PMID- 30965064
OWN - NLM
STAT- MEDLINE
DCOM- 20200306
LR  - 20200306
IS  - 1549-4713 (Electronic)
IS  - 0161-6420 (Linking)
VI  - 126
IP  - 9
DP  - 2019 Sep
TI  - A Phase 3, Randomized, Double-Masked Study of OTX-101 Ophthalmic Solution 0.09% 
      in the Treatment of Dry Eye Disease.
PG  - 1230-1237
LID - S0161-6420(18)31322-8 [pii]
LID - 10.1016/j.ophtha.2019.03.050 [doi]
AB  - PURPOSE: To evaluate the safety and efficacy of OTX-101, a novel aqueous 
      nanomicellar formulation of cyclosporine (0.09%), in the treatment of patients 
      with dry eye disease (DED). DESIGN: A randomized, multicenter, 
      vehicle-controlled, double-masked, phase 3 clinical trial. PARTICIPANTS: Adults 
      (18-90 years of age) with a history and clinical diagnosis of DED, a global 
      symptom score of 40 or more (range, 0-100), and a lissamine green conjunctival 
      staining score of 3 or more and 9 or less (range, 0-12) in at least 1 eye. 
      METHODS: Eligible patients entered a run-in period of 14 to 20 days in which all 
      patients administered vehicle twice daily. Patients who remained eligible at the 
      baseline (day 0) visit were randomized in a 1:1 ratio to twice-daily treatment 
      with OTX-101 0.09% or vehicle for 84 days. MAIN OUTCOME MEASURES: Efficacy 
      assessments included signs (unanesthetized Schirmer tear test, corneal and 
      conjunctival staining) and symptoms (global symptom score) of DED. The primary 
      end point was the proportion of eyes with a clinically meaningful improvement 
      (increase of >/=10 mm) in Schirmer test score at day 84. Safety evaluations 
      included adverse events (AEs), visual acuity, and intraocular pressure 
      monitoring, slit-lamp, dilated ophthalmoscopy, and fundus examinations. RESULTS: 
      A total of 744 patients were randomized and received study medication (371 to 
      OTX-101 0.09% and 373 to vehicle). The primary end point was achieved; a 
      significantly greater percentage of eyes in the OTX-101 0.09% treatment group 
      achieved an increase of 10 mm or more in the Schirmer test score at day 84 
      (OTX-101 0.09%, 16.6%; vehicle, 9.2%; P < 0.001). Significant improvements 
      relative to vehicle also were observed for corneal (days 28, 56, and 84) and 
      conjunctival (days 56 and 84) staining. The global symptom score was reduced from 
      baseline in both treatment groups by approximately 30%; however, no significant 
      separation between groups was observed. The OTX-101 0.09% formulation was well 
      tolerated. Treatment-emergent AEs were primarily mild in intensity. CONCLUSIONS: 
      Clinically and statistically significant improvements in tear production and 
      ocular surface integrity were observed in patients treated with OTX-101 0.09% for 
      DED.
CI  - Copyright (c) 2019 American Academy of Ophthalmology. Published by Elsevier Inc. 
      All rights reserved.
FAU - Goldberg, Damien F
AU  - Goldberg DF
AD  - Wolstan & Goldberg Eye Associates, Torrance, California. Electronic address: 
      goldbed@hotmail.com.
FAU - Malhotra, Ranjan P
AU  - Malhotra RP
AD  - Ophthalmology Associates, Cornea and LaserVision Institute, St. Louis, Missouri.
FAU - Schechter, Barry A
AU  - Schechter BA
AD  - Florida Eye Microsurgical Institute, Boynton Beach, Florida.
FAU - Justice, Angela
AU  - Justice A
AD  - Sun Pharmaceutical Industries, Ltd., Princeton, New Jersey.
FAU - Weiss, Sidney L
AU  - Weiss SL
AD  - i-Novion, Inc., Randolph, New Jersey.
FAU - Sheppard, John D
AU  - Sheppard JD
AD  - Virginia Eye Consultants and Eastern Virginia Medical School, Norfolk, Virginia.
LA  - eng
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20190406
PL  - United States
TA  - Ophthalmology
JT  - Ophthalmology
JID - 7802443
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Ophthalmic Solutions)
RN  - 83HN0GTJ6D (Cyclosporine)
SB  - IM
CIN - Ophthalmology. 2020 Jul;127(7):e43-e44. PMID: 32564818
CIN - Ophthalmology. 2020 Jul;127(7):e43. PMID: 32564819
MH  - Administration, Ophthalmic
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Cyclosporine/adverse effects/*therapeutic use
MH  - Double-Blind Method
MH  - Dry Eye Syndromes/*drug therapy/physiopathology
MH  - Female
MH  - Humans
MH  - Immunosuppressive Agents/adverse effects/*therapeutic use
MH  - Intraocular Pressure/drug effects/physiology
MH  - Male
MH  - Middle Aged
MH  - Ophthalmic Solutions/therapeutic use
MH  - Surveys and Questionnaires
MH  - Tears/physiology
MH  - Treatment Outcome
MH  - Visual Acuity/drug effects/physiology
MH  - Young Adult
EDAT- 2019/04/10 06:00
MHDA- 2020/03/07 06:00
CRDT- 2019/04/10 06:00
PHST- 2018/05/17 00:00 [received]
PHST- 2019/03/08 00:00 [revised]
PHST- 2019/03/29 00:00 [accepted]
PHST- 2019/04/10 06:00 [pubmed]
PHST- 2020/03/07 06:00 [medline]
PHST- 2019/04/10 06:00 [entrez]
AID - S0161-6420(18)31322-8 [pii]
AID - 10.1016/j.ophtha.2019.03.050 [doi]
PST - ppublish
SO  - Ophthalmology. 2019 Sep;126(9):1230-1237. doi: 10.1016/j.ophtha.2019.03.050. Epub 
      2019 Apr 6.