About ORCA-3: A Clinical Study of Cytisinicline as a New Treatment Option to Help Adults Quit Smoking

Precision Clinical Research is participating in ORCA-3, a multicenter, double-blind, randomized, placebo-controlled phase 3 trial evaluating the efficacy and safety of cytisinicline in adult smokers.

ORCA-3 is being conducted to assess the effectiveness and safety of cytisinicline as a smoking cessation therapy in adults who smoke cigarettes. Cytisinicline is a naturally occurring, plant-based investigational treatment that is believed to aid in smoking cessation by reducing the severity of nicotine withdrawal symptoms.

Study Enrollment Criteria

To qualify for ORCA-3, participants must (be/have):

• Age ≥18 years
• Current daily cigarette smokers who smoke ten or more cigarettes per day and who intend to quit smoking
• Failed at least one previous attempt to stop smoking with or without therapeutic support
• Willing to set a quit date within 5-7 days of starting treatment
• Willing to actively participate in the study’s smoking cessation behavioral support provided throughout the study
• Doctors will check other requirements to confirm that participants qualify for this study.

Study Arms

Participants will be randomized to one of three study arms to determine the smoking cessation efficacy and safety profile of cytisinicline administered for either 6 or 12 weeks, compared to placebo. All participants will receive standard behavioral support and will be assigned to one of the following groups:

• Arm A: 12 weeks of placebo
• Arm B: 6 weeks of cytisinicline, followed by 6 weeks of placebo
• Arm C: 12 weeks of cytisinicline

If participants qualify for and enroll in this study, they may receive the following:

• Cytisinicline (study drug), or placebo
• Study-related medical tests
• Financial stipend to help with travel costs and time

All study medication and study-related care will be at no cost.

If you or someone you know is interested in joining the study, or would like to learn more, please call  954-440-7644 or apply online for enrollment.

Smoking Cessation: Background

A recent report showed that in 2020, for the first time in twenty years, there was an increase in cigarette purchases¹. Despite the clearly defined health risks associated with cigarette smoking, it is estimated that there are 34 million adults who are current cigarette smokers. Prescription medication and counseling have been shown to improve quit rates, yet are used by a minority of those trying to quit². Among the 68% of smokers who want to quit, less than 7% reported using counseling and only 29% reported using pharmacotherapy, and less than 5% used both³.

Cytisinicline is a plant-based, naturally-occurring investigational compound that is structurally similar to nicotine and is believed to aid in smoking cessation by binding more specifically to a certain nicotinic receptor in the brain. This binding partially stimulates dopamine release, which reduces nicotine cravings and the severity of nicotine withdrawal symptoms. It also directly inhibits nicotine binding, reducing the satisfaction typically associated with smoking.

The FDA-approved non-nicotine-containing smoking cessation therapies, varenicline, and bupropion can improve rates of smoking cessation, but they are associated with troublesome side effects. Additional treatment options are needed if we are to help more people successfully quit smoking and reduce their smoking-related health risks, While the benefits of quitting cigarette smoking are well understood in both the medical and consumer communities, it is encouraged that cigarette smokers make quitting a resolution for 2022 and to speak with their health care providers about options that can help them succeed, including potential clinical trial participation when appropriate.

ORCA-3 is being conducted to learn more about the effectiveness and safety of cytisinicline in combination with behavioral support in people trying to quit cigarette smoking. In this study, researchers want to find out if cytisinicline with behavioral support can increase the probability of abstaining from cigarette smoking. The study will also assess the safety and tolerability profile of cytisinicline.

Smoking Statistics

Despite the known health risks, cigarette smoking remains highly prevalent and difficult to quit.

