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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether flavored nicotine pouches help people who smoke reduce their cigarette use more effectively than non-flavored pouches. Participants will try different nicotine pouch varieties, including flavored and non-flavored options, over six weeks. It targets adults who smoke at least five cigarettes a day and are interested in smoke-free alternatives without plans to quit nicotine entirely in the next two months. As an unphased trial, this study offers participants a unique opportunity to explore new smoke-free alternatives and contribute to research that could benefit others seeking similar options.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies have shown that nicotine pouches, such as flavored on!® nicotine pouches, are generally safer than traditional tobacco products. Because these pouches are tobacco-free and not burned, they pose a lower health risk compared to smoking cigarettes. Research indicates that these pouches do not contain the harmful chemicals found in tobacco smoke, suggesting they might be a less risky option for those looking to reduce or quit smoking.

Although nicotine pouches are considered a safer choice, they are not risk-free. They still contain nicotine, which is addictive. Additionally, they are not recommended for certain groups, such as young people, pregnant women, or those who have never used nicotine before. Overall, users of nicotine pouches have found them to be well-tolerated, with fewer harmful effects than smoking cigarettes. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about flavored nicotine pouches because they offer a potentially more appealing alternative for those trying to reduce smoking. Unlike traditional nicotine replacement therapies like patches, gums, or lozenges that often have a bland taste, these pouches come in a variety of flavors, which may enhance user satisfaction and adherence. Additionally, these pouches provide a discreet and convenient way to consume nicotine without inhaling harmful smoke, potentially lowering health risks associated with smoking. By offering diverse flavor options, these pouches could also address individual preferences more effectively, making the transition away from smoking easier for many users.

What evidence suggests that flavored nicotine pouches could be effective for smoking reduction?

This trial will compare different nicotine pouch options for smoking reduction. Research has shown that flavored nicotine pouches can help people smoke fewer cigarettes. One study found that these pouches deliver nicotine quickly, potentially satisfying cravings better than non-flavored options. Flavors seem to make the switch from cigarettes to pouches more appealing, possibly leading to reduced cigarette consumption. Reviews suggest that nicotine pouches might be a less harmful option for those not ready to quit smoking completely. Overall, flavored nicotine pouches appear promising in helping adult smokers reduce their cigarette use. ^{6 7 8 9 10}

Who Is on the Research Team?

Hui Cheng, PhD

Principal Investigator

ALCS

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

Citations

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This study will provide empirical evidence about the effect that flavor availability in smoke-free products may have in reducing cigarette smoking.

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