A Study of Cytisinicline for Smoking Cessation in Adult Smokers

Smoking Cessation Clinical Trial

— ORCA-2  

Official title:

A Multicenter, Double-blind, Randomized, Placebo-controlled Phase 3 Trial Evaluating the Efficacy and Safety of Cytisinicline in Adult Smokers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04576949
• Other study ID #: ACH-CYT-03
• Status: Completed
• Phase: Phase 3
• Start date: October 13, 2020
• Est. completion date: December 23, 2021

Study information

• Verified date: December 2022
• Source: Achieve Life Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This placebo-controlled Phase 3 study is being conducted at sites within the United States to evaluate 3 mg cytisinicline TID for treatment duration of 42 days/6 weeks as well as repeating that duration for a total of 84 days/12 weeks treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 810
• Est. completion date: December 23, 2021
• Est. primary completion date: December 23, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Male or female subjects, age =18 years.

2. Current daily cigarette smokers (averaging at least 10 cigarettes per day upon completing a 7-day screening smoking diary) and who intend to quit smoking.

3. Expired air carbon monoxide (CO) =10 ppm.

4. Failed at least one previous attempt to stop smoking with or without therapeutic support.

5. Willing to initiate study treatment on the day after randomization and set a quit date within 5-7 days of starting treatment.

6. Willing to actively participate in the study's smoking cessation behavioral support provided throughout the study.

7. Able to fully understand study requirements, willing to participate, and comply with dosing schedule.

8. Sign the Informed Consent Form.

Exclusion Criteria:

1. More than 1 study participant in same household.

2. Previous cytisinicline treatment in a prior clinical study or any other cytisine usage.

3. Known hypersensitivity to cytisinicline or any of the excipients.

4. Positive urinary drugs of abuse screen, determined within 28 days before the first dose of cytisinicline.

5. Clinically significant abnormal serum chemistry or hematology values within 28 days of randomization (ie, requiring treatment or monitoring).

6. Clinically significant abnormalities in 12-lead ECG determined after minimum of 5 minutes in supine position within 28 days of randomization (ie, requiring treatment or further assessment).

7. BMI classification for being underweight (<18.5 kg/m2) or having =Class 2 obesity (=35 kg/m2).

8. Recent history (within 3 months) of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident or hospitalization for congestive heart failure.

9. Current uncontrolled hypertension (blood pressure =160/100 mmHg).

10. Documented diagnosis of schizophrenia or bipolar psychiatric illness; currently psychotic.

11. Currently having suicidal ideation or risk for suicide ("Yes" to question 4 or question 5 OR "Yes" to any suicidal behavior question on the C-SSRS).

12. Current symptoms of moderate to severe depression (HADS score =11).

13. Renal impairment defined as a creatinine clearance (CrCl) <60 mL/min (estimated with the Cockroft-Gault equation).

14. Hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.0 x the upper limit of normal (ULN).

15. Women who are pregnant or breast-feeding.

16. Male or female subjects of childbearing potential who do not agree to use acceptable methods of birth control during the study treatment period.

17. Participation in a clinical study with an investigational drug in the 4 weeks prior to randomization.

18. Treatment with other smoking cessation medications (bupropion, varenicline, nortriptyline, or any nicotine replacement therapy [NRT]) in the 4 weeks prior to randomization or planned use of these other smoking cessation medications during the study.

19. Use within the 2 weeks prior to randomization or planned use during the study of non-cigarette and/or noncombustible nicotine products (pipe tobacco, cigars, snuff, smokeless tobacco, hookah, e-cigarettes/vaping) or marijuana smoking or vaping.

20. Any other reason that the investigator views the subject should not participate or would be unable to fulfill the requirements for the study.

Related Conditions & MeSH terms

• Smoking Cessation

Intervention

Drug:
• Cytisinicline
film-coated oral tablets containing 3 mg cytisinicline
• Placebo
film-coated oral tablets containing matched placebo

Behavioral:
• Behavioral support
Behavioral support sessions by a qualified study site staff member will be participant-driven and will include direct engagement with the subject about their attempt to quit smoking. Each session will last approximately 10 minutes.

Locations

Country	Name	City	State
United States	Clinical Research Atlanta	Atlanta	Georgia
United States	Massachusetts General Hospital - Clinical Genetic Research Facility	Boston	Massachusetts
United States	Alliance for Multispecialty Research, LLC	Coral Gables	Florida
United States	FutureSearch Trials of Dallas, LP	Dallas	Texas
United States	MediSphere Medical Research Center, LLC	Evansville	Indiana
United States	Alliance for Multispecialty Research, LLC	Kansas City	Missouri
United States	Alliance for Multispecialty Research, LLC.	Knoxville	Tennessee
United States	Alliance for Multispecialty Research, LLC	Las Vegas	Nevada
United States	AMR Lexington	Lexington	Kentucky
United States	Alliance for Multispecialty Research, LLC.	Mobile	Alabama
United States	Coastal Carolina Research Center, Inc.	Mount Pleasant	South Carolina
United States	Alliance for Multispecialty Research, LLC	New Orleans	Louisiana
United States	Alliance for Multispecialty Research, LLC	Norfolk	Virginia
United States	Arizona State University	Phoenix	Arizona
United States	M3 Wake Research, Inc.	Raleigh	North Carolina
United States	Rochester Clinical Research, Inc.	Rochester	New York
United States	Alliance for Multispecialty Research, LLC	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Achieve Life Sciences

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of participants with smoking abstinence during the last 4 weeks of 6 weeks cytisinicline treatment versus placebo treatment (Wk 3-6)	Smoking abstinence as verified by weekly expired carbon monoxide (CO) measurements =10 parts per million (ppm).	Week 3-6
Primary	Proportion of participants with smoking abstinence during the last 4 weeks of 12 weeks cytisinicline treatment versus placebo treatment (Wk 9-12)	Smoking abstinence as verified by weekly expired carbon monoxide (CO) measurements =10 parts per million (ppm).	Week 9-12
Secondary	Proportion of participants with continuous smoking abstinence to Week 24	Smoking abstinence as verified by monthly expired CO measurements =10 ppm.	Week 24
Secondary	Proportion of Participants Who are Relapse-Free at Week 24	Relapse is defined as participant reported resuming smoking or an expired CO measure = 10ppm	Week 24