Skip to content

  • About CRIS
  • Search
    • Basic Search
    • Advanced Search
    • Search by Topics
      • Condition(s)/Problem(s)
      • Intervention Type
      • Phase
    • Recently Registered
    • Recently Updated
  • FAQ
  • Statistics
  • Registration Data Set

Contact Us

criskorea@korea.kr
  • Status : Approved
    • First Submitted Date : 2016/11/23
    • Registered Date : 2016/12/23
    • Last Updated Date : 2019/08/20
Background Information
1.Background  
CRIS Registration Number KCT0002180 
Unique Protocol ID KCDSG-CCD-01 
Public/Brief Title Prospective clinical trial to evaluate efficacy, safety and usability of nanoemulsion cyclosporin 0.05%, emulsion cyclosporin 0.05% and diquafosol 3% in dry eye patients 
Scientific Title A multicenter, randomized, partial double blind, active control, parallel clinical trial to evaluate the efficacy, safety and usability of cyclosporin ophthalmic nanoemulsion 0.05% compared with cyclosporin ophthalmic emulsion 0.05% and diquafosol ophthalmic solution 3%  
Acronym CCD study 
MFDS Regulated Study No
IND/IDE Protocol No
Registered at Other Registry No
Healthcare Benefit
Approval Status
Not applicable
Institutional Review Board Information
2. Institutional Review Board/Ethics Committee  
Board Approval Status Submitted approval 
Board Approval Number XC16MIMV0056S 
Approval Date 2016-08-09 
Institutional Review Board  
- Name SCMC IRB (Sungmo Catholic Medical Center Institutional Review Board)  
- Address 10, 63-ro, Yeongdeungpo-gu, Seoul 
- Telephone 02-3779-2011 
Data Monitoring Committee No  
Contact Details
3.Contact Details  
Contact Person for Principal Investigator / Scientific Queries
- Name Hyun-Seung Kim 
- Title M.D. 
- Telephone +82-2-1661-7575 
- Affiliation The Catholic University of Korea, Yeouido St. Mary's Hospital 
- Address 10, 63-ro Yeongdeungpo-gu, Seoul, Korea 
Contact Person for Public Queries
- Name Hyun-Seung Kim 
- Title M.D. 
- Telephone +82-2-3779-1848 
- Affiliation The Catholic University of Korea, Yeouido St. Mary's Hospital 
- Address 10, 63-ro Yeongdeungpo-gu, Seoul, Korea 
Contact Person for Updating Information
- Name Hanna Kim 
- Title TM 
- Telephone +82-2-799-0198 
- Affiliation Taejoon Pharm 
- Address 8, Daesagwan-ro 31-gil, Yongsan-gu, Seoul, Korea 
Status
4. Status Status  
Study Site Multi-center (Number of center : 12)
Overall Recruitment Status Completed  
Date of First Enrollment 2016-10-21 , Actual
Target Number of Participant 227
Primary Completion Date 2017-05-30 , Actual
Study Completion Date 2017-07-03 , Actual
Recruitment Status by Participating Study Site 1 
- Name of Study Site Samsung Medical Center 
- Recruitment Status Completed  
- Date of First Enrollment 2016-12-13 , Actual
Recruitment Status by Participating Study Site 2 
- Name of Study Site Yonsei University Health System, Gangnam Severance Hospital 
- Recruitment Status Completed  
- Date of First Enrollment 2016-11-21 , Actual
Recruitment Status by Participating Study Site 3 
- Name of Study Site Koera University Guro Hospital 
- Recruitment Status Completed  
- Date of First Enrollment 2016-11-29 , Actual
Recruitment Status by Participating Study Site 4 
- Name of Study Site The Catholic University of Korea, Yeouido St. Mary's Hospital 
- Recruitment Status Completed  
- Date of First Enrollment 2016-11-09 , Actual
Recruitment Status by Participating Study Site 5 
- Name of Study Site Kangbuk Samsung Medical Center 
- Recruitment Status Completed  
- Date of First Enrollment 2016-10-25 , Actual
Recruitment Status by Participating Study Site 6 
- Name of Study Site Chonnam National University Hospital 
- Recruitment Status Completed  
- Date of First Enrollment 2016-11-08 , Actual
Recruitment Status by Participating Study Site 7 
- Name of Study Site Inje University Ilsan Paik Hospital 
- Recruitment Status Completed  
- Date of First Enrollment 2017-01-11 , Actual
Recruitment Status by Participating Study Site 8 
- Name of Study Site Kyungpook National University Hospital 
- Recruitment Status Completed  
- Date of First Enrollment 2016-10-21 , Actual
Recruitment Status by Participating Study Site 9 
- Name of Study Site Seoul National University Hospital 
- Recruitment Status Completed  
- Date of First Enrollment 2016-10-31 , Actual
Recruitment Status by Participating Study Site 10 
- Name of Study Site Yonsei University Health System, Severance Hospital 
- Recruitment Status Completed  
- Date of First Enrollment 2016-12-08 , Actual
Recruitment Status by Participating Study Site 11 
- Name of Study Site Asan Medical Center 
- Recruitment Status Completed  
- Date of First Enrollment 2016-10-31 , Actual
Recruitment Status by Participating Study Site 12 
- Name of Study Site The Catholic University of Korea, Bucheon St. Mary's Hospital 
- Recruitment Status Completed  
- Date of First Enrollment 2016-11-18 , Actual
Source of Monetary / Material Support 정보
5. Source of Monetary/Material Support  
Source of Monetary/Material Support1 
- Organization Name Taejoon Pharm 
- Organization Type Pharmaceutical Company  
- Project ID KCDSG-CCD-01 
Sponsor Organization
6. Sponsor Organization  
Sponsor Organization 1 
- Organization Name The Catholic University of Korea, Yeouido St. Mary's Hospital 
- Organization Type Medical Institute  
Study Summary
7. Study Summary  
Lay Summary Dry eye syndrome(DES) is a multifactorial disease easily encountered clinically with 14~30% of reported prevalence but not easily treated properly in practice leaving more way to go.
