• Cornea/External Disease

    In a phase 2 vehicle-controlled study, 0.03 mg and 0.06 mg dosages of varenicline for patients with dry eye showed statistically significant greater improvements in tear film production, through a mode of nasal drug delivery.

    Study design

    This was a phase 2b, multicenter, randomized, double-masked, vehicle-controlled trial that evaluated the safety and efficacy of OC-01 NS (varenicline solution) on the signs and symptoms of dry eye. One hundred eighty-two patients 22 years or older treated previously only with artificial tears were randomized 1:1:1:1: to control nasal spray 2 times a day, OC-01 0.006 mg two times daily, OC-01 0.03 mg two times daily, and OC-01 0.06 mg two times daily. Primary endpoint was change in anesthetized Schirmer test score from baseline to day 28. Secondary endpoints were change in eye dryness score (EDS) from baseline to day 28 and change in eye dryness score from baseline to day 21 five minutes post-treatment within a controlled adverse environment compared with those patients treated with vehicle.

    Outcomes

    Patients who received OC-01 0.03 mg and 0.06 mg dosages showed statistically significant greater improvements in tear film production compared to vehicle. Both concentrations increased Schirmer test scores from ~5.0 mm at baseline to ~16.0 mm within 28 days. Patients who received the OC-01 0.03 mg dose showed a statistically significant greater mean reduction in EDS from baseline to day 28 compared with those who received vehicle. Patients who received the OC-01 0.03 or 0.06 mg dose showed statistically significant greater mean reductions in EDS from baseline to day 21 (5 minutes posttreatment) within the controlled adverse environment compared with those patients treated with vehicle.

    Limitations

    OC-01 nasal spray was associated with adverse events such as sneezing and coughing, but these occurred only transiently. One limitation of this study was that tear production was only assessed at the time of OC-01 administration, but the duration of increased tear production after treatment was not assessed.

    Clinical significance

    OC-01 (varenicline solution) is a preservative-free, highly selective nicotinic acetylcholine receptor (nAChR) agonist nasal spray that activates the trigeminal parasympathetic pathway, upregulates natural tear production, and shows great promise in treating the signs and symptoms of dry eye disease when compared to a control vehicle. It offers an alternative mode of nasal drug delivery for dry eye patients who already experience high eyedrop burden and utilizes a novel method for tear stimulation by activating the trigeminal parasympathetic pathway and bypassing the afferent pathways of the cornea and conjunctiva.