A phase 2 randomized, double-masked, placebo-controlled study of novel nonsystemic kinase inhibitor TOP1630 for the treatment of dry eye disease
Mike Taylor,1 George Ousler,2 Gail Torkildsen,3 Claire Walshe,1 Matthew C T Fyfe,1 Adele Rowley,1 Steve Webber,1 John D Sheppard,4 Ajay Duggal1 1TopiVert Pharma Limited, London, UK; 2Ora Inc., Andover, MA, USA; 3Andover Eye Associates, Andover, MA, USA; 4Virginia Eye Consultants, Norfolk, VA, USA...
Guardado en:
| Autores principales: | , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2019
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/a6447234955b44e08b83b58e5c0fbf7c |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:a6447234955b44e08b83b58e5c0fbf7c |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:a6447234955b44e08b83b58e5c0fbf7c2021-12-02T01:05:46ZA phase 2 randomized, double-masked, placebo-controlled study of novel nonsystemic kinase inhibitor TOP1630 for the treatment of dry eye disease1177-5483https://doaj.org/article/a6447234955b44e08b83b58e5c0fbf7c2019-02-01T00:00:00Zhttps://www.dovepress.com/a-phase-2-randomized-double-masked-placebo-controlled-study-of-novel-n-peer-reviewed-article-OPTHhttps://doaj.org/toc/1177-5483Mike Taylor,1 George Ousler,2 Gail Torkildsen,3 Claire Walshe,1 Matthew C T Fyfe,1 Adele Rowley,1 Steve Webber,1 John D Sheppard,4 Ajay Duggal1 1TopiVert Pharma Limited, London, UK; 2Ora Inc., Andover, MA, USA; 3Andover Eye Associates, Andover, MA, USA; 4Virginia Eye Consultants, Norfolk, VA, USA 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© 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®). After a -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. Keywords: dry eye, DED, TOP1630, ocular inflammationTaylor MOusler GTorkildsen GWalshe CFyfe MCTRowley AWebber SSheppard JDDuggal ADove Medical PressarticleDry EyeDEDTOP1630Ocular InflammationOphthalmologyRE1-994ENClinical Ophthalmology, Vol Volume 13, Pp 261-275 (2019) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Dry Eye DED TOP1630 Ocular Inflammation Ophthalmology RE1-994 |
| spellingShingle |
Dry Eye DED TOP1630 Ocular Inflammation Ophthalmology RE1-994 Taylor M Ousler G Torkildsen G Walshe C Fyfe MCT Rowley A Webber S Sheppard JD Duggal A A phase 2 randomized, double-masked, placebo-controlled study of novel nonsystemic kinase inhibitor TOP1630 for the treatment of dry eye disease |
| description |
Mike Taylor,1 George Ousler,2 Gail Torkildsen,3 Claire Walshe,1 Matthew C T Fyfe,1 Adele Rowley,1 Steve Webber,1 John D Sheppard,4 Ajay Duggal1 1TopiVert Pharma Limited, London, UK; 2Ora Inc., Andover, MA, USA; 3Andover Eye Associates, Andover, MA, USA; 4Virginia Eye Consultants, Norfolk, VA, USA 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© 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®). After a -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. Keywords: dry eye, DED, TOP1630, ocular inflammation |
| format |
article |
| author |
Taylor M Ousler G Torkildsen G Walshe C Fyfe MCT Rowley A Webber S Sheppard JD Duggal A |
| author_facet |
Taylor M Ousler G Torkildsen G Walshe C Fyfe MCT Rowley A Webber S Sheppard JD Duggal A |
| author_sort |
Taylor M |
| title |
A phase 2 randomized, double-masked, placebo-controlled study of novel nonsystemic kinase inhibitor TOP1630 for the treatment of dry eye disease |
| title_short |
