PMID- 33813559
OWN - NLM
STAT- MEDLINE
DCOM- 20210927
LR  - 20230912
IS  - 1536-481X (Electronic)
IS  - 1057-0829 (Print)
IS  - 1057-0829 (Linking)
VI  - 30
IP  - 6
DP  - 2021 Jun 1
TI  - A Randomized Phase 2 Trial Comparing Omidenepag Isopropyl 0.002% Once and Twice 
      Daily in Subjects With Primary Open-angle Glaucoma or Ocular Hypertension 
      (SPECTRUM-6).
PG  - 473-480
LID - 10.1097/IJG.0000000000001836 [doi]
AB  - PRCIS: No significant difference was found between the intraocular pressure (IOP) 
      lowering of omidenepag isopropyl 0.002% once daily (QD) and twice daily (BID). 
      However, adverse events (AEs) were higher in the BID arm; thus, QD dosing is the 
      preferred dosing frequency for further investigation. PURPOSE: This phase 2, 
      randomized, double-masked, parallel-arm, multicenter study (NCT03858894) was 
      conducted in the United States to examine whether the efficacy and safety of 
      omidenepag isopropyl 0.002% BID dosing was superior to QD dosing in subjects with 
      primary open-angle glaucoma or ocular hypertension. METHODS: Randomized subjects 
      (1:1) received omidenepag isopropyl 0.002% QD (n=50) or BID (n=48) for 6 weeks 
      (after a </=4-week washout period). IOP was measured at 8:00 am, 12:00 pm, and 4:00 
      pm at baseline and weeks 2 and 6. The primary efficacy endpoint was IOP at each 
      timepoint at weeks 2 and 6. AEs were evaluated. RESULTS: Baseline mean diurnal 
      IOP (+/-SD) post washout was 25.4+/-2.9 mm Hg (BID) and 24.6+/-1.9 mm Hg (QD). At weeks 
      2 and 6, clinically significant IOP reductions from baseline were observed for 
      omidenepag isopropyl BID and QD treatments. Least-squares mean (+/-SE) IOP 
      differences (BID versus QD) were not statistically significant (week 2: 0.44+/-0.68 
      to 1.08+/-0.65 mm Hg; week 6: 0.36+/-0.63 to 0.68+/-0.68 mm Hg) at any timepoint (all P 
      > 0.05). AEs were 3-fold greater in the BID arm (41.7%; QD: 14.0%); the most 
      frequently reported AE was conjunctival/ocular hyperemia (BID: 22.9%; QD: 2.0%). 
      Five subjects discontinued omidenepag isopropyl prematurely, 4 of 5 owing to AEs 
      (BID: 4; QD: 0). CONCLUSION: In this study, the benefit-risk profile of 
      omidenepag isopropyl 0.002% QD was more favorable than the benefit-risk profile 
      of BID. This difference was driven by a higher incidence of local tolerability 
      issues in the BID arm.
CI  - Copyright (c) 2021 The Author(s). Published by Wolters Kluwer Health, Inc.
FAU - Olander, Kenneth W
AU  - Olander KW
AD  - University Eye Specialists, Maryville, TN.
FAU - Sato, Michelle A
AU  - Sato MA
AD  - East West Eye Institute, Los Angeles, CA.
FAU - Abrams, Marc A
AU  - Abrams MA
AD  - Abrams Eye Center, Cleveland, OH.
FAU - Jerkins, Gary W
AU  - Jerkins GW
AD  - Advancing Vision Research, Nashville, TN.
FAU - Lu, Fenghe
AU  - Lu F
AD  - Santen Inc., Emeryville, CA.
FAU - Dinh, Phillip
AU  - Dinh P
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 - Chabi, Almira
AU  - Chabi A
AD  - Santen Inc., Emeryville, CA.
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
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Glaucoma
JT  - Journal of glaucoma
JID - 9300903
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Ophthalmic Solutions)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyridines)
RN  - G0G0H52U6K (omidenepag isopropyl)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Antihypertensive Agents/adverse effects
MH  - Double-Blind Method
MH  - *Glaucoma, Open-Angle/drug therapy
MH  - Glycine/adverse effects/analogs & derivatives
MH  - Humans
MH  - Intraocular Pressure
MH  - *Ocular Hypertension/drug therapy
MH  - Ophthalmic Solutions
MH  - Pyrazoles/adverse effects
MH  - Pyridines/adverse effects
MH  - Treatment Outcome
PMC - PMC8171257
COIS- Disclosure: F.L., P.D., N.O-.K., A.C., and N.K.S. are Santen (employee). The 
      remaining authors declare no conflict of interest.
EDAT- 2021/04/05 06:00
MHDA- 2021/09/28 06:00
PMCR- 2021/06/02
CRDT- 2021/04/04 21:00
PHST- 2020/09/08 00:00 [received]
PHST- 2021/02/23 00:00 [accepted]
PHST- 2021/04/05 06:00 [pubmed]
PHST- 2021/09/28 06:00 [medline]
PHST- 2021/04/04 21:00 [entrez]
PHST- 2021/06/02 00:00 [pmc-release]
AID - 00061198-202106000-00004 [pii]
AID - 10.1097/IJG.0000000000001836 [doi]
PST - ppublish
SO  - J Glaucoma. 2021 Jun 1;30(6):473-480. doi: 10.1097/IJG.0000000000001836.