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WHAT WILL HAPPEN IN THIS STUDY?
If you meet the requirements and agree to join, participation will last approximately 13 weeks which will include 6 visits to the study clinic.

Participants in this study will be assigned randomly (like pulling numbers out of a hat) to receive either the study medicine or placebo (a medication with no active ingredients).

​​​They will have a 3/4 chance of receiving the study medicine and 1/4 chance of receiving only placebo.

The study treatment will be given as self administered eye drops twice daily in the morning and evening for 12 weeks.

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WHY IS THIS CLINICAL STUDY IMPORTANT?
Your participation in this clinical study may help us to better understand dry eye disease which could help others with dry eye disease in the future.

Clinical trials (or studies) look for new ways to progress science and develop potential treatment options.

They are designed to help us understand whether potential new medicines are safe and work to help people with the disease or condition being studied.

Even if participants don’t directly benefit from the results of the clinical trial, the information collected can help others and add to scientific knowledge. People who take part in clinical trials are vital to the process of improving medical care.


Ï㽶ֱ²¥ objectives:

1. To evaluate the safety and tolerability of Cevimeline Ophthalmic Solution compared to vehicle in subjects with dry eye disease (DED) over a 12-week treatment period.
2. To evaluate the efficacy of Cevimeline Ophthalmic Solution compared to vehicle in subjects with dry eye disease (DED) over a 12-week treatment period.
   

Ï㽶ֱ²¥ population:
The study population will consist of subjects with signs and symptoms of moderate to severe DED.

Number of subjects:
Approximately 120 subjects will be randomized to Cevimeline Ophthalmic Solution (1%, 2% and 4%) or vehicle at a 1:1:1:1 ratio.

Investigational Product (IP):

• Cevimeline Ophthalmic Solution (1%, 2% and 4%)
• Vehicle Ophthalmic Solution
  

Route and Duration of Administration:
Investigational Product (IP) will be administered to each eye BID, morning and evening (at least 6-hour interval), for up to 12 weeks.

Ï㽶ֱ²¥ Design:
This study will be a randomized, vehicle-controlled, double-masked, multiple-dose, parallel-group study to evaluate the efficacy, safety and tolerability of repeat dosing of Cevimeline Ophthalmic Solution compared to the vehicle in subjects with DED. The study will consist of two periods as follows:

1. Single-Masked Screening/ Vehicle Run-In Period ( 14 ±1 days prior to randomization)
2. Double-Masked Treatment Period (Day 1 to Day 85)

Single-Masked Screening/Vehicle Run-In Period:
At the screening visit/Visit 1 (Day 1 minus 14 days), subjects who are eligible according to the inclusion and exclusion criteria will begin a 14-day run-in period during which they will self-administer 1 drop of single-masked vehicle to each eye BID, morning and evening (at least 6-hour interval). At the time of the screening visit/Visit 1, subjects will be instructed to discontinue all over the counter (OTC) and prescription topical ophthalmic medications except for the vehicle or study drug throughout the study.
Double-Masked Treatment Period:
At Baseline/Visit 2 (Day 1), subjects who continue fulfilling inclusion/exclusion criteria will be randomized to study drug or vehicle.
Approximately 120 subjects will be randomized. Subjects will be randomized to one of the following 4 treatment groups in a 1:1:1:1 ratio as follows:

• Group 1: 1% Cevimeline Ophthalmic Solution self-administered BID, morning and evening
• Group 2: 2% Cevimeline Ophthalmic Solution self-administered BID, morning and evening
• Group 3: 4% Cevimeline Ophthalmic Solution self-administered BID, morning and evening
• Group 4: Vehicle self-administered BID, morning and evening
  

Following randomization, subjects being masked to treatment assignments will be instructed to self-administer 1 drop of IP into each eye twice daily, morning and evening (at least 6-hour interval). Subjects will be instructed to return to the clinic to be evaluated at Day 15 (Visit 3), Day 29 (Visit 4), Day 57 (Visit 5), and Day 85 (Visit 6).
During the treatment period, only the IP is allowed to be administered to subjects.

Inclusion Criteria:
At both Visit 1 (Screening) and Visit 2 (Baseline/Randomization), subjects must meet all following criteria:

1. Ìý18 years of age or older (regardless of gender).
2. Provide written informed consent.
3. Willing and able to follow instructions and be available for required study visits during the study.
4. VA (Visual Acuity) of 20/100 or better in both eyes.
5. Ongoing moderate to severe DED supported by a previous clinical diagnosis or a self-reported history of subjective complaints for at least 6 months prior to the screening visit, and meet all the following criteria in at least one eye (the same eye) at Visit 1 and Visit 2:
   - tCFS score between 4 and 16, inclusive
   - Schirmer tear production test without anesthesia of 1-10 mm/5 mins
   - Ocular dryness score (0-100 points VAS) ≥30
   - SANDE score of at least 25
6. Have been using artificial tears at least 2 times per day for at least 28 days prior to the screening visit (self-reported).
7. Willing to withhold all prescriptions of topical ophthalmic medications and other DED medicine including herbal medicine, heated eye massage, except the artificial tears as a rescue drug, from the screening visit (Visit 1) and for the duration of the study.
8. Normal eyelid and eyelash anatomy.
   
