CLINICAL TRIALS PROFILE FOR NICOTINE

505(b)(2) Clinical Trials for NICOTINE

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
OTC	NCT00405912 ↗	St. John's Wort for Tobacco Cessation	Completed	National Cancer Institute (NCI)	Phase 2	2005-09-01	After a steady decline for the last 50 years, the prevalence of tobacco use in the United States has reached a plateau of approximately 23%. Currently available treatments among adults are expensive and not efficacious for all tobacco users. New pharmacologic agents need to be developed and tested to achieve the Healthy People 2010 goal of less than a 12% adult tobacco use prevalence. Bupropion, an FDA approved agent for tobacco cessation, acts by inhibiting central synaptosomal reuptake of dopamine and norepinephrine. A widely used herbal antidepressant, St. John's Wort (SJW), shares a similar mechanism of action and is effective for treating mild to moderate depression. SJW is well tolerated, available over the counter, and is significantly less expensive than the established treatments for tobacco dependence. To date, no prospective clinical trial evaluating the efficacy of SJW for the treatment of tobacco use has been published. We propose to evaluate the efficacy of SJW for increasing tobacco abstinence and decreasing nicotine withdrawal symptoms in a randomized, double-blind, placebo-controlled, three-arm, parallel group, dose-ranging clinical trial. Participants (N=120) will be randomly assigned to one of the three groups and will receive a twelve-week course of SJW 900 mg per day, 1800 mg per day, or a matching placebo. This study is anticipated to provide the data needed to develop a larger randomized controlled clinical trial submitted through the R01 funding mechanism.
OTC	NCT00224419 ↗	Testing Pharmacological Therapies for Pregnant Smokers	Terminated	National Cancer Institute (NCI)	Phase 4	2003-06-01	Nicotine dependence has not been sufficiently addressed in current state-of-the-science cessation interventions for pregnant smokers. The weight of the evidence from the general population of smokers suggests that nicotine replacement therapies may be beneficial cessation aids for pregnant smokers who are unable to stop smoking. The tremendous potential of these therapies for promoting smoking cessation among pregnant women creates a pressing need for decision tools and protocols to encourage treatment adherence that is essential for rigorous evaluation of the effectiveness of OTC NRT when provided as part of prenatal care. The results of this research could be directly translated to the improvement of obstetrical care providers' clinical practices. Medically supervised use of OTC NRT by pregnant smokers is an alternative to continued smoking that has the potential to substantially increase rates of smoking cessation during pregnancy.
OTC	NCT00224419 ↗	Testing Pharmacological Therapies for Pregnant Smokers	Terminated	Duke University	Phase 4	2003-06-01	Nicotine dependence has not been sufficiently addressed in current state-of-the-science cessation interventions for pregnant smokers. The weight of the evidence from the general population of smokers suggests that nicotine replacement therapies may be beneficial cessation aids for pregnant smokers who are unable to stop smoking. The tremendous potential of these therapies for promoting smoking cessation among pregnant women creates a pressing need for decision tools and protocols to encourage treatment adherence that is essential for rigorous evaluation of the effectiveness of OTC NRT when provided as part of prenatal care. The results of this research could be directly translated to the improvement of obstetrical care providers' clinical practices. Medically supervised use of OTC NRT by pregnant smokers is an alternative to continued smoking that has the potential to substantially increase rates of smoking cessation during pregnancy.

All Clinical Trials for NICOTINE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000284 ↗	Role of Metabolites in Nicotine Dependence (1) - 1	Completed	University of Minnesota	Phase 2	1995-02-01	The purpose of this study is to determine the effects of cotinine with or without a transdermal nicotine replacement on tobacco withdrawal symptoms.
NCT00000284 ↗	Role of Metabolites in Nicotine Dependence (1) - 1	Completed	University of Minnesota - Clinical and Translational Science Institute	Phase 2	1995-02-01	The purpose of this study is to determine the effects of cotinine with or without a transdermal nicotine replacement on tobacco withdrawal symptoms.
NCT00000284 ↗	Role of Metabolites in Nicotine Dependence (1) - 1	Completed	National Institute on Drug Abuse (NIDA)	Phase 2	1995-02-01	The purpose of this study is to determine the effects of cotinine with or without a transdermal nicotine replacement on tobacco withdrawal symptoms.

