PMID- 20334535
OWN - NLM
STAT- MEDLINE
DCOM- 20110606
LR  - 20220330
IS  - 1557-7732 (Electronic)
IS  - 1080-7683 (Linking)
VI  - 27
IP  - 1
DP  - 2011 Feb
TI  - Safety and pharmacokinetics of a novel lymphocyte function-associated antigen-1 
      antagonist ophthalmic solution (SAR 1118) in healthy adults.
PG  - 99-104
LID - 10.1089/jop.2009.0105 [doi]
AB  - PURPOSE: To investigate the safety, tolerability, and pharmacokinetics (PKs) of 
      topical SAR 1118 Ophthalmic Solution in healthy adults. SAR 1118 is an 
      investigational small molecule lymphocyte function-associated antigen-1 (LFA-1; 
      CD11a/CD18; alphaLbeta2) antagonist that inhibits LFA-1 binding to intercellular 
      adhesion molecule-1 (ICAM-1; CD54) targeting T-cell-mediated inflammation. 
      METHODS: A randomized, double-masked, placebo-controlled, dose-escalation study 
      of SAR 1118 was performed in 4 cohorts with 7 randomized subjects per cohort (2 
      placebo: 5 active drug subjects; 0.1%, 0.3%, 1.0%, 5.0%) in 28 healthy adults. 
      Dosing was divided into 3 periods each separated by a 72-h treatment-free 
      observation: once-daily (QD) x 1, twice-daily (BID) x 10, and thrice-daily (TID) 
      x 10 days. Data obtained at the beginning and end of each period included: 
      slit-lamp, best-corrected visual acuity (BCVA), Schirmer tear test (STT) without 
      anesthesia, tear film break-up time (TBUT), intraocular pressure (IOP), and 
      tear/plasma samples for PK analysis. RESULTS: All subjects completed the study; 
      there were no tolerability issues or missed treatments (total, 1,428 administered 
      doses). No serious ocular or nonocular adverse events (AEs) occurred over 1,148 
      subject study days (41 days/subject) and no significant abnormalities were 
      identified on ocular exam. There were 38 ocular AEs (N = 11 subjects) and 21 
      nonocular AEs (N = 11 subjects). Most AEs were mild in severity and occurred in 
      the 0.3% and placebo groups. No changes were observed in CD3, CD4, and CD8 blood 
      lymphocyte counts. Tear PK profiles support a QD/BID dosing schedule. Plasma 
      levels of SAR 1118 in the 0.1% and 0.3% groups were below level of quantitation 
      (BLQ; <0.50  ng/mL) at all time points and transiently detected within the first 
      5 min to  approximately 1  h following administration in the 1.0% and 5.0% groups. CONCLUSION: 
      SAR 1118 Ophthalmic Solution appears safe and well-tolerated up to 5.0% TID in 
      healthy adult subjects. PK analysis shows adequate ocular exposure with minimal 
      systemic exposure.
FAU - Semba, Charles P
AU  - Semba CP
AD  - SARcode Corporation, San Francisco, California 94104, USA. cpsemba@sarcode.com
FAU - Swearingen, Dennis
AU  - Swearingen D
FAU - Smith, Valerie L
AU  - Smith VL
FAU - Newman, Mary S
AU  - Newman MS
FAU - O'Neill, Charles A
AU  - O'Neill CA
FAU - Burnier, John P
AU  - Burnier JP
FAU - Haughey, David B
AU  - Haughey DB
FAU - Gadek, Thomas R
AU  - Gadek TR
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20100324
PL  - United States
TA  - J Ocul Pharmacol Ther
JT  - Journal of ocular pharmacology and therapeutics : the official journal of the 
      Association for Ocular Pharmacology and Therapeutics
JID - 9511091
RN  - 0 (Lymphocyte Function-Associated Antigen-1)
RN  - 0 (Ophthalmic Solutions)
RN  - 0 (Sulfones)
RN  - 038E5L962W (lifitegrast)
RN  - 47E5O17Y3R (Phenylalanine)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Drug Administration Schedule
MH  - Female
MH  - Humans
MH  - Lymphocyte Function-Associated Antigen-1/*drug effects
MH  - Male
MH  - Middle Aged
MH  - Ophthalmic Solutions
MH  - Phenylalanine/*analogs & derivatives/metabolism/pharmacokinetics
MH  - Prospective Studies
MH  - Sulfones/metabolism/*pharmacokinetics
MH  - Tears/*metabolism
MH  - Young Adult
EDAT- 2010/03/26 06:00
MHDA- 2011/06/07 06:00
CRDT- 2010/03/26 06:00
PHST- 2010/03/26 06:00 [entrez]
PHST- 2010/03/26 06:00 [pubmed]
PHST- 2011/06/07 06:00 [medline]
AID - 10.1089/jop.2009.0105 [doi]
PST - ppublish
SO  - J Ocul Pharmacol Ther. 2011 Feb;27(1):99-104. doi: 10.1089/jop.2009.0105. Epub 
      2010 Mar 24.