Clinically for DES, conservative therapy focusing to reserve tear amount by supplying artificial tears and/or blocking lacrimal duct flow surgically has been used widely. And, along with DEWS(international Dry Eye Workshop) 2007 guidance, anti-inflammatory therapy using cyclosporin etc has been the choice. More recently, secretagogues like diquafosol has introduced with novel approach to promote water and mucin secretion from goblet cells/conjunctival epithelial cells.
As cyclosporin product, an emulsion formulation has been used for the last over 10 years with some complains and/or inconveniences like mandated re-mixing before use, burning sensation or blurred vision after instillation into the eye. To overcome these, nano-technology has introduced and several nano-emulsion type cyclosprin ophthalmic products were approved for market.
On the other hand, two popular active ingredients, cyclosporin and diquafosol, seems to share common acting point of goblet cell, but, with limited reports on.
On these background, this muticenter study is designed for two goals, to compare cyclosporin and diquafosol and to compare two different cyclosporin products with different particle size.
As, nano-emulsion cyclosporin ophthalmic product, CYPORIN®N 0.05% is selected expecting additional advantage containing artificial tear(CMC) and mucoadhesive polymer, Xanthan gum.  
Study Design 정보
8. Study Design  
Study Type Interventional Study 
Study Purpose Treatment
Phase Phase4 
Intervention Model Parallel  
Blinding/Masking Double 
Blinded Subject Subject, Investigator 
Allocation RCT 
Intervention Type Drug  
Intervention Description 3 arms
(1st arm) Nanoemulsion cyclosporine 0.05% ophthalmic soln. treatment arm: CYPORIN®N 0.05%, 1 drop/time, 2 times/day, 12 weeks, ophthalmic
(2nd arm) Emulsion cyclosporine 0.05% ophthalmic soln. treatment arm: RESTASIS® 0.05%, 1 drop/time, 2 times/day, 12 weeks, ophthalmic
(3rd arm) Diquafosol tetrasodium ophthalmic soln. treatment arm: Diquas® 3%, 1 drop/time, 6 times/day, 12 weeks, ophthalmic  
Number of Arms
Arm 1 Arm Label Nanoemulsion cyclosporine 0.05% ophthalmic soln. treatment Arm 
Target Number of Participant 80 
Arm Type Experimental 
Arm Description 1 drop/time, 2 times/day, 12 weeks (artificial tear 1 drop/time as available co-medication with recommendation of at least 4 times/day) 
Arm 2 Arm Label Emulsion cyclosporine 0.05% ophthalmic soln. treatment Arm 
Target Number of Participant 80 
Arm Type Active comparator 
Arm Description 1 drop/time, 2 times/day, 12 weeks (artificial tear 1 drop/time as available co-medication with recommendation of at least 4times/day) 
Arm 3 Arm Label Diquafosol tetrasodium 3% ophthalmic soln. treatment Arm 
Target Number of Participant 80 
Arm Type Active comparator 
Arm Description 1 drop/time, 6 times/day, 12 weeks (artificial tear 1 drop/time as available co-medication) 
Subject Eligibility Information
9. Subject  
Condition(s)/Problem(s) * Diseases of the eye and adnexa
Dry eye symdrome  
Rare Disease No
Inclusion
Criteria
Gender Both 
Age 19 Year ~ No Limit
Description 1) ≥19 years of age
2) moderate to severe Dry eye syndrome (Corneal BFS score(NEI scale) ≥ 4 and ≤ 10 sec on TBUT)
3) volentary agreement with signed informed consent  
Exclusion Criteria 1. cyclosporine or diquafosol use in any form(systemic, topical) within 4 weeks
2. medical condition or history within 4 weeks to be treated with topical agents besides artifical tears(glaucoma, ocular allergy, ocular inflammation/infectious disease, etc)
3. new start or medication change within 4 weeks for systemic drugs with probable effect on dry eye codition
4. sjogren syndrome
5. plan to wear contact lens during the study period
6. current or history of ocular disorders possibly affecting the study results(ocular surgery, trauma, diseases)
1) entropion, blepharelosis, blepharoplegia
