Multicenter, Randomized, Controlled, Double-Masked, Clinical Trial to Evaluate the Efficacy and Safety of OC-01 (Varenicline) Nasal Spray on Signs and Symptoms of Dry Eye Disease

Molecule Varenicline solution nasal spray (formerly known as OC-01)
Therapeutic focus Dry eye disease
Phase 3
Status Completed
Participants 758
Completion Date February 5, 2021

https://clinicaltrials.gov/study/NCT04036292.

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. Wirta D. et al.Ophthalmology. 2022;129:379–387; 2. TYRVAYA®(varenicline solution) nasal spray. Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/213978s005lbl.pdf.

Inclusion Criteria

  • A diagnosis of dry eye disease
  • ≥22 years old
  • Used and/or desired to use an artificial tear substitute for dry eye symptoms within 6 months before visit 1*​
  • Ocular Surface Disease Index (OSDI) ≥23, with ≤3 responses of “not applicable”
  • Corneal fluorescein staining (CFS) score ≥2 in at least 1 corneal region, or a sum of ≥4 for all corneal regions
  • Baseline Schirmer’s test score (STS) (using topical anesthesia with proparacaine) of ≤10 mm/5 minutes, with a cotton swab nasal stimulation STS of ≥7 mm more in the same eye​
  • <20-mm difference between the study and fellow eye STS
  • Best-corrected visual acuity (BCVA) of 0.7 logarithm of the minimum angle of resolution or better (Snellen equivalent, 20/100 or better) in each eye
  • Normal lid and lash anatomic features†, blinking function, and closure
Eligibility was not restricted by eye dryness score (EDS). *Artificial tear use during the clinical trial was permitted.†Patients with mild meibomian gland disease typically associated with dry eye disease were included.
Wirta D. et al.Ophthalmology. 2022;129:379–387.

Exclusion Criteria

  • Significant corneal epithelial defects
  • Chronic or recurrent epistaxis, coagulation disorders, or other conditions that may lead to a clinically significant increased risk of bleeding
  • Nasal or sinus surgery
  • Vascularized polyp, severely deviated septum, chronic recurrent nosebleeds, or severe nasal obstruction
  • Current use of nasal continuous positive airway pressure (CPAP) therapy
  • Any intraocular surgery, extraocular surgery in either eye within 3 months or refractive surgery within 12 months
  • Blepharoplasty or corneal transplant in either eye
  • Contact lens use within 7 days before the study or anticipated use during the study
  • Any form of punctal or intracanalicular occlusion
  • History or presence of any ocular disorder that would likely interfere with patient safety or data interpretation
  • A history of seizures
  • Concomitant use of a nicotinic acetylcholine receptor (nAChR) agonist within the previous 30 days
Patients with an autoimmune disease were not excluded.
Wirta D. et al.Ophthalmology. 2022;129:379–387.

Primary Endpoint

  • Percentage of patients who achieved a ≥10-mm improvement in Schirmer’s test score (STS) in the study eye from baseline to day 28
Wirta D. et al.Ophthalmology. 2022;129:379–387.

Secondary Endpoints

  • Mean change in eye dryness score (EDS) (5 minutes post-treatment)*from baseline to day 28 in the controlled adverse environment (CAE®)1,2
  • Mean change in EDS from baseline to day 28*in the clinic1,2
  • Mean change in Schirmer’s test score (STS) from baseline to day 282
  • Mean change in EDS at day 142
  • Mean change in EDS at day 72
  • Change in corneal fluorescein staining (CFS) from baseline to day 28†,1
CAE®is a registered trademark of Ora, Inc. *On a 100-mm visual analog scale from 0 (no discomfort) to 100 (maximal discomfort)1,2 †Performed after assessment of STS with anesthesia at day 28 and graded based on the National Eye Institute/Industry Workshop Scale, using a standardized grading system of 0 to 3 to assess each of the 5 corneal regions (central, superior, inferior, nasal, and temporal), followed by calculation of the total score for all regions.1
1. Wirta D. et al.Ophthalmology. 2022;129:379–387; 2. https://clinicaltrials.gov/study/NCT04036292.

