A Second Study of Cytisinicline for Smoking Cessation in Adult Smokers (ORCA-3)

Achieve Life Sciences

Status and phase: Completed; Phase 3

Conditions: Smoking Cessation

Treatments: Behavioral: Behavioral support; Drug: Placebo; Drug: Cytisinicline

Study type: Interventional

Funder types: Industry

Identifiers

NCT05206370

ACH-CYT-04

Details and patient eligibility

About

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 and evaluate 3 mg cytisinicline TID for treatment duration of 84 days/12 weeks.

Enrollment: 792 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 all 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 during the 12-week treatment period.
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. Recent history (within 3 months) of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident, or hospitalization for congestive heart failure.
8. Current uncontrolled hypertension (blood pressure ≥160/100 mmHg).
9. Currently psychotic or having had a psychotic event within 3 months. If any subject becomes psychotic during the study, they must be removed from treatment and/or additional study visits.
10. Currently having suicidal ideation or risk for suicide ("Yes" to either question 4 or question 5 OR "Yes" to any suicidal behavior question on the Columbia Suicide Severity Rating Scale [C-SSRS] with clear suicidal intent or previous attempt).
11. Current symptoms of moderate to severe depression (depression score ≥11on the HADS).
12. Renal impairment defined as a creatinine clearance (CrCl) <60 mL/min (estimated with the Cockroft-Gault equation).
13. Hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.0 x the upper limit of normal (ULN).
14. Women who are pregnant or breast-feeding.
15. Male or female subjects of childbearing potential who do not agree to use acceptable methods of birth control during the study treatment period.
16. Participation in a clinical study with an investigational drug in the 4 weeks prior to randomization.
17. 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.
18. 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.
19. Any other reason that the investigator views the subject should not participate or would be unable to fulfill the requirements for the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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792 participants in 3 patient groups, including a placebo group

Placebo + Behavioral Support

Placebo Comparator group

Description:

One placebo tablet orally (PO) three times daily (TID) for 12 weeks plus behavioral support

Treatment:

Drug: Placebo

Behavioral: Behavioral support

6-Week Cytisinicline + 6-Week Placebo + Behavioral Support

Experimental group

Description:

One cytisinicline tablet PO TID for 6 weeks followed by one placebo tablet PO TID for 6 weeks plus behavioral support

Treatment:

Drug: Cytisinicline

Drug: Placebo

Behavioral: Behavioral support

12-Week Cytisinicline + Behavioral Support

Experimental group

Description:

One cytisinicline tablet PO TID for 12 weeks plus behavioral support

Treatment:

Drug: Cytisinicline

Behavioral: Behavioral support