PMID- 30839416
OWN - NLM
STAT- MEDLINE
DCOM- 20200605
LR  - 20200605
IS  - 1536-481X (Electronic)
IS  - 1057-0829 (Linking)
VI  - 28
IP  - 5
DP  - 2019 May
TI  - Phase 2, Randomized, Dose-finding Studies of Omidenepag Isopropyl, a Selective 
      EP2 Agonist, in Patients With Primary Open-angle Glaucoma or Ocular Hypertension.
PG  - 375-385
LID - 10.1097/IJG.0000000000001221 [doi]
AB  - PReCIS:: Three randomized, multicenter studies demonstrated the stable 
      intraocular pressure-lowering effects and tolerability of omidenepag isopropyl in 
      patients with primary open-angle glaucoma and ocular hypertension; 0.002% was 
      identified as the optimal dose for further investigation. PURPOSE: The purpose of 
      this study was to assess the safety and efficacy of omidenepag isopropyl, a 
      selective EP2 agonist, and to determine the optimal dose for further 
      investigation. PATIENTS AND METHODS: Three randomized, controlled, masked, 
      multicenter studies were conducted in United States (study 1, NCT01868126; study 
      2, NCT02179008) and Japan (study 3, NCT02623738). Patients were randomized to 1 
      of 7 omidenepag isopropyl concentrations (0.0003%, 0.001%, 0.0012%, 0.0016%, 
      0.002%, 0.0025%, and 0.003%), latanoprost (0.005%), or placebo, 1 drop once daily 
      for 28 days (studies 1 and 3) or 90 days (study 2). Primary endpoints were the 
      observed mean diurnal intraocular pressure (IOP) and IOP at each time point on 
      the final visit (studies 1 and 2) and change from baseline in mean diurnal IOP at 
      week 4 (study 3). RESULTS: IOP-lowering effects of omidenepag isopropyl 0.0003% 
      to 0.002% increased dose-dependently. Omidenepag isopropyl 0.002% and 0.0025% 
      resulted in clinically relevant mean diurnal IOP reductions from baseline that 
      were similar to those of latanoprost and superior to placebo (P<0.005). Maximum 
      reductions had already been achieved by week 1, and stable IOP-lowering effects 
      were observed at all postbaseline time points up to 3 months. Most adverse events 
      (AEs) were mild. Conjunctival hyperemia was the most frequently reported AE, the 
      incidence of which increased dose-dependently. The safety profiles of omidenepag 
      isopropyl 0.002% and 0.0025% were similar, with a slightly lower incidence of AEs 
      in the 0.002% group. CONCLUSIONS: Omidenepag isopropyl demonstrated stable 
      IOP-lowering effects and was well tolerated; 0.002% was identified as the optimal 
      dose for phase 3 investigation.
FAU - Aihara, Makoto
AU  - Aihara M
AD  - Ophthalmology, University of Tokyo, Bunkyo-ku.
FAU - Lu, Fenghe
AU  - Lu F
AD  - Santen Inc., Emeryville, CA.
FAU - Kawata, Hisashi
AU  - Kawata H
AD  - Santen Pharmaceutical Co., Ltd., Osaka, Japan.
FAU - Iwata, Akihiro
AU  - Iwata A
AD  - Santen Pharmaceutical Co., Ltd., Osaka, Japan.
FAU - Liu, Kathy
AU  - Liu K
AD  - Santen Inc., Emeryville, CA.
FAU - Odani-Kawabata, Noriko
AU  - Odani-Kawabata N
AD  - Santen Inc., Emeryville, CA.
AD  - Santen Pharmaceutical Co., Ltd., Osaka, Japan.
FAU - Shams, Naveed K
AU  - Shams NK
AD  - Santen Inc., Emeryville, CA.
AD  - Santen Pharmaceutical Co., Ltd., Osaka, Japan.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PL  - United States
TA  - J Glaucoma
JT  - Journal of glaucoma
JID - 9300903
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyridines)
RN  - 0 (Receptors, Prostaglandin E, EP2 Subtype)
RN  - G0G0H52U6K (omidenepag isopropyl)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Aged
MH  - Antihypertensive Agents/*administration & dosage
MH  - Corneal Pachymetry
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Glaucoma, Open-Angle/*drug therapy/physiopathology
MH  - Glycine/administration & dosage/*analogs & derivatives
MH  - Humans
MH  - Intraocular Pressure/drug effects
MH  - Male
MH  - Middle Aged
MH  - Ocular Hypertension/drug therapy/physiopathology
MH  - Ophthalmoscopy
MH  - Pyrazoles/*administration & dosage
MH  - Pyridines/*administration & dosage
MH  - Receptors, Prostaglandin E, EP2 Subtype/*agonists
MH  - Slit Lamp Microscopy
MH  - Tonometry, Ocular
EDAT- 2019/03/07 06:00
MHDA- 2020/06/06 06:00
CRDT- 2019/03/07 06:00
PHST- 2019/03/07 06:00 [pubmed]
PHST- 2020/06/06 06:00 [medline]
PHST- 2019/03/07 06:00 [entrez]
AID - 10.1097/IJG.0000000000001221 [doi]
PST - ppublish
SO  - J Glaucoma. 2019 May;28(5):375-385. doi: 10.1097/IJG.0000000000001221.