À¶Ý®ÊÓƵ

Skip to main content
 
Notice: Users may be experiencing issues with displaying some pages on stanfordhealthcare.org. We are working closely with our technical teams to resolve the issue as quickly as possible. Thank you for your patience.
À¶Ý®ÊÓƵ

Cytisinicline for Smoking Cessation: The ORCA Phase 3 Replication Randomized Clinical Trial.

À¶Ý®ÊÓƵ

Cytisinicline for Smoking Cessation: The ORCA Phase 3 Replication Randomized Clinical Trial. JAMA internal medicine Rigotti, N. A., Benowitz, N. L., Prochaska, J. J., Rubinstein, M., Clarke, A., Blumenstein, B., Cain, D. F., Jacobs, C. 2025

Abstract

New smoking cessation medication options are needed. Cytisinicline, a partial agonist at a4ß2 nicotinic acetylcholine receptors, has demonstrated smoking cessation efficacy in 1 US trial. Additional evidence is needed.To reproduce the findings of the efficacy and tolerability of cytisinicline compared with placebo for smoking cessation and to test its effect on nicotine craving as a mechanism of action.This was a 3-group double-blind, placebo-controlled phase 3 replication randomized clinical trial (ORCA-3) conducted at 20 clinical trial sites in the US from January 2022 to March 2023. It compared 6 and 12 weeks of a novel cytisinicline regimen to placebo among adults who smoked 10 or more cigarettes daily and sought to quit. Participants were randomized (1:1:1) to 3-mg cytisinicline 3 times daily for 12 weeks; 3-mg cytisinicline 3 times daily for 6 weeks followed by placebo for 6 weeks; or placebo 3 times daily for 12 weeks. The follow-up period was 24 weeks, and all groups received behavioral support. Data analyses were performed from May 3, 2023, to March 20, 2024.Cytisinicline, 3 mg, 3 times daily for 12 weeks; cytisinicline, 3 mg, 3 times daily for 6 weeks followed by placebo for 6 weeks; or placebo 3 times daily for 12 weeks.Biochemically verified (carbon monoxide <10 ppm) continuous smoking abstinence during the last 4 weeks of 6- and 12-week treatments (primary outcome) and from end of treatment to 24 weeks (secondary outcome); Questionnaire of Smoking Urges; incidence of adverse events.Of 792 participants randomized (mean [SD] age, 52.0 [11.8] years; 439 [55.4%] female; mean [SD] cigarettes/d, 20.4 [7.5]), 628 (79.3%) completed the trial. Primary and secondary outcomes were significantly higher for both cytisinicline groups vs placebo. For 6-week treatment, 39 cytisinicline participants (14.8%) vs 16 placebo participants (6.0%) were abstinent during weeks 3 to 6 (odds ratio [OR], 2.9; 95% CI, 1.5-5.6; P?

View details for

View details for