Safety Endpoints

  • Treatment emergent adverse events (TEAEs)*
  • Intranasal examination
  • Slit lamp biomicroscopy
  • Best-corrected visual acuity (BCVA) assessment
  • Sneezing, as collected by diary
*Defined as adverse events that were new or had worsened in severity since the first study drug use.
Wirta D. et al.Ophthalmology. 2022;129:379–387.

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;†Oyster Point Pharma, Inc. Data on file.
EDS, eye dryness score; FDA, Food and Drug Administration; SD, standard deviation; STS, Schirmer's test score; VNS, varenicline solution nasal spray​.
1. Wirta D. et al.Ophthalmology. 2022;129:379–387; 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 ITT population. Cochran-Mantel-Haenszel test controlling for study site, baseline STS, and baseline EDS. All comparisons made with the control group.1
EDS, eye dryness score; FDA, Food and Drug Administration; ITT, intention-to-treat; STS, Schirmer's test score; VNS, varenicline solution nasal spray.
1. Wirta D. et al.Ophthalmology. 2022;129:379–387; 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.2 ITT population. Pairwise treatment group differences were compared using ANCOVA models with treatment group, study site, baseline STS, and baseline EDS as covariates. All comparisons made with the control group. Nominalp-values.1 *Oyster Point Pharma, Inc. Data on file.
ANCOVA, analysis of covariance; CI, confidence interval; EDS, eye dryness score; FDA, Food and Drug Administration; ITT, intention-to-treat; LS, least squares; STS, Schirmer's test score; VNS, varenicline solution nasal spray​.
1. Wirta D. et al.Ophthalmology. 2022;129:379–387; 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.2 Modified ITT population (excluded 2 sites because of their inability to collect specific study data due to the coronavirus disease 2019 pandemic). Pairwise treatment group differences were compared using ANCOVA models with treatment group, study site, baseline STS, and baseline EDS as covariates. All comparisons made with the control group. Nominal p-values.1 *Oyster Point Pharma, Inc. Data on file.ANCOVA, analysis of covariance; CAE®, controlled adverse environment; CI, confidence interval; EDS, eye dryness score; FDA, Food and Drug Administration; ITT, intention-to-treat; LS, least squares; STS, Schirmer's test score; VNS, varenicline solution nasal spray​.
1. Wirta D. et al.Ophthalmology. 2022;129:379–387; 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.2 ITT population. Pairwise treatment group differences were compared using ANCOVA models with treatment group, study site, baseline STS, and baseline EDS as covariates. All comparisons made with the control group. Nominalp-values due to closed hierarchical testing procedure.1*Oyster Point Pharma, Inc. Data on file.
ANCOVA, analysis of covariance; CI, confidence interval; EDS, eye dryness score; FDA, Food and Drug Administration; ITT, intention-to-treat; LS, least squares; NS, not significant; STS, Schirmer's test score; VNS, varenicline solution nasal spray​.
1. Wirta D. et al.Ophthalmology. 2022;129:379–387; 2. TYRVAYA®(varenicline solution) nasal spray. Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/213978s005lbl.pdf.

Safety Outcome Measures1

Note: The FDA-approved dosage of varenicline solution nasal spray is 0.03 mg BID.2 *Data presented as n (%). No clinically significant findings for intranasal examination, slitlamp biomicroscopy, or BCVA assessment. 3 deaths occurred during the study (during the post-treatment follow-up period) as a result of adverse events not considered related to the study drug (pneumonia, cerebrovascular accident, coronavirus infection). No patients reported serious TEAEs considered to be related to the study drug; †The most commonly reported ocular TEAEs. Most of these events were not considered related to the study drug; ‡The most commonly reported nonocular TEAEs. Most events were considered mild. The incidences of all other nonocular TEAEs were similar across treatment groups.
BCVA, best-corrected visual acuity; FDA, Food and Drug Administration; TEAE, treatment-emergent adverse event; VNS, varenicline solution nasal spray​.
1. Wirta D. et al.Ophthalmology. 2022;129:379–387; 2. TYRVAYA®(varenicline solution) nasal spray. Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/213978s005lbl.pdf.

Safety Outcome Measures

Categories for number of sneezes after study drug delivery: 0 (no sneezes), 1.5 (1–2 sneezes), 4 (3–5 sneezes), and 7 (≥6 sneezes).
Oyster Point Pharma, Inc. Data on file.
VNS, varenicline solution nasal spray.