New treatments are needed to improve the signs and symptoms of dry eye, according to researchers who conducted the ONSET-2 phase III trial, which randomized 758 subjects 1:1:1 to placebo, 0.6 mg/mL OC-01 (Varenicline) nasal spray, or 1.2 mg/mL OC-01 (Varenicline) nasal spray twice daily for 4 weeks. Outcomes included the Schirmer Test Score (STS) at week 4 and Eye Dryness Score (EDS) at weeks 2 and 4. Both the 0.6 mg/mL and the 1.2 mg/mL doses demonstrated statistically significant increases (P<.01) in the number of patients reaching an STS of greater than or equal to 10 mm at week 4 (0.6 mg/mL, 47.3%; 1.2 mg/mL, 49.2%) compared with placebo (27.8%). Results also showed a decline in EDS (mm) from baseline for both the 0.6 mg/mL and 1.2 mg/mL doses compared with placebo at week 2 (−16.5 [P<.05], −17.9 [P =.008], and −12.7, respectively) and week 4 (−19.8 (P<.05), −22.2, and −15.4, respectively). The most common adverse event was sneezing, in 84% of patients, and the most frequent adverse events that occurred in more than 5% of patients included cough, throat irritation, and instillation site irritation.