A phase II randomized trial to evaluate the long-term (12-week) efficacy and safety of OC-01 (varenicline solution) nasal spray for dry eye disease: The MYSTIC study

Varenicline Solution Nasal Spray: A Review in Dry Eye Disease

“…3.1 ; Fig. 1 ); and the longer-term (12-week/84-day) MYSTIC study [ 27 ], which was conducted at a single centre in Mexico (Sect. 3.2 ).…”

“…Eligible patients were aged ≥ 22 years, had received a diagnosis of DED and had used (or expressed the desire to use) an artificial tear substitute for symptoms within 6 months of the study start [ 25 – 27 ]. The ocular inclusion criteria included: baseline Schirmer test score (STS) performed with topical anaesthesia (a measure of basal tear film production) of ≤ 10 mm/5 min and STS ≥ 7 mm greater in the same eye upon intranasal mechanical stimulation with a cotton swab; corneal fluorescein staining score of ≥ 2 in at least one corneal region or a sum of ≥ 4 for all corneal regions; OSDI score of ≥ 23, with up to three responses of “not applicable” (ONSET-1 and -2 only); and best-corrected visual acuity < 0.7 logarithm of the minimum angle of resolution [ 25 – 27 ]. If both eyes qualified, then the eye with the greatest increase in STS upon mechanical stimulation or, if no difference, the eye with the lower basal STS, was selected as the study eye [ 25 , 26 ].…”

“…Of note, eligibility in the ONSET studies was not limited by the baseline severity of DED symptoms, as assessed in terms of the eye dryness score (EDS). All three studies excluded patients who used contact lenses within 7 days of screening or anticipated using lenses during the study period [ 25 – 27 ].…”

“…Eligible patients enrolled in the phase II MYSTIC study ( n = 123) were randomized to receive varenicline solution 0.03 mg ( n = 41) or 0.06 mg ( n = 41), or vehicle ( n = 41) [ 27 ]. As in the ONSET studies, these doses of varenicline solution (and vehicle) were delivered with each actuation of an intranasal spray device; patients administered one spray (0.05 mL) in each nostril twice daily for 12 weeks.…”

Semi-PBPK Modeling and Simulation to Evaluate the Local and Systemic Pharmacokinetics of OC-01(Varenicline) Nasal Spray

“…It is hypothesized that the primary nAChR subtypes instigating the trigeminal parasympathetic pathway (TPP) are the α 4 β 2 and α 4 α 6 β 2 nAChRs located on the trigeminal nerve endings in the nasal mucosa. When delivered as a nasal spray, varenicline activates the TPP and stimulates lacrimal functional units (LFU) to promote natural tear film production, improving the signs and symptoms of DED ( Nau et al, 2021 ; Quiroz-Mercado et al, 2021 ; Wirta et al, 2021 ). To date, several clinical studies of OC-01 nasal spray have been conducted to evaluate the safety, efficacy, and pharmacokinetic (PK) of OC-01 in DED treatment ( ClinicalTrials.gov, 2021a ; ClinicalTrials.gov, 2021b ; ClinicalTrials.gov, 2021c ; ClinicalTrials.gov, 2021d ; ClinicalTrials.gov, 2021e ; ClinicalTrials.gov, 2021f ).…”