Flavored Nicotine Pouches for Smoking Reduction

Overseen By Hui Cheng, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Altria Client Services LLC

Must not be taking: Antipsychotics, Mood stabilizers

Disqualifiers: Cardiovascular disease, Cancer, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks

400 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn about the role of flavored on!® nicotine pouch products (the research products), an oral tobacco-leaf-free product, in the replacement of cigarettes with the use of the research products among adults who smoke cigarettes. The main question it aims to answer is whether flavored (vs. non-flavored) research products generate greater reduction of cigarette smoking among adults who smoke cigarettes. Participants will be provided with research products to use for 6 weeks. Researchers will compare the reduction in cigarette smoking between participants with access to a complete flavor profile of research products and participants with access to only the Original (non-flavored) variety of research product to see if reduction in cigarette smoking is greater among those with access to flavored research products.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those taking psychoactive medications like antipsychotics or mood stabilizers.

What data supports the effectiveness of the treatment Flavored on!® Nicotine Pouch Products for smoking reduction?

Research suggests that switching from cigarettes to flavored nicotine pouches may reduce harm for smokers who can't or don't want to quit smoking. Flavored nicotine pouches are popular among young adults and may encourage smokers to switch from cigarettes to these pouches. ^{1 2 3 4 5}

Is it safe to use flavored nicotine pouches for smoking reduction?

Research suggests that flavored nicotine pouches might be a lower-risk alternative to smoking cigarettes, but there is limited data on their safety. More studies are needed to fully understand their potential harms and benefits. ^{1 6 7 8 9}

How do flavored on!® nicotine pouches differ from other smoking reduction treatments?

Flavored on!® nicotine pouches are unique because they are tobacco-free, oral products that come in various flavors and nicotine strengths, offering a potentially lower-risk alternative to traditional cigarettes and tobacco-based products. Unlike other smoking reduction treatments, these pouches do not contain tobacco leaves and are designed to reduce harm for smokers who cannot or do not want to quit smoking entirely. ^{1 3 5 6 9}

Research Team

Hui Cheng, PhD

Principal Investigator

ALCS

Eligibility Criteria

Adults aged 22-65 who smoke at least 5 cigarettes daily for the past year, want to switch to a smoke-free tobacco product, and can use a smartphone with text and data. Excluded are those in poor health or with certain medical conditions, involved in tobacco litigation or industry, pregnant/nursing women not using birth control, heavy marijuana users, and recent participants in other tobacco studies.

Inclusion Criteria

I do not plan to use FDA-approved nicotine treatments soon.

Willing and able to comply with the requirements of the study.

Owns a smart phone with text message and data capabilities compatible with necessary surveys.

Exclusion Criteria

I cannot read, speak, or understand English.

I have used or am using nicotine pouch products.

I am taking medication for mental health issues.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline

Participants are followed for 3-7 days to establish baseline measures of cigarettes smoked per day, with at least two CO readings collected

1 week

Daily surveys

Treatment

Participants use research products for 6 weeks, with different access to flavors based on group assignment

6 weeks

Weekly surveys

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a 6-month follow-up survey

6 months

1 survey (virtual)

Treatment Details

Interventions

• Flavored on!® Nicotine Pouch Products

Trial Overview The trial is testing if flavored nicotine pouches (Berry, Citrus, Cinnamon etc.) help smokers reduce cigarette use more than non-flavored pouches over six weeks. Participants will be given these products to see if flavors lead to greater smoking reduction compared to just the Original flavor.

Participant Groups

Group I: Complete flavor profile of on! nicotine pouches Experimental Treatment 1 Intervention

This study arm will provided with access to all varieties of 4mg on! nicotine pouch products throughout the trial.

Group II: Non-Flavored then complete flavor on! nicotine pouches Active Control 1 Intervention

This study arm will provided with access to non-flavored (i.e., Original) 4mg on! nicotine pouch products during the first 3 weeks of the trial and then access to all varieties of 4mg on! nicotine pouch products during the last 3 weeks of the trial.

Group III: Non-Flavored on! nicotine pouches only Active Control 1 Intervention

This study arm will provided with access to non-flavored (i.e., Original) 4mg on! nicotine pouch products throughout the trial.

Flavored on!® Nicotine Pouch Products is already approved in United States, Canada, United Kingdom for the following indications:

Approved in United States as on! for:

• Not yet authorized by FDA; PMTA submitted

Approved in Canada as Zonnic Nicotine Pouches for:

• Authorized as a natural health product with 4mg of nicotine

Approved in United Kingdom as Nicotine Pouches for:

• Regulated under general consumer product safety regulations

Who Is Running the Clinical Trial?

Altria Client Services LLC

Lead Sponsor

Trials

10

Recruited

1,900+

Rose Research Center, LLC

Industry Sponsor

Trials

17

Recruited

1,600+

Findings from Research

In a study involving adult smokers, nicotine pouches (NPs) showed lower peak nicotine levels (Cmax) and longer time to peak (tmax) compared to traditional cigarettes, indicating a slower nicotine delivery.

Participants reported lower cravings for cigarettes when using NPs, suggesting that these products may have a lower abuse potential and could serve as a safer alternative for smokers looking to switch from cigarettes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine pharmacokinetics and subjective response among adult smokers using different flavors of on!® nicotine pouches compared to combustible cigarettes. Rensch, J., Liu, J., Wang, J., et al.[2021]

Adult tobacco users perceive oral nicotine pouches (ONPs) as significantly less harmful and less addictive compared to non-users, indicating a potential misperception of risk among users.

