PMID- 30858682
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220408
IS  - 1177-5467 (Print)
IS  - 1177-5483 (Electronic)
IS  - 1177-5467 (Linking)
VI  - 13
DP  - 2019
TI  - A phase 2 randomized, double-masked, placebo-controlled study of novel 
      nonsystemic kinase inhibitor TOP1630 for the treatment of dry eye disease.
PG  - 261-275
LID - 10.2147/OPTH.S189039 [doi]
AB  - PURPOSE: To evaluate the safety and efficacy of topical TOP1630, a novel 
      nonsystemic kinase inhibitor, in dry eye disease (DED). PATIENTS AND METHODS: A 
      randomized, double-masked, parallel-group trial of 0.1% TOP1630 ophthalmic 
      solution TID or placebo (vehicle without active drug) was conducted in DED 
      subjects (n=61). Key eligibility criteria consistent with enrolling a moderate to 
      severe DED population included >6 months DED history; OSDI((c)) score >/=18; 
      Schirmer's test score </=10 and >/=1 mm/5 minutes; tear film break-up time >1 and <7 
      seconds; and dry eye exacerbation in corneal staining and ocular discomfort in a 
      Controlled Adverse Environment (CAE((R))). After a 7-day run-in period with placebo 
      TID, eligible subjects were randomized to TOP1630 or placebo for 28 days. No 
      supplemental artificial tears or rescue medication were allowed. RESULTS: TOP1630 
      was safe, well-tolerated, and efficacious in treating DED symptoms and signs. No 
      serious adverse events (AEs) or withdrawals due to treatment emergent AEs 
      occurred. Drop comfort scores showed TOP1630 to be comfortable and comparable 
      with placebo. Significant symptom improvements were seen for TOP1630 vs placebo 
      for ocular discomfort (P=0.02 post-CAE), grittiness/foreign body sensation (on 
      four independent assessment scales, each P<0.05), worst DED symptom (diary, 
      P=0.06), and ocular pain (VAS, P=0.03). Sign improvements were seen for total 
      ocular surface (all regions), corneal sum, and conjunctival sum staining with 
      TOP1630 compared with placebo (each P<0.05). CONCLUSION: TOP1630 had placebo-like 
      tolerability and produced improvements in multiple symptom and sign endpoints in 
      both environmental and challenge settings. The emergent TOP1630 benefit-risk 
      profile for DED treatment is highly favorable and supports further development.
FAU - Taylor, Mike
AU  - Taylor M
AD  - TopiVert Pharma Limited, London, UK, mike.taylor@topivert.com.
FAU - Ousler, George
AU  - Ousler G
AD  - Ora Inc., Andover, MA, USA.
FAU - Torkildsen, Gail
AU  - Torkildsen G
AD  - Andover Eye Associates, Andover, MA, USA.
FAU - Walshe, Claire
AU  - Walshe C
AD  - TopiVert Pharma Limited, London, UK, mike.taylor@topivert.com.
FAU - Fyfe, Matthew C T
AU  - Fyfe MCT
AD  - TopiVert Pharma Limited, London, UK, mike.taylor@topivert.com.
FAU - Rowley, Adele
AU  - Rowley A
AD  - TopiVert Pharma Limited, London, UK, mike.taylor@topivert.com.
FAU - Webber, Steve
AU  - Webber S
AD  - TopiVert Pharma Limited, London, UK, mike.taylor@topivert.com.
FAU - Sheppard, John D
AU  - Sheppard JD
AD  - Virginia Eye Consultants, Norfolk, VA, USA.
FAU - Duggal, Ajay
AU  - Duggal A
AD  - TopiVert Pharma Limited, London, UK, mike.taylor@topivert.com.
LA  - eng
PT  - Journal Article
DEP - 20190212
PL  - New Zealand
TA  - Clin Ophthalmol
JT  - Clinical ophthalmology (Auckland, N.Z.)
JID - 101321512
PMC - PMC6387610
OTO - NOTNLM
OT  - DED
OT  - TOP1630
OT  - dry eye
OT  - ocular inflammation
COIS- Disclosure MT, CW, MCTF, AR, and SW are employees of TopiVert Pharma Limited. GO, 
      JDS, and AD are consultants of TopiVert Pharma Limited. GO is an employee of Ora 
      Inc. GT reports grants from TopiVert Pharma Limited, during the conduct of the 
      study; grants from Oculeve, Allergan, ReGentree, Hanall, Mimetogen, AB2Bio, 
      Aldeyra, Axerovision, BRIM, Diagnostear, Novaliq, Oyster point and grants, 
      personal fees from Ora, Inc., outside the submitted work. MCTF reports personal 
      fees from TopiVert Pharma Limited, outside the submitted work. MCTF has a patent 
      US9499486 issued. JDS reports grants from TopiVert Pharma Limited, during the 
      conduct of the study; grants from Allergan, Shire, Bausch & Lomb, Sun Pharma and 
      Novaliq, outside the submitted work. The authors report no other conflicts of 
      interest in this work.
EDAT- 2019/03/13 06:00
MHDA- 2019/03/13 06:01
PMCR- 2019/02/12
CRDT- 2019/03/13 06:00
PHST- 2019/03/13 06:00 [entrez]
PHST- 2019/03/13 06:00 [pubmed]
PHST- 2019/03/13 06:01 [medline]
PHST- 2019/02/12 00:00 [pmc-release]
AID - opth-13-261 [pii]
AID - 10.2147/OPTH.S189039 [doi]
PST - epublish
SO  - Clin Ophthalmol. 2019 Feb 12;13:261-275. doi: 10.2147/OPTH.S189039. eCollection 
      2019.