Clinical Trial Conditions for NICOTINE

Condition Name

Condition Name for NICOTINE
Intervention	Trials
Smoking Cessation	205
Nicotine Dependence	142
Smoking	113

Condition MeSH

Condition MeSH for NICOTINE
Intervention	Trials
Tobacco Use Disorder	310
Schizophrenia	55
Alcoholism	39

Clinical Trial Locations for NICOTINE

Trials by Country

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−

Trials by Country for NICOTINE
Location	Trials
Canada	53
Sweden	29
France	26
Germany	18
China	11

Trials by US State

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−

Trials by US State for NICOTINE
Location	Trials
California	89
Connecticut	74
Minnesota	65
Pennsylvania	64
North Carolina	60

Clinical Trial Progress for NICOTINE

Clinical Trial Phase

Clinical Trial Phase for NICOTINE
Clinical Trial Phase	Trials
Phase 4	175
Phase 3	91
Phase 2/Phase 3	26

Clinical Trial Status

Clinical Trial Status for NICOTINE
Clinical Trial Phase	Trials
Completed	620
Recruiting	96
Not yet recruiting	76

Clinical Trial Sponsors for NICOTINE

Sponsor Name

Sponsor Name for NICOTINE
Sponsor	Trials
National Institute on Drug Abuse (NIDA)	203
National Cancer Institute (NCI)	82
Yale University	61

Sponsor Type

Sponsor Type for NICOTINE
Sponsor	Trials
Other	1121
NIH	396
Industry	199

Nicotine and Smoking Cessation: Clinical Trials, Market Analysis, and Projections

Introduction to Nicotine and Smoking Cessation

Nicotine, a highly addictive substance found in tobacco, has been the focus of numerous efforts to develop effective smoking cessation treatments. With the rising health concerns associated with smoking and the growing demand for safer alternatives, the market for nicotine-based products and smoking cessation therapies is undergoing significant changes.

Clinical Trials Update: Cytisinicline

One of the most promising developments in smoking cessation is the clinical trials of cytisinicline, a medication being developed by Achieve Life Sciences.

ORCA-OL Clinical Trial

The ORCA-OL clinical trial is a crucial step in the development of cytisinicline. This open-label trial, initiated in May 2024, aims to provide long-term safety exposure data for cytisinicline in subjects who currently smoke or use nicotine e-cigarettes. The trial is being conducted at 29 sites across the United States and involves participants from previous ORCA Phase 2 and Phase 3 trials who have relapsed or continued to smoke or vape[1].

Phase 3 Clinical Trials

Previous Phase 3 clinical trials have shown cytisinicline to be effective and well-tolerated. A multi-site randomized placebo-controlled study involving 810 adult cigarette smokers demonstrated a statistically significant increase in biochemically confirmed continuous abstinence for six months. There were no reports of drug-related serious adverse side effects, highlighting the safety profile of cytisinicline[4].

Market Analysis: Smoking Cessation and Nicotine Addiction

The market for smoking cessation and nicotine addiction treatments is growing, driven by increasing R&D activities, healthcare spending, and the launch of emerging therapies.

Current Market Size

As of 2022, the smoking cessation and nicotine addiction market size in the 7MM (the United States, EU-4, the United Kingdom, and Japan) was approximately USD 2.3 billion. The market is projected to grow positively due to the expected launch of new therapies and increasing healthcare spending[3].

Emerging Therapies

Several companies, including Achieve Life Sciences, NFL Biosciences SAS, Embera NeuroTherapeutics, Inc, and Axsome Therapeutics, are developing novel smoking cessation and nicotine addiction drugs. Cytisinicline, in particular, is expected to address the unmet needs in the market, offering a potential new treatment option with a favorable safety profile and efficacy[3].

Market Projections: Nicotine Pouches and Alternatives

Nicotine Pouches Market

The nicotine pouches market is experiencing rapid growth, driven by consumer demand for safer alternatives to smoking.