The displayed nicotine concentration on ONP packaging significantly influences perceptions of harm and addictiveness, with higher concentrations leading to lower perceived risks, suggesting that packaging features could impact public health perceptions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Oral Nicotine Pouch Packaging Features on Adult Tobacco Users' and Non-Users' Product Perceptions. Mays, D., Long, L., Alalwan, MA., et al.[2023]

In a study involving 30 adult smokers, 6-mg oral nicotine pouches (ONPs) delivered more nicotine to the bloodstream at 30 minutes compared to both 3-mg ONPs and cigarettes, suggesting they can be effective for nicotine delivery.

However, neither concentration of ONPs provided as much relief from cravings at 5 minutes as cigarettes did, indicating that while ONPs may be less harmful, they might not satisfy cravings as effectively, which could influence their potential for misuse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the effects of nicotine concentration on the appeal and nicotine delivery of oral nicotine pouches among rural and Appalachian adults who smoke cigarettes: A randomized cross-over study. Keller-Hamilton, B., Alalwan, MA., Curran, H., et al.[2023]

Oral Nicotine Pouches (ONPs) are gaining popularity, especially among adolescents and young adults, with over 50% of users preferring flavored options like menthol, fruity, and dessert flavors, which may encourage smokers to switch from cigarettes.

The study identified 152 natural and 228 synthetic ONP products, revealing that while tobacco and menthol flavors dominate natural ONPs, fruity and menthol flavors are most common in synthetic ONPs, raising concerns about potential health risks due to their chemical composition and effects on cellular signaling pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Classification, Perception, and Toxicity of Emerging Flavored Oral Nicotine Pouches. Shaikh, SB., Newton, C., Tung, WC., et al.[2023]

A study analyzing 653 Reddit posts about oral nicotine pouches revealed that users predominantly shared positive experiences and product information, indicating a favorable public perception of these tobacco-free products.

The discussions also highlighted a significant interest in quitting traditional nicotine products, with 12.7% of posts focused on using oral nicotine pouches as a cessation tool, suggesting potential for these pouches in harm reduction strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perceptions of Oral Nicotine Pouches on Reddit: Observational Study. Shao, Y., Zou, J., Xie, Z., et al.[2022]

In early 2021, only 29.2% of adult smokers were aware of nicotine pouches, with just 5.6% having tried them, indicating limited familiarity with this tobacco product category.

Interest in using nicotine pouches was notably higher among younger smokers (ages 18-44) and those planning to quit smoking, suggesting that these products may appeal more to individuals looking for alternatives to traditional tobacco.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine pouch product awareness, interest and ever use among US adults who smoke, 2021. Hrywna, M., Gonsalves, NJ., Delnevo, CD., et al.[2023]

Nicotine pouch use in Great Britain is currently rare, with a prevalence of only 0.26% among adults, but it has doubled from November 2020 to October 2021, indicating a growing interest in these products.

The use of nicotine pouches is significantly more common among men, current smokers, and users of other nicotine products like e-cigarettes and nicotine replacement therapies, suggesting that these pouches may appeal more to those already familiar with nicotine consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tobacco-free Nicotine Pouch Use in Great Britain: A Representative Population Survey 2020-2021. Tattan-Birch, H., Jackson, SE., Dockrell, M., et al.[2022]

Nicotine pouches, a new product category, are being marketed with minimal research and regulatory oversight, highlighting significant gaps in understanding their potential harms and benefits.

The commentary suggests a comprehensive assessment approach to inform regulatory policies, aiming to enhance public health outcomes while reducing unintended negative effects associated with nicotine pouch use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The New Nicotine Pouch Category: A Tobacco Harm Reduction Tool? Patwardhan, S., Fagerström, K.[2023]

ZYN nicotine pouches contain no nitrosamines or polycyclic aromatic hydrocarbons (PAHs), indicating a potentially lower risk profile compared to traditional tobacco products, which often contain harmful constituents.

The levels of harmful and potentially harmful constituents (HPHCs) in ZYN were found to be similar to those in nicotine replacement therapy (NRT) products, suggesting that ZYN may be a safer alternative for nicotine delivery compared to moist snuff, which had significantly higher levels of harmful compounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Harmful and potentially harmful constituents (HPHCs) in two novel nicotine pouch products in comparison with regular smokeless tobacco products and pharmaceutical nicotine replacement therapy products (NRTs). Back, S., Masser, AE., Rutqvist, LE., et al.[2023]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Nicotine pharmacokinetics and subjective response among adult smokers using different flavors of on!® nicotine pouches compared to combustible cigarettes. [2021]

2. Switzerland pubmed.ncbi.nlm.nih.gov

The Effects of Oral Nicotine Pouch Packaging Features on Adult Tobacco Users' and Non-Users' Product Perceptions. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Evaluating the effects of nicotine concentration on the appeal and nicotine delivery of oral nicotine pouches among rural and Appalachian adults who smoke cigarettes: A randomized cross-over study. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Classification, Perception, and Toxicity of Emerging Flavored Oral Nicotine Pouches. [2023]

5. Canada pubmed.ncbi.nlm.nih.gov

Perceptions of Oral Nicotine Pouches on Reddit: Observational Study. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Nicotine pouch product awareness, interest and ever use among US adults who smoke, 2021. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Tobacco-free Nicotine Pouch Use in Great Britain: A Representative Population Survey 2020-2021. [2022]

8. England pubmed.ncbi.nlm.nih.gov

The New Nicotine Pouch Category: A Tobacco Harm Reduction Tool? [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Harmful and potentially harmful constituents (HPHCs) in two novel nicotine pouch products in comparison with regular smokeless tobacco products and pharmaceutical nicotine replacement therapy products (NRTs). [2023]