Multicenter, Randomized, Controlled, Double-Masked Clinical Trial to Evaluate the Efficacy of OC-01 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 2b
Status Completed
Participants 182
Completion Date September 26, 2018

https://clinicaltrials.gov/study/NCT03636061.

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.Cornea. 2022;41:1207–1216; 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 at screening
  • A physician’s diagnosis of dry eye disease​
  • Used and/or desired to use artificial tears for dry eye symptoms within 6 months of study start*
  • Ocular Surface Disease Index (OSDI) ≥23 at screening with ≤3 responses of “not applicable”
  • All of the following in the study eye at screening:​
    • Corneal fluorescein staining (CFS) score of ≥2 in at least 1 corneal region, or a sum of ≥4 for all corneal regions​
    • Baseline Schirmer’s test score (STS) (with topical anesthesia) of ≤10 mm/5 minutes
    • STS ≥7 mm larger in the same eye​ after bilateral intranasal cotton swab stimulation
  • Best-corrected visual acuity (BCVA) <0.7 logarithm of the minimum angle of resolution in each eye
*Artificial tear use during the clinical trial was permitted.
Wirta D. et al. Cornea. 2022;41:1207–1216.

Exclusion Criteria

  • Chronic or recurrent epistaxis, coagulation disorders, or other conditions that may lead to a clinically significant risk of increased bleeding1
  • A history of seizures1
  • Current use of nasal continuous positive airway pressure (CPAP) therapy1
  • Nasal or sinus surgery or significant trauma to these areas1
  • A corneal transplant1
  • Contact lens use within 7 days of the first visit or anticipated use during the study1
  • Any form of punctal or intracanalicular occlusion1
  • Any systemic, ocular, or nasal disease or any condition that would interfere with patient safety or data interpretation1
  • Use of snuff, chewing tobacco, e-cigarettes, or cigarettes/cigars within 30 days of or during the study1
  • Use of nicotinic acetylcholine receptor (nAChR) agonists (nicotine/cytisine/varenicline) within 30 days of the study1
  • An ongoing ocular condition (e.g. infection or clinically significant corneal condition)*,1
  • Previous intraocular surgery (such as cataract surgery) or extraocular surgery (such as blepharoplasty) in either eye within 3 months or refractive surgery within 12 months of baseline2
*Blepharitis not requiring treatment and/or mild meibomian gland disease was allowed.
1. Wirta D. et al. Cornea. 2022;41:1207–1216; 2. https://clinicaltrials.gov/study/NCT03636061.

Primary Endpoint

  • Change in anesthetized Schirmer’s test score (STS) from baseline to day 28 in the study eye
Wirta D. et al. Cornea. 2022;41:1207–1216. .

Key Secondary Endpoints

  • Change in eye dryness score (EDS) from baseline to day 28*
  • Change in EDS from baseline to day 21 (5 minutes post-treatment)* in the controlled adverse environment (CAE®)
CAE®is a registered trademark of Ora, Inc. *On a 100-mm visual analog scale from 0 (no discomfort) to 100 (maximal discomfort).
Wirta D. et al. Cornea. 2022;41:1207–1216.

Safety Endpoints

  • Treatment emergent adverse events (TEAEs)*
  • Change in best-corrected visual acuity (BCVA)
  • Slit lamp biomicroscopy findings
  • Intranasal examination†
*The investigator graded TEAE severity as mild, moderate, or severe and recorded the relationship to the study drug as definite, probable, possible, not related, or unclassified. The investigator defined expectedness (i.e. expected, unexpected, or not applicable) using existing safety information about the study drug. A TEAE was considered to be a serious adverse event (SAE) if it was life-threatening, resulted in hospitalization admission or prolonged an existing hospitalization, caused a persistent or significant incapacity or substantial disruption in the ability to conduct normal life functions, caused a congenital anomaly or birth defect, or resulted in death;†Performed at the screening visit and at day 28 or on early termination.
Wirta D. et al. Cornea. 2022;41:1207–1216.

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;†Includes American Indian or Alaska Native, and Native Hawaiian or other Pacific Islander;‡Assessment relates to both eyes.
EDS, eye dryness score; FDA, Food and Drug Administration; OSDI, Ocular Surface Disease Index; SD, standard deviation; STS, Schirmer’s test score; VNS, varenicline solution nasal spray​.
1. Wirta D. et al. Cornea. 2022;41:1207–1216; 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

Mean change in STS in the study eye from baseline to day 28

Note: The FDA-approved dosage of varenicline solution nasal spray is 0.03 mg BID.2 LS means were derived from ANCOVA model with treatment, site, baseline STS, and STS with a cotton swab stimulation as covariates.3 The results are derived from a posthoc analysis. LOCF imputation method is used.1,3 All comparisons made with the control group. No formal statistical comparisons were performed for the 0.006 mg dose versus control.3
ANCOVA, analysis of covariance; CI, confidence interval; FDA, Food and Drug Administration; LOCF; last observation carried forward; LS, least squares; STS, Schirmer’s test score; VNS, varenicline solution nasal spray.
1. ONSET-1 Oyster Point Pharma, Inc. Data on file; 2. TYRVAYA® (varenicline solution) nasal spray. Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/213978s005lbl.pdf; 3. Wirta D. et al. Cornea. 2022;41:1207–1216.

Efficacy Outcome Measures – Exploratory Endpoint1

Percentage of subjects with ≥10 mm change from baseline in STS at day 28

Note: The FDA-approved dosage of varenicline solution nasal spray is 0.03 mg BID.3 The results are derived from a posthoc analysis. All comparisons made with the control group.​ No formal statistical comparisons were performed for the 0.006 mg dose versus control.2
FDA, Food and Drug Administration; STS, Schirmer’s test score; VNS, varenicline solution nasal spray.
1. ONSET-1 Oyster Point Pharma, Inc. Data on file; 2. Wirta D. et al. Cornea. 2022;41:1207–1216; 3. 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

Mean change in EDS from baseline in clinic to day 281,2

Note: The FDA-approved dosage of varenicline solution nasal spray is 0.03 mg BID.3 LS means were derived from ANCOVA model with treatment, site, and baseline EDS as covariates. The results are derived from a posthoc analysis. All comparisons made with the control group. No formal statistical comparisons were performed for the 0.006 mg dose versus control.2
ANCOVA, analysis of covariance; CI, confidence interval; EDS, eye dryness score; LS, least squares; VNS, varenicline solution nasal spray.
1. ONSET-1 Oyster Point Pharma, Inc. Data on file; 2. Wirta D. et al. Cornea. 2022;41:1207–1216; 3. 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

Mean change in EDS from baseline to day 21 (5 minutes post-treatment) in the CAE®

Note: The FDA-approved dosage of varenicline solution nasal spray is 0.03 mg BID.2 Least squares means were derived from ANCOVA model with treatment, site, and baseline EDS as covariates. The results are derived from a post hoc analysis. All comparisons made with the control group. No formal statistical comparisons were performed for the 0.006 mg dose versus control.1 *Oyster Point Pharma, Inc. Data on file.
ANCOVA, analysis of covariance; CAE®, controlled adverse environment; CI, confidence interval; EDS, eye dryness score; VNS, varenicline solution nasal spray.
1. Wirta D. et al. Cornea. 2022;41:1207–1216; 2. 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.2 *Data presented as n (%). VNS, varenicline solution nasal spray​.
1. Wirta D. et al. Cornea. 2022;41:1207–1216; 2. TYRVAYA® (varenicline solution) nasal spray. Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/213978s005lbl.pdf.