U.S. Market

In the United States, the nicotine pouches market was estimated at USD 4.09 billion in 2024 and is expected to grow at a CAGR of 29.6% from 2025 to 2030. The demand for synthetic nicotine pouches is particularly strong, with a CAGR of 46.5% during the same period. Original/unflavored nicotine pouches and those with a 3mg concentration are also seeing significant growth, driven by health-conscious consumers seeking to quit smoking[2].

Global Market

Globally, the nicotine pouches market was estimated at USD 3.95 billion in 2024 and is projected to grow at a CAGR of 34.4% from 2025 to 2030. The Asia Pacific region, particularly China and India, is expected to see substantial growth due to regulatory measures against traditional tobacco products and increasing health concerns[5].

Consumer Trends and Preferences

Health-Conscious Consumers

There is a growing trend among consumers to seek safer alternatives to smoking. According to the CDC, nearly 67.7% of adults in the U.S. want to quit smoking, and approximately half have tried to quit in the past year. This has led to an increased demand for nicotine pouches and other tobacco-free products[2].

Online Sales

The sales of nicotine pouches through online channels are expected to grow significantly, with a CAGR of 44.0% from 2025 to 2030. This is driven by the convenience and accessibility of online platforms, as well as the availability of products directly from brands’ websites[5].

Challenges and Opportunities

Regulatory Environment

The regulatory environment plays a crucial role in the growth of the nicotine pouches market. Tightening regulations on traditional tobacco products in countries like China have led to an increase in the sales of alternative products, including nicotine pouches[5].

Healthcare Practitioner Training

Despite the growth in the market, there is a lack of appropriate training for healthcare practitioners to provide effective cessation interventions. This is a significant challenge that needs to be addressed to fully leverage the potential of new smoking cessation therapies[3].

Key Takeaways

• Cytisinicline: Clinical trials have shown cytisinicline to be effective and well-tolerated, with potential approval in the first half of 2025.
• Market Growth: The smoking cessation and nicotine addiction market is projected to grow positively, driven by emerging therapies and increasing healthcare spending.
• Nicotine Pouches: The U.S. and global nicotine pouches markets are experiencing rapid growth, driven by consumer demand for safer alternatives to smoking.
• Consumer Trends: Health-conscious consumers are driving the demand for nicotine pouches and other tobacco-free products.
• Regulatory Environment: Regulatory measures against traditional tobacco products are boosting the sales of alternative products.

FAQs

What is cytisinicline, and how does it work?

Cytisinicline is a smoking cessation medication that works by binding to nicotine receptors in the brain, reducing the urge to smoke. It is being developed by Achieve Life Sciences and has shown promising results in clinical trials.

How big is the nicotine pouches market in the U.S.?

The U.S. nicotine pouches market was estimated at USD 4.09 billion in 2024 and is expected to grow at a CAGR of 29.6% from 2025 to 2030.

What are the main drivers of the nicotine pouches market growth?

The main drivers include increasing consumer awareness, rising demand for cigarette smoking alternatives, diverse product offerings, and various strength formulations appealing to different consumers.

Are there any new treatments approved for smoking cessation in recent years?

No, there have been no new treatments approved by the FDA for smoking cessation in nearly two decades. However, cytisinicline is expected to be submitted for FDA approval in the first half of 2025.

How does the regulatory environment impact the nicotine pouches market?

Tightening regulations on traditional tobacco products have led to an increase in the sales of alternative products, including nicotine pouches, as consumers seek safer alternatives.

Sources

1. Achieve Life Sciences Announces Initiation of ORCA-OL Clinical Trial Evaluating Long-Term Exposure of Cytisinicline in People who Smoke or Use Nicotine E-Cigarettes. GlobeNewswire.
2. U.S. Nicotine Pouches Market Size | Industry Report, 2030. Grand View Research.
3. Smoking Cessation and Nicotine Addiction Market is Projected to Grow at a CAGR of 2.6 During the Study Period 2019-2032. DelveInsight via PR Newswire.
4. First large U.S. clinical trial of cytisinicline finds the smoking cessation medication effective and well-tolerated. Massachusetts General Hospital.
5. Nicotine Pouches Market Size & Share | Industry Report 2030. Grand View Research.