Effect of Cequa™ in Subjects With Dry Eye Disease That Is Currently Inadequately Controlled While on Cyclosporine 0.05% Ophthalmic Emulsion
Phase: PHASE4
Conditions: Dry Eye Disease
Sponsor: Sun Pharmaceutical Industries Limited

Official Title: Effect of Cequa™ in Subjects with Dry Eye Disease That Is 
Currently Inadequately Controlled While on Cyclosporine 0.05% Ophthalmic 
Emulsion 
Document: Clinical Study Protocol 
NCT number: NCT04357795 
Date: 11-Dec-2019

Effect of Cequa TM in Subjects With Dry Eye Disease That 
Is Currently Inadequately Controlled While on 
Cyclosporine 0.05% Ophthalmic Emulsion 
Protocol Number: OTX101-2019-001 
Sponsor: Sun Pharma Global FZE 
Version Number: 1.0 
11 December 2019 
Statement of Compliance: 
The trial will be conducted in accordance with International Conference on Harmonisation (ICH) 
Good 
Clinical Practice (GCP), and applicable United States (US) Code of Federal Regulations (CFR). The 
Principal Investigator will assure that no deviation from, or changes to, the protocol will take 
place without prior agreement from the Sponsor and documented approval from the 
Institutional Review Board (IRB), except where necessary to eliminate an immediate hazard(s) 
to the trial participants. All personnel involved in the conduct of this study have GCP training. 
The study is conducted also under the Declaration of Helsinki. The protocol, informed consent 
form(s) [ICF(s)], recruitment materials, and all participant materials will be submitted to the IRB 
for review and approval. Approval of both the protocol and the consent form must be obtained 
before any participant is enrolled. Any amendment to the protocol will require review and 
approval by the IRB before the changes are implemented to the study. All changes to the 
consent form will be IRB approved; a determination will be made regarding whether a new 
consent needs to be obtained from participants who provided consent using a previously 
approved consent form. 
Protocol Summary: 
SYNOPSIS 
Title: Effect of Cequa TM in Subjects With Dry Eye Disease That Is Currently Inadequately 
Controlled While on Cyclosporine 0.05% Ophthalmic Emulsion 
Study Description: 
Objectives: 
This is a phase 4, multicenter, open-label, single-arm, 12-week study of subjects with dry eye 
disease (DED) that is inadequately controlled by cyclosporine (CsA) 0.05% ophthalmic emulsion. 
Treatment will be one drop of CsA 0.09% ophthalmic solution (Cequa) in each eye twice daily 
(BID) for 12 weeks. The study hypothesis is that CsA 0.09% ophthalmic solution will show 
improved clinical benefit in subjects whose dry eye signs and/or symptoms are inadequately 
controlled while on CsA 0.05% ophthalmic emulsion.  

Primary: to evaluate improvement in the signs and/or symptoms of DED following use of CsA 
0.09% ophthalmic solution in subjects whose DED is inadequately controlled by CsA 0.05% 
ophthalmic emulsion. 
Secondary: to evaluate changes in additional signs and symptoms over the 12-week course of 
Cequa therapy. 
 
Statistical Analyses: 
Neither masking nor randomization will be employed for operation of this study; this is an 
open-label study 
• Primary efficacy endpoints will be analyzed using descriptive statistics and restricted 
maximum likelihood repeated measures mixed model (REMLMMRM) models. 
• Multiplicity adjustments of observed significance levels for primary efficacy endpoints will be 
presented. 
 
Study Population: 
Subjects will have DED that is not adequately controlled (ie, still symptomatic and/or still 
exhibiting signs of disease) by current treatment with CsA 0.05% ophthalmic emulsion. Eligible 
subjects must have been taking CsA 0.05% ophthalmic emulsion treatment for at least 3 
months prior to the Screening/Baseline visit. However, subjects who have failed prior 
treatment with CsA 0.05% ophthalmic emulsion will be excluded from the study. 
 
Inclusion/Exclusion Criteria: 
Inclusion Criteria: 
1. Male or female subjects with a history of bilateral dry eye disease for a period of at least 
3 months. 
2. Aged of at least 18 years. 
3. Subjects with total corneal fluorescein staining ≥6 or corneal fluorescein staining in an 
individual zone ≥2 as per National Eye Institute Grading Scale. 
4. Subjects with modified symptom assessment in dry eye global symptom score, ≥40 using 
visual analogue scale. 
5. Subjects with best-corrected visual acuity 20/200 or better in both eyes at the 
Screening/Baseline visit 
Exclusion Criteria: 
1. Subjects who have used cyclosporine 0.05% ophthalmic emulsion in both eyes for less 
than 3 months prior to the Screening/Baseline visit. 
2. Subjects with history of treatment failure with cyclosporine 0.05% ophthalmic emulsion. 
3. Subjects who have active seasonal and/or perennial allergic conjunctivitis in either eye. 
4. Subjects who had already Use initiated any systemic or topical ocular medication. 
 
 

Justification of Dose: 
Cyclosporine 0.09% ophthalmic solution (Cequa) is approved by the FDA to increase tear 
production in patients with KCS (Cequa prescribing information, 2018). It is to be dosed as 1 
drop BID (approximately 12 hours apart) into each eye. Therefore, the dosing in the current 
phase 4 study will match the approved dosing regimen. 
 
Overall Design: 
This is a phase 4, multicenter, open-label, single-arm, 12-week study of subjects with DED that 
is inadequately controlled by CsA 0.05% ophthalmic emulsion. Study subjects will be male or 
female, at least 18 years of age, with a history and clinical diagnosis of bilateral DED for a period 
of at least 3 months, corrected BCVA of 20/200 or better in both eyes at the Screening/Baseline 
visit, and a willingness to discontinue use of all dry eye therapy, aside from continuing any 
existing ATP use. In addition, subjects must have total CFS ~6 (or CFS ~2 in an individual zone) 
and/or a modified SAnDE score ~40.  
At the Screening/Baseline visit, sites will obtain signed informed consent, 
medical/ocular/concomitant medication histories, and demographics, perform a urine 
pregnancy test (for women of childbearing potential only), conduct screening ophthalmic 
examinations, and review inclusion/exclusion criteria. Site staff will dispense study medication, 
provide appropriate instructions for use, and supervise administration of first dose. All enrolled 
subjects will self-administer 1 drop of CsA 0.09% ophthalmic solution in each eye BID for 12 
weeks. Subjects will return at Weeks 4, 8, and 12. In addition, at the Week 12 visit, sites will 
perform a urine pregnancy test (for women of childbearing potential only), and subjects will 
answer a treatment preference question. At each visit, concomitant medications will be 
updated, adverse events (AEs) will be collected, the subject's daily diary on the frequency of 
ATP and CsA 0.09% ophthalmic solution use will be examined, subjects will answer a 
compliance question, and actual daily use entered into electronic data capture (EDC). 
 
Study Record Retention: 
Investigators should retain study-related records at the site for a minimum of 5 years after 
study closeout.