A phase 2 randomized, double-masked, placebo-controlled study of novel nonsystemic kinase inhibitor TOP1630 for the treatment of dry eye disease |
| title_full |
A phase 2 randomized, double-masked, placebo-controlled study of novel nonsystemic kinase inhibitor TOP1630 for the treatment of dry eye disease |
| title_fullStr |
A phase 2 randomized, double-masked, placebo-controlled study of novel nonsystemic kinase inhibitor TOP1630 for the treatment of dry eye disease |
| title_full_unstemmed |
A phase 2 randomized, double-masked, placebo-controlled study of novel nonsystemic kinase inhibitor TOP1630 for the treatment of dry eye disease |
| title_sort |
phase 2 randomized, double-masked, placebo-controlled study of novel nonsystemic kinase inhibitor top1630 for the treatment of dry eye disease |
| publisher |
Dove Medical Press |
| publishDate |
2019 |
| url |
https://doaj.org/article/a6447234955b44e08b83b58e5c0fbf7c |
| work_keys_str_mv |
AT taylorm aphase2randomizeddoublemaskedplacebocontrolledstudyofnovelnonsystemickinaseinhibitortop1630forthetreatmentofdryeyedisease AT ouslerg aphase2randomizeddoublemaskedplacebocontrolledstudyofnovelnonsystemickinaseinhibitortop1630forthetreatmentofdryeyedisease AT torkildseng aphase2randomizeddoublemaskedplacebocontrolledstudyofnovelnonsystemickinaseinhibitortop1630forthetreatmentofdryeyedisease AT walshec aphase2randomizeddoublemaskedplacebocontrolledstudyofnovelnonsystemickinaseinhibitortop1630forthetreatmentofdryeyedisease AT fyfemct aphase2randomizeddoublemaskedplacebocontrolledstudyofnovelnonsystemickinaseinhibitortop1630forthetreatmentofdryeyedisease AT rowleya aphase2randomizeddoublemaskedplacebocontrolledstudyofnovelnonsystemickinaseinhibitortop1630forthetreatmentofdryeyedisease AT webbers aphase2randomizeddoublemaskedplacebocontrolledstudyofnovelnonsystemickinaseinhibitortop1630forthetreatmentofdryeyedisease AT sheppardjd aphase2randomizeddoublemaskedplacebocontrolledstudyofnovelnonsystemickinaseinhibitortop1630forthetreatmentofdryeyedisease AT duggala aphase2randomizeddoublemaskedplacebocontrolledstudyofnovelnonsystemickinaseinhibitortop1630forthetreatmentofdryeyedisease AT taylorm phase2randomizeddoublemaskedplacebocontrolledstudyofnovelnonsystemickinaseinhibitortop1630forthetreatmentofdryeyedisease AT ouslerg phase2randomizeddoublemaskedplacebocontrolledstudyofnovelnonsystemickinaseinhibitortop1630forthetreatmentofdryeyedisease AT torkildseng phase2randomizeddoublemaskedplacebocontrolledstudyofnovelnonsystemickinaseinhibitortop1630forthetreatmentofdryeyedisease AT walshec phase2randomizeddoublemaskedplacebocontrolledstudyofnovelnonsystemickinaseinhibitortop1630forthetreatmentofdryeyedisease AT fyfemct phase2randomizeddoublemaskedplacebocontrolledstudyofnovelnonsystemickinaseinhibitortop1630forthetreatmentofdryeyedisease AT rowleya phase2randomizeddoublemaskedplacebocontrolledstudyofnovelnonsystemickinaseinhibitortop1630forthetreatmentofdryeyedisease AT webbers phase2randomizeddoublemaskedplacebocontrolledstudyofnovelnonsystemickinaseinhibitortop1630forthetreatmentofdryeyedisease AT sheppardjd phase2randomizeddoublemaskedplacebocontrolledstudyofnovelnonsystemickinaseinhibitortop1630forthetreatmentofdryeyedisease AT duggala phase2randomizeddoublemaskedplacebocontrolledstudyofnovelnonsystemickinaseinhibitortop1630forthetreatmentofdryeyedisease |
| _version_ |
1718403336450867200 |