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.