A phase 3 randomized, double-blind, placebo-controlled trial evaluated the efficacy and safety of cytisinicline, a plant-derived partial agonist at α4β2 nicotinic acetylcholine receptors, for smoking cessation in adults who smoked at least 10 cigarettes per day.

The trial enrolled 792 participants at 20 sites across the U.S. between January 2022 and March 2023. Participants were randomly assigned to cytisinicline 3 mg orally three times daily for 12 weeks, cytisinicline 3 mg orally three times daily for 6 weeks followed by placebo, or placebo for 12 weeks. All participants received up to 14 behavioral counseling sessions and were followed through week 24.

The primary outcome was continuous abstinence during the final 4 weeks of treatment, confirmed by expired carbon monoxide less than 10 ppm. In the 12-week cytisinicline group, 30.3% were abstinent during weeks 9 through 12 vs 9.4% with placebo. In the 6-week group, 14.8% were abstinent during weeks 3 through 6 vs 6.0% with placebo.

Cytisinicline also improved continuous abstinence through week 24. Among participants receiving cytisinicline for 12 weeks, 20.5% remained abstinent from weeks 9 through 24 compared with 4.2% in the placebo group. In the 6-week group, 6.8% remained abstinent from weeks 3 through 24 vs 1.1% with placebo.

Cytisinicline was associated with greater reductions in craving, as measured by the Brief Questionnaire of Smoking Urges. By week 6, craving scores declined by 15.2 points in the cytisinicline group vs 12.0 points in the placebo group. Both reward-related (QSU-1) and withdrawal-related (QSU-2) subscale scores improved with cytisinicline.

Among participants who did not achieve abstinence, those receiving cytisinicline had greater reductions in serum cotinine levels. In the 6-week cytisinicline group, the mean cotinine reduction at week 6 was –150.21 ng/mL vs. –38.26 ng/mL with placebo.

Adherence to treatment was high, with more than 75% of participants completing the full medication course. Treatment-emergent adverse events occurred at similar rates across groups. The most common adverse events were insomnia, abnormal dreams, nausea, and headache. Serious adverse events occurred in 3.1% of participants in both the cytisinicline and placebo groups; none were attributed to cytisinicline.

These findings support the efficacy and safety of cytisinicline as a pharmacologic aid for smoking cessation.

Full disclosures are available in the original study.

Source: JAMA Internal Medicine