Randomized, Controlled, Single-Masked Clinical Trial to Evaluate the Chronic Efficacy of OC-01 Nasal Spray on Signs of Dry Eye Disease

Molecule Varenicline solution nasal spray (formerly known as OC-01)
Therapeutic focus Dry eye disease
Phase 2
Status Completed
Participants 123
Completion Date January 7, 2020

Note: Single-site study. All subjects were Hispanic or Latino.
https://clinicaltrials.gov/study/NCT03873246.

Trial Design1

Note: The FDA-approved dosage of varenicline solution nasal spray is 0.03 mg BID.2
BID, twice daily; FDA, Food and Drug Administration.
1. Quiroz-Mercado H. et al.Ocul Surf. 2022;24:15–21; 2. TYRVAYA®(varenicline solution) nasal spray. Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/213978s005lbl.pdf.

Inclusion Criteria

  • ≥22 years old
  • A diagnosis of dry eye disease
  • Used or desired to use an artificial tear substitute for dry eye symptoms within 6 months of screening*
  • All of the following in the study eye at screening:​
    • Corneal fluorescein staining (CFS) score of ≥2 in >1 corneal region, or a sum of ≥4 for all corneal regions​
    • Baseline Schirmer’s test score (STS) of ≤10 mm/5 minutes, with a cotton swab nasal stimulation STS of ≥7 mm more in the same eye
    • Best-corrected visual acuity (BCVA) of ≤0.7 logarithm of the minimum angle of resolution
*Artificial tear use during the clinical trial was permitted.
Quiroz-Mercado H. et al.Ocul Surf. 2022;24:15–21.

Exclusion Criteria

  • Chronic or recurrent epistaxis, coagulation disorders, or other conditions that may lead to a clinically significant risk of increased bleeding
  • Active or uncontrolled severe systemic allergy, chronic seasonal allergies, rhinitis, or sinusitis requiring treatment
  • Untreated nasal infection
  • Previous nasal or sinus surgery
  • Major traumatic nasal or sinus injuries
  • Vascularized polyps, severely deviated septum, chronic recurrent nosebleeds, or severe nasal airway obstruction
  • Current use of nasal CPAP therapy
  • Clinically significant corneal epithelial defects (as judged by the investigator)
  • Intraocular or extraocular surgery within 3 months or refractive surgery within 12 months of screening
  • Corneal transplant
  • Contact lens use within 7 days before screening or anticipated use during the study
  • Any form of punctal or intracanalicular occlusion
  • History or presence of an ocular disorder/condition that would interfere with patient safety or data interpretation*
  • Current, or within the previous 30 days, concomitant use of an nAChR agonist (nicotine, cytisine, varenicline)
  • Hypersensitivity to any of the procedural agents or study drug components
  • Pregnancy
*Blepharitis not requiring treatment and/or mild meibomian gland disease was allowed.
CPAP, continuous positive airway pressure; nAChR, nicotinic acetylcholine receptor.
Quiroz-Mercado H. et al.Ocul Surf. 2022;24:15–21.

Primary Endpoint

  • Mean change in anesthetized Schirmer’s test score (STS) in the study eye from baseline to day 84
Quiroz-Mercado H. et al.Ocul Surf. 2022;24:15–21.

Other Efficacy Endpoints

  • Percentage of subjects who achieve:
    • A ≥10-mm improvement in Schirmer’s test score (STS) from baseline to day 841,2
    • A ≥10-mm improvement in STS from baseline to day 281
  • Mean change in STS in:
    • The fellow eye from baseline to day 841
    • The study eye from baseline to day 281
    • The fellow eye from baseline to day 281
  • Mean change in total corneal fluorescein staining (CFS) from baseline to day 56*,1
Graded using a standardized grading system of 0 to 3 to assess each of the 5 corneal regions (central, superior, inferior, nasal, and temporal).1
1. https://clinicaltrials.gov/study/NCT03873246; 2. Quiroz-Mercado H. et al.Ocul Surf. 2022;24:15–21.

