significant psychiatric conditions (past and stable conditions will be allowed)
• History of cardiac event or distress within the past 3 months
• Currently pregnant, planning to become pregnant, or breastfeeding (will be verified with urine pregnancy test before each Phase 1 study visit \[acute use of usual product and study ONPs\] and Phase 2 study visit 1 \[distribution of study ONPs for outpatient ad libitum use\])
• Currently engaging in tobacco quit attempt, interested in quitting all tobacco, or planning on quitting all tobacco in the next 3 months
• Oral or systemic health issues that affect oral microbiome or epithelium, including having fewer than 21 teeth, diabetes mellitus, or autoimmune disease (e.g., rheumatoid arthritis, lupus)
• CIGARETTE SMOKERS ONLY: Use of non-cigarette tobacco products ≥ 10 of the past 30 days
• CIGARETTE SMOKERS ONLY: Self-reported diagnosis of lung disease including asthma (if uncontrolled or worse than usual), cystic fibrosis, or chronic obstructive pulmonary disease
• CIGARETTE SMOKERS ONLY: Roll-your-own cigarette smokers
• ST USERS ONLY: Use of non-moist-snuff tobacco products ≥ 10 of the past 30 days

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Interventions

Specimen Handling; Tobacco Products; Tobacco, Smokeless

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Smoking Devices; Manufactured Materials; Technology, Industry, and Agriculture

Study Officials

• Brittney L Keller-Hamilton, PhD, MPH

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 14, 2024
• First Posted: March 18, 2024
• Study Start: January 13, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: April 27, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)