   

Exclusion Criteria:

Subjects who meet any of the following criteria will not be allowed to enter this study.

1. Known hypersensitivity or contraindication to the study drug or its components.
2. Ongoing ocular infection (bacterial, viral, or fungal) at visit 1 or visit 2.
3. Within 14 days prior to the screening visit (Visit 1), have taken or used:
   o Topical ophthalmic, dermatologic or systemic calcineurin inhibitor (e.g. cyclosporine and tacrolimus), including Restasis® Cequa®, and Ikervis®.
   o Topical lifitegrast ophthalmic solution (Xiidra®)
   o Intranasal Tear Neurostimulation (TrueTearâ„¢)
   o Intranasal varenicline (Tyrvaya®)
   o Topical autologous serum
   o Nicotinic acetylcholine receptor (nAChR) agonist [nicotine (NICODERM, NICORETTE, and NICOTROL NS etc.), cytisine (TABEX and DESMOXAN etc.), and varenicline (CHANTIX etc.)]
   o Systemic isotretinoin (Accutane®)
   o P2Y2 receptor agonist, such as Diquafosol (DIQUAS®, SANTEN PHARMACEUTICAL CO., LTD.)
4. Within 84 days prior to the screening visit (Visit 1) have taken/used:
   o Any topical or systemic phosphodiesterase 4 inhibitors
5. Current use of contact lenses or anticipated use during the study.
6. Use of scleral lenses in the 28 days prior to the screening visit or anticipated use during the study.
7. Exposure to an investigational drug within the preceding 28 days prior to the screening visit.
8. History of any ocular surface or anterior segment surgery in the 3 months prior to the screening visit, including but not limited to the PRK (Photo Refractive Keratectomy), LASIK (Laser Assisted in Situ Keratomileusis), SMILE (Small Incision Lenticule Extraction), and IPL (Intense Pulse Light).
9. Within 28 days prior to the screening visit (Visit 1), have altered the dosage or anticipate future alterations to the dose for the following systemic treatments in the duration of the study:
   o Systemic Cevimeline use
   o Systemic corticosteroids
   o Methotrexate
   o Oral macrolides or tetracyclines
   o Systemic androgen or hormone replacement therapy
   o Androgen inhibitors
   o Immunomodulating agents
   
   
10. Current use of any topical ophthalmic medications, eyelash growth medications, eye drops, or gels, except for artificial tears.
11. Current use of any Cannabidiol products.
12. Conjunctival goblet cell deficiency such as from chemical ocular burns, ocular cicatricial pemphigoid, Stevens-Johnson syndrome, ocular graft versus host disease, irradiation, trachoma, or vitamin A deficiency.
13. Presence of trigger factors that, in the opinion of the Investigator, may confound the study data, including but not limited to trichiasis, epithelial basement membrane dystrophy, infectious keratitis, or infectious conjunctivitis.
14. IOP over/equal to 24 mmHg or those are being treated for glaucoma at either screening or randomization visit.
15. History of punctal cauterization.
16. Current use of punctal plugs or anticipated use during the study.
17. Non-Adherence (<70%) with Vehicle Run-In administration counting via (e)diary card.
18. Have a known history of alcohol and/or drug abuse within 1 year prior to the screening visit (Visit 1).
19. Current diagnosis of hepatic insufficiency or clinically meaningful liver function test abnormalities, as determined by the investigator.
20. In the opinion of the investigator or study coordinator, be unwilling or unable to comply with the study protocol or unable to successfully instill eye drops.
21. Women of child-bearing potential are excluded if meeting any of the following:
    o are currently pregnant,
    o having a positive result at urine/serum pregnancy test at screening period,
    o are lactating
22. Are not willing to use an acceptable form of contraception throughout the study (from Visit 1 until Visit 6). Acceptable methods include the use of at least one of the following: intrauterine device (IUD), hormonal (oral, injection, patch, implant, ring), barrier with spermicide, or abstinence.Ìý

If you would like more information on this study please contact the clinical trial coordinator for Professor Stephanie Watson OAM FARVO:

Dr. Ngozi Chidi-Egboka
Email: ngozi.chidiegboka@sydney.edu.au
Tel: +61 2 9382 7595

You will attend this study visit at the Gadigal Clinic, Sydney Eye Hospital.

You will be paid for your time and travel while you are supporting this medical research.

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Ethics committee approval number: HREC2024-06-779-A-5 (REGIS ID: 2024/ETH01169)Ìý