PMID- 31040639
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 1, open-label, single-arm study evaluating the ocular safety of OTX-101 
      and systemic absorption of cyclosporine in healthy human volunteers.
PG  - 591-596
LID - 10.2147/OPTH.S187945 [doi]
AB  - PURPOSE: To evaluate the ocular safety of OTX-101 0.09% - a novel, nanomicellar, 
      clear, aqueous solution of cyclosporine (CsA) - and to determine the systemic 
      exposure to CsA following ophthalmic administration. PATIENTS AND METHODS: 
      Healthy volunteers >/=18 years of age were recruited for participation in this 
      phase 1, open-label, single-center, single-arm, study. Subjects received one drop 
      of OTX-101 0.09% in each eye every 12 hours for 7 days, and once on day 8. Blood 
      samples were collected predose, and 0.25, 0.5, 1, 2, 4, 8, and 12 hours 
      post-first dose on day 1 and day 8. CsA levels in whole blood samples were 
      analyzed using liquid chromatography-tandem mass spectrometry. Pharmacokinetic 
      parameters (maximal whole blood concentration [C(max), ng/mL], time to C(max) 
      [T(max), hours]), and area under the concentration-time curve from 0 to the last 
      measurement [AUC((0-t)), h.ng/mL]) were calculated using noncompartmental 
      analysis. Safety assessments included subject-reported adverse events (AEs), 
      vital signs, visual acuity, intraocular pressure measurement, biomicroscopy, and 
      direct ophthalmoscopy. RESULTS: A total of 16 subjects were enrolled; 15 subjects 
      completed the study. Blood sample analysis indicated limited systemic exposure to 
      CsA; three subjects had a CsA concentration greater than or equal to the lower 
      limit of quantitation (LLOQ) on day 1; only four subjects had three consecutive 
      CsA concentration measurements >/=LLOQ on day 8; the mean+/-SD for C(max) was 
      0.17+/-0.02 ng/mL, T(max) was 1.5+/-0.58 hours, and AUC((0-t)) was 0.53+/-0.06 h.ng/mL. 
      Three subjects reported three AEs (eye pain, eye pruritis, and eye irritation) 
      during the study. No clinically significant changes in the safety assessments 
      were noted. CONCLUSION: The OTX-101 formulation was well tolerated. Systemic 
      exposure to CsA was negligible in healthy volunteers after twice-daily ocular 
      administration. No evidence for systemic accumulation of CsA was observed.
FAU - Karpecki, Paul M
AU  - Karpecki PM
AD  - Kentucky Eye Institute, Lexington, KY, USA, karpecki@karpecki.com.
AD  - Gaddie Eye Centers, Louisville, KY, USA, karpecki@karpecki.com.
FAU - Weiss, Sidney L
AU  - Weiss SL
AD  - i-novion, Inc., Randolph, NJ, USA.
FAU - Kramer, William G
AU  - Kramer WG
AD  - Kramer Consulting, LLC, North Potomac, MD, USA.
FAU - O'Connor, Patrick
AU  - O'Connor P
AD  - Auven Therapeutics, Delray Beach, FL, USA.
FAU - Evans, David
AU  - Evans D
AD  - Total Eye Care, Memphis, TN, USA.
FAU - Johnston, Josh
AU  - Johnston J
AD  - Georgia Eye Partners, Atlanta, GA, USA.
FAU - Jasper, April L
AU  - Jasper AL
AD  - Advanced Eyecare Specialists, West Palm Beach, FL, USA.
FAU - Justice, Angela
AU  - Justice A
AD  - Sun Ophthalmics, Sun Pharmaceutical Industries, Ltd., Princeton, NJ, USA.
FAU - Ogundele, Abayomi B
AU  - Ogundele AB
AD  - Sun Ophthalmics, Sun Pharmaceutical Industries, Ltd., Princeton, NJ, USA.
FAU - Devries, Doug
AU  - Devries D
AD  - Eye Care Associates of Nevada, Sparks, NV, USA.
LA  - eng
PT  - Journal Article
DEP - 20190405
PL  - New Zealand
TA  - Clin Ophthalmol
JT  - Clinical ophthalmology (Auckland, N.Z.)
JID - 101321512
PMC - PMC6454998
OTO - NOTNLM
OT  - cyclosporine
OT  - dry eye disease
OT  - pharmacokinetic
OT  - systemic exposure
COIS- Disclosure This study was sponsored and funded by Ocular Technologies Sarl (now a 
      wholly owned subsidiary of Sun Pharmaceutical Industries, Ltd.), which 
      participated in the design of the study and oversaw its conduct, monitoring, and 
      analysis. Dr Karpecki, and Dr Devries are consultants to Sun Pharmaceutical 
      Industries, Ltd. Angela Justice and Abayomi Ogundele are employees of Sun 
      Pharmaceutical Industries, Ltd. Sidney Weiss was an employee of Ocular 
      Technologies Sarl. Dr Kramer, Dr O'Connor, Dr Evans, Dr Johnston, and Dr Jasper 
      have no financial or proprietary interest in any product, material, or method 
      mentioned. The authors report no other conflicts of interest on this work.
EDAT- 2019/05/02 06:00
MHDA- 2019/05/02 06:01
PMCR- 2019/04/05
CRDT- 2019/05/02 06:00
PHST- 2019/05/02 06:00 [entrez]
PHST- 2019/05/02 06:00 [pubmed]
PHST- 2019/05/02 06:01 [medline]
PHST- 2019/04/05 00:00 [pmc-release]
AID - opth-13-591 [pii]
AID - 10.2147/OPTH.S187945 [doi]
PST - epublish
SO  - Clin Ophthalmol. 2019 Apr 5;13:591-596. doi: 10.2147/OPTH.S187945. eCollection 
      2019.