A Study of Cytisinicline for Smoking Cessation in Adult Smokers (ORCA-2)

• ClinicalTrials.gov Identifier: NCT04576949
• Recruitment Status: Completed
• First Posted: October 6, 2020
• Last Update Posted: December 6, 2022
• Sponsor: Achieve Life Sciences
• Information provided by (Responsible Party): Achieve Life Sciences

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Smoking Cessation	Drug: Cytisinicline; Drug: Placebo; Behavioral: Behavioral support	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 810 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Double-blind, Randomized, Placebo-controlled Phase 3 Trial Evaluating the Efficacy and Safety of Cytisinicline in Adult Smokers
• Actual Study Start Date: October 13, 2020
• Actual Primary Completion Date: December 23, 2021
• Actual Study Completion Date: December 23, 2021

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Placebo + Behavioral Support; one placebo tablet orally (PO) three times daily (TID) plus behavioral support for 12 weeks	Drug: 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.
Experimental: Cytisinicline + Placebo + Behavioral Support; one cytisinicline tablet PO TID plus behavioral support for 6 weeks followed by one placebo tablet PO TID plus behavioral support for 6 weeks	Drug: Cytisinicline; film-coated oral tablets containing 3 mg cytisinicline; Other Name: Cytisine; Drug: 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.
Experimental: Cytisinicline + Behavioral Support; one cytisinicline tablet PO TID plus behavioral support for 12 weeks	Drug: Cytisinicline; film-coated oral tablets containing 3 mg cytisinicline; Other Name: Cytisine; 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.

Outcome Measures

Primary Outcome Measures :

1. Proportion of participants with smoking abstinence during the last 4 weeks of 6 weeks cytisinicline treatment versus placebo treatment (Wk 3-6) [ Time Frame: Week 3-6 ]
   Smoking abstinence as verified by weekly expired carbon monoxide (CO) measurements ≤10 parts per million (ppm).
2. Proportion of participants with smoking abstinence during the last 4 weeks of 12 weeks cytisinicline treatment versus placebo treatment (Wk 9-12) [ Time Frame: Week 9-12 ]
   Smoking abstinence as verified by weekly expired carbon monoxide (CO) measurements ≤10 parts per million (ppm).

Secondary Outcome Measures :

1. Proportion of participants with continuous smoking abstinence to Week 24 [ Time Frame: Week 24 ]
   Smoking abstinence as verified by monthly expired CO measurements ≤10 ppm.
2. Proportion of Participants Who are Relapse-Free at Week 24 [ Time Frame: Week 24 ]
   Relapse is defined as participant reported resuming smoking or an expired CO measure ≥ 10ppm

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Alabama

Alliance for Multispecialty Research, LLC.

Mobile, Alabama, United States, 36608

United States, Arizona

Arizona State University

Phoenix, Arizona, United States, 85044

United States, Florida

Alliance for Multispecialty Research, LLC

Coral Gables, Florida, United States, 33134

United States, Georgia

Clinical Research Atlanta

Atlanta, Georgia, United States, 30281

United States, Indiana

MediSphere Medical Research Center, LLC

Evansville, Indiana, United States, 47714

United States, Kansas

Alliance for Multispecialty Research, LLC

Wichita, Kansas, United States, 67207

United States, Kentucky

AMR Lexington

Lexington, Kentucky, United States, 40509

United States, Louisiana

Alliance for Multispecialty Research, LLC

New Orleans, Louisiana, United States, 70119

United States, Massachusetts

Massachusetts General Hospital - Clinical Genetic Research Facility

Boston, Massachusetts, United States, 02114

United States, Missouri

Alliance for Multispecialty Research, LLC

Kansas City, Missouri, United States, 64114

United States, Nevada

Alliance for Multispecialty Research, LLC

Las Vegas, Nevada, United States, 89119

United States, New York

Rochester Clinical Research, Inc.

Rochester, New York, United States, 14609

United States, North Carolina

M3 Wake Research, Inc.

Raleigh, North Carolina, United States, 27612

United States, South Carolina

Coastal Carolina Research Center, Inc.

Mount Pleasant, South Carolina, United States, 29464

United States, Tennessee

Alliance for Multispecialty Research, LLC.

Knoxville, Tennessee, United States, 37920

United States, Texas

FutureSearch Trials of Dallas, LP

Dallas, Texas, United States, 75231

United States, Virginia

Alliance for Multispecialty Research, LLC

Norfolk, Virginia, United States, 23502

Sponsors and Collaborators

Achieve Life Sciences

Investigators

• Principal Investigator: Nancy Rigotti, MD; Mass General/Harvard Medical School

More Information

• Responsible Party: Achieve Life Sciences
• ClinicalTrials.gov Identifier: NCT04576949
• Other Study ID Numbers: ACH-CYT-03
• First Posted: October 6, 2020
• Last Update Posted: December 6, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No