2) ocular surgery history within 4 weeks or plan during the study period like punctal plug, punctal closure etc
3) herpetics keratopathy, conjunctival scarring by cicatricial keratoconjunctivitis, pterygium, congenital lacrimal gland shortage, neurogenic keratitis, keratoconus, corneal transplantation
7. known hypersensitivity to study medications
8, pregnancy or lactation
9. investigator's judge of inappropiation  
Healthy Volunteers No
Outcome Measure(s) Information
10. Outcome Measure(s)  
Type of Primary Outcome Efficacy 
Primary Outcome(s) 1 
- Outcome Changes in corneal conjunctival staining score 
- Timepoint 12 week 
Secondary Outcome(s) 1 
- Outcome Changes in corneal conjunctival staining score  
- Timepoint 4 week 
Secondary Outcome(s) 2 
- Outcome Changes in corneal staining score 
- Timepoint 4 week, 12 week 
Secondary Outcome(s) 3 
- Outcome Changes in conjunctival staining score 
- Timepoint 4 week, 12 week 
Secondary Outcome(s) 4 
- Outcome Changes in TBUT (tear break-up time) 
- Timepoint 4 week, 12 week 
Secondary Outcome(s) 5 
- Outcome Changes in schirmer I test score  
- Timepoint 4 week, 12 week 
Secondary Outcome(s) 6 
- Outcome Changes in OSDI(ocular surface disease index) 
- Timepoint 4 week, 8 week, 12 week 
Secondary Outcome(s) 7 
- Outcome Patient global evalution 
- Timepoint 4 week, 8 week, 12 week 
Secondary Outcome(s) 8 
- Outcome tear mucin level change [exploratory endpoint] 
- Timepoint 4 week 
Secondary Outcome(s) 9 
- Outcome tear cytokine level change [exploratory endpoint] 
- Timepoint 4 week 
Study Results and Publication Information
11. Study Results and Publication
Result Registerd Yes
Published
Final Enrollment Number 227
Number of Publication
Publications 1 Chang Hyun Park, Hyung Keun Lee, Mee Kum Kim, Eun Chul Kim, Jae Yong Kim, Tae-im Kim, Hong Kyun Kim, Jong Suk Song, Kyung Chul Yoon, Do Hyung Lee, Tae-Young Chung, Chul Young Choi, Hyun Seung Kim. Comparison of 0.05% cyclosporine and 3% diquafosol solution for dry eye patients: a randomized, blinded, multicenter clinical trial. BMC Ophthalmology. SCI. 2019-06-17 ,   VOL : 0   page : 0 ~ 0
(https://doi.org/10.1186/s12886-019-1136-8)
Publications 2 Chang Hyun Park, Mee Kum Kim, Eun Chul Kim, Jae Yong Kim, Tae-Im Kim, Hong Kyun Kim, Jong Suk Song, Kyung-Chul Yoon, Do Hyung Lee, Hyung Keun Lee, Tae-Young Chung, Chul Young Choi, Hyun Seung Kim . Efficacy of Topical Cyclosporine Nanoemulsion 0.05% Compared with Topical Cyclosporine Emulsion 0.05% and Diquafosol 3% in Dry Eye. Korean Journal Ophthalmology. Non SCI. 2019-08-05 ,   VOL : 33   page : 343 ~ 352
(https://doi.org/10.3341/kjo.2018.0116)
Results Upload  
Date of Posting Results
Protocol URL or File Upload  
Brief Summary Primary endpoints showed statistically significant improvements in all groups. Primary endpoints were -6.60 for the CN group, -5.28 for the CE group, and -6.63 for the DQ group (National Eye Institute scale from 0 to 33), verifying the non-inferiority of CN compared to CE (95% confidence interval, -0.15 to 2.80, Δ>-2.88). In intergroup comparison between CN and CE groups, the CN group had significantly more decreased conjunctival staining score at week 12. Intergroup comparison between CN and DQ groups showed consistent statistically significant improvements in TBUT and Schirmer test in the CN group. In the DQ group, TBUT showed late statistically significant improvement at week 12 and Schirmer test showed relatively short-term statistically significant improvement at week 4.
Conclusions: Cyclosporine nanoemulsion 0.05% was equivalently efficient compared to cyclosporine emulsion 0.05% and diquafosol sodium 3%. In addition, CN showed significant improvements in several parameters for treatment of dry eyes.  
Sharing of Study Data Information
12. Sharing of Study Data(Deidentified Individual-Patient Data, IPD)
Sharing Statement No