Document Detail

Safety, tolerability, and bioavailability of topical SAR 1118, a novel antagonist of lymphocyte function-associated antigen-1: a phase 1b study.
MedLine Citation:
PMID:  22538219     Owner:  NLM     Status:  MEDLINE    
PURPOSE: A growing body of evidence points to a role for inflammation mediated by lymphocyte function-associated antigen-1 (LFA-1) and its ligand intercellular adhesion molecule-1 in the pathogenesis of diabetic macular oedema. This phase 1b clinical trial assessed the safety, tolerability, and pharmacokinetics of topically administered SAR 1118, a novel LFA-1 antagonist, in human subjects.
METHODS: In this prospective, randomized, double-masked trial, 13 subjects scheduled for vitrectomy received one of three concentrations of topical SAR 1118 (0.1, 1.0, or 5.0%) twice daily for 1 week before surgery. Undiluted aqueous and vitreous samples were collected at surgery and analysed for the concentration of the medication.
RESULTS: All subjects completed the entire course of medication. The only adverse events reported were instillation site irritation (4/13, 31%) and dysgeusia (3/13, 23%). These were mild and transient, occurring at the highest dose. Mean concentrations (ng/ml) of SAR 1118 in the aqueous humour were 0.25, 37.2, and 101.1 for the 0.1%, 1.0%, and 5.0% dose groups, respectively. SAR 1118 was below the level of detection (0.5 ng/ml) for all vitreous samples except in a single subject who had a history of prior vitrectomy and a dislocated intraocular lens.
CONCLUSIONS: Topical SAR 1118 was safe and well tolerated, and dose-dependent levels of drug were detected in aqueous. However, vitreous levels were below the threshold of detection with the concentrations tested. Further investigation of this medication for posterior segment applications would require intravitreal delivery or chemical modification of the drug.
D M Paskowitz; Q D Nguyen; P Gehlbach; J T Handa; S Solomon; W Stark; O Shaikh; C Semba; T R Gadek; D V Do
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Publication Detail:
Type:  Clinical Trial, Phase I; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2012-04-27
Journal Detail:
Title:  Eye (London, England)     Volume:  26     ISSN:  1476-5454     ISO Abbreviation:  Eye (Lond)     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-07-13     Completed Date:  2012-09-28     Revised Date:  2013-07-02    
Medline Journal Info:
Nlm Unique ID:  8703986     Medline TA:  Eye (Lond)     Country:  England    
Other Details:
Languages:  eng     Pagination:  944-9     Citation Subset:  IM    
Wilmer Eye Institute, Johns Hopkins University, 600 North Wolfe Street, Baltimore, MD 21287, USA.
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MeSH Terms
Aqueous Humor / metabolism
Diabetic Retinopathy / complications
Dose-Response Relationship, Drug
Double-Blind Method
Drug Administration Schedule
Lymphocyte Function-Associated Antigen-1 / drug effects*
Macular Edema / drug therapy*,  etiology,  metabolism
Ophthalmic Solutions
Phenylalanine / adverse effects,  analogs & derivatives*,  pharmacokinetics
Prospective Studies
Receptors, Lymphocyte Homing / antagonists & inhibitors*
Sulfones / adverse effects*,  pharmacokinetics
Vitreous Body / metabolism
Reg. No./Substance:
0/Lymphocyte Function-Associated Antigen-1; 0/Ophthalmic Solutions; 0/Receptors, Lymphocyte Homing; 0/SAR 1118; 0/Sulfones; 63-91-2/Phenylalanine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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