• Tobacco use is currently the leading worldwide cause of preventable death
• Worldwide, over 1.1 billion people are smokers

• • Estimated that 34 million adults in US are current cigarette smokers

• For the first time in over 20 years there has been a rise in cigarette sales

• Tobacco kills up to half of its users

• • 7 million first-hand smoking deaths per year
  • 1.2 million from second-hand smoke

• The highest smoking rates are people ages 25-44 and 45-64 years old

• • Approximately 90% of all smokers start before age 18
  • Nearly 14% of adults in the US aged 18 years or older smoked cigarettes in 2018

• Other than health risks, finances are among the most motivating reasons for smokers to quit

• • On average, about 50% of current smokers smoke one pack or more in a typical day, spending ~$14 per pack of cigarettes

• Smoking-related illness in the United States costs more than $300 billion each year

• • Nearly $170 billion for direct medical care for adults
  • More than $156 billion in lost productivity

Health Risks of Smoking

Smoking is a significant risk factor for cancer, heart disease, stroke, lung diseases, diabetes, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, and reduced male and female fertility.

• Smokers are 2-4 times more likely to have coronary heart disease or stroke
• Male smokers are 25 times more likely to develop lung cancer
• Female smokers are 25.7 times more likely to develop lung cancer
• Smokers are 12-13 times more likely to die from COPD than nonsmokers

Smoking and the COVID-19 Pandemic

Centers for Disease Control and Prevention (CDC) identified smoking as a factor that may increase the risk of severe illness from COVID-19 for both current and former smokers.

Demand for New Smoking Cessation Treatments

• No new prescription (Rx) treatment options in over ten years

• • 69% of previous Rx users would be likely to try new treatment

• Adverse Effects (AEs) such as nausea/vomiting, insomnia, headaches and sleep disorders/abnormal dreams are significant barriers to complying with and completing current therapies

• • 76% do not complete the full course of treatment of the leading prescription medication for smoking cessation
  • 48% of smokers interviewed are unwilling to try currently approved treatments due to adverse events

• Nicotine addiction is on the rise due to vaping epidemic

• • 10.8M American adults use e-cigarettes
  • Teens who use e-cigarettes are 4x more likely to begin smoking tobacco cigarette

• Prescription medication and counseling combined is used by a minority of those trying to quit – of 68% of smokers who want to quit:

• • <7% reported using counseling
  • only 29% reported using pharmacotherapy
  • <5% used both counseling and pharmacotherapy.

References

[1,2] Cigarette Report for 2020 – ftc.gov. (n.d.). Retrieved November 9, 2021, from https://www.ftc.gov/system/files/documents/reports/federal-trade-commission-cigarette-report-2020-smokeless-tobacco-report-2020/p114508fy20cigarettereport.pdf.

[3] Adams AJ and Hudmon KS. Pharmacist prescriptive authority for smoking cessation medications in the United States. J Am Pharm Assoc. 2018;58(3):253-257. doi: 10.1016/j.japh.2017.12.015

 

Smoking Statistics References

• Adams AJ and Hudmon KS. Pharmacist prescriptive authority for smoking cessation medications in the United States. J Am Pharm Assoc. 2018;58(3):253-257. doi: 10.1016/j.japh.2017.12.015
• Ann Intern Med. 2018;169(7):429-438
• Centers for Disease Control and Prevention. Health Effects of Cigarette Smoking. Available at: https://www.cdc.gov/tobacco/data_statistics/fact_sheets/health_effects/effects_cig_smoking/index.htm. Updated April 28, 2020.
• Centers for Disease Control and Prevention. Coronavirus Disease 2019 (COVID-19): People with Certain Medical Conditions. Available at: https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html. Updated July 7, 2020.
• Centers for Disease Control and Prevention. Current Cigarette Smoking Among Adults in the United States. Available at: https://www.cdc.gov/tobacco/data_statistics/fact_sheets/adult_data/cig_smoking/index.htm. Updated November 18, 2019.
• Current Cigarette Smoking Among Adults in the United States. (2019, November 18). Retrieved from https://www.cdc.gov/tobacco/data_statistics/fact_sheets/adult_data/cig_smoking/index.htmHealth Effects of Cigarette Smoking. (2020, April 28). Retrieved from https://www.cdc.gov/tobacco/data_statistics/fact_sheets/health_effects/effects_cig_smoking/index.htm
• Current Cigarette Smoking Among Adults in the United States. (2019, November 18). Retrieved from https://www.cdc.gov/tobacco/data_statistics/fact_sheets/adult_data/cig_smoking/index.htm
• Data on File, Achieve Life Sciences