Safety Endpoints

  • Treatment emergent adverse events (TEAEs)
  • Slit lamp biomicroscopy
  • Best-corrected visual acuity (BCVA) assessment
  • Intranasal examination
  • Pupil diameter
All adverse events were coded using the Medical Dictionary for Regulatory Activities, version 20.1. The event severity was defined as a qualitative assessment of its degree of intensity, as determined by the investigator or reported by the patient. Adverse events were categorized as ocular and nonocular, as well as by System Organ Class and Preferred Term, seriousness, severity, and relation to study drug. TEAEs were summarized by patient level.
Quiroz-Mercado H. et al.Ocul Surf. 2022;24:15–21.

Baseline Characteristics1

Note: The FDA-approved dosage of varenicline solution nasal spray is 0.03 mg BID.2 *Data presented as mean (SD), unless otherwise specified.
FDA, Food and Drug Administration; SD, standard deviation; STS, Schirmer's test score; VNS, varenicline solution nasal spray.
1. Quiroz-Mercado H. et al.Ocul Surf. 2022;24:15–21; 2. TYRVAYA®(varenicline solution) nasal spray. Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/213978s005lbl.pdf.

Efficacy Outcome Measures – Primary Endpoint1

Note: The FDA-approved dosage of varenicline solution nasal spray is 0.03 mg BID.2 Analyzed using an ANCOVA model with baseline STS and treatment group as covariates. All comparisons made with the control group.1 *Oyster Point Pharma, Inc. Data on file.
ANCOVA, analysis of covariance; CI, confidence interval; FDA, Food and Drug Administration; LS, least squares; STS, Schirmer's test score; VNS, varenicline solution nasal spray​.
1. Quiroz-Mercado H. et al.Ocul Surf. 2022;24:15–21; 2. TYRVAYA®(varenicline solution) nasal spray. Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/213978s005lbl.pdf.

Efficacy Outcome Measures – Secondary Endpoint1

Note: The FDA-approved dosage of varenicline solution nasal spray is 0.03 mg BID.3 Analyzed using an ANCOVA model with baseline STS and treatment group as covariates. All comparisons made with the control group.2 VNS 0.03 mg group mean baseline STS 5.5 mm (n=41); VNS 0.06 mg group mean baseline STS 5.4 mm (n=41); control group mean baseline STS 5.3 mm (n=41).1 All randomized and treated patients were included in the analysis and missing data were imputed using last-available data.1,2
ANCOVA, analysis of covariance; FDA, Food and Drug Administration; STS, Schirmer's test score; VNS, varenicline solution nasal spray​.
1. MYSTIC Oyster Point Pharma, Inc. Data on file; 2. Quiroz-Mercado H. et al.Ocul Surf. 2022;24:15–21; 3. TYRVAYA®(varenicline solution) nasal spray. Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/213978s005lbl.pdf.

Safety Outcome Measures*1

Note: The FDA-approved dosage of varenicline solution nasal spray is 0.03 mg BID.3 *Data presented as n (%). TEAEs >5% are reported. No clinically relevant changes from baseline in BCVA, slitlamp biomicroscopy findings, pupil diameter, or intranasal examinations were observed. No deaths were reported; †Depression on day 30. Nausea, dizziness, and nasal discomfort on day 1. Chest pain and dyspnea on day 1; ‡Headache on day 1; §Nausea on day 1. Headache on day 13; eye irritation and headache on day 1.
BCVA, best-corrected visual acuity; FDA, Food and Drug Administration; TEAE, treatment-emergent adverse event; VNS, varenicline solution nasal spray​.
1. Quiroz-Mercado H. et al.Ocul Surf. 2022;24:15–21; 2. TYRVAYA®(varenicline solution) nasal spray. Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/213978s005lbl.pdf.