Evaluation of the Effect of Latanoprostene Bunod Ophthalmic Solution, 0.024% in Lowering Intraocular Pressure over 24 h in Healthy Japanese Subjects

Abstract

IntroductionLatanoprostene bunod is a novel nitric oxide (NO)-donating prostaglandin F2α receptor agonist in clinical development for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. We evaluated the effect of latanoprostene bunod 0.024% instilled once daily (QD) on lowering IOP over a 24-h period in healthy Japanese subjects following 14 days of treatment.MethodsThis was a single-arm, single-center, open-label clinical study of 24 healthy Japanese male volunteers. A baseline IOP profile was established in both eyes in the sitting position at 8 PM, 10 PM, 12 AM, 2 AM, 4 AM, 8 AM, 10 AM, 12 PM, and 4 PM using a Goldmann applanation tonometer. Subjects subsequently instilled latanoprostene bunod 0.024% QD at 8 PM for 14 days in both eyes. The absolute and change from baseline in sitting IOP was assessed on day 14.ResultsThe mean (SD) age of the subjects was 26.8 (6.3) years, and mean (SD) baseline IOP was 13.6 (1.3) mmHg in the study eye. Latanoprostene bunod 0.024% instilled QD for 14 days reduced IOP at all the evaluated time points (P < 0.001) with a mean (SD) 24-h reduction of 3.6 (0.8) mmHg or 27% from the baseline in the study eye. Peak and trough IOP lowering occurred at 8 AM and 8 PM (12 and 24 h following instillation) with a mean reduction of 4.2 (1.8) mmHg, or 30%, and 2.8 (2.2) mmHg, or 20%, respectively. Punctate keratitis and ocular hyperemia, both mild in severity, were the most common adverse events.ConclusionLatanoprostene bunod ophthalmic solution 0.024%, dosed QD for 14 days, significantly lowered mean IOP in healthy Japanese subjects during the entire 24-h period. Studies of latanoprostene bunod in patients diagnosed with normal tension glaucoma are warranted.Trial RegistrationClinicaltrials.gov identifier NCT01895985.FundingBausch & Lomb, Inc.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-015-0260-y) contains supplementary material, which is available to authorized users.

Latanoprostene bunod ophthalmic solution 0.024%: a new treatment option for open‐angle glaucoma and ocular hypertension

“…Research with LBN to date confirms the measurable clinical benefits resulting from the unique dual mechanism of action. Early phase studies established a robust IOP‐lowering effect in both healthy subjects with low baseline IOP and in individuals with open‐angle glaucoma or ocular hypertension; in the latter group, the reduction from baseline to day 28 in diurnal IOP with LBN was significantly greater than that observed with latanoprost, considered the current standard of care . Further, the noted 1.23 mmHg difference between the LBN and latanoprost treatment groups should be seen as clinically relevant given that every 1 mmHg of IOP‐lowering has been associated with an estimated 10–19 per cent reduction in the risk of progression in patients with glaucoma …”

“…The clinical efficacy and safety of LBN 0.024% in patients with open‐angle glaucoma or ocular hypertension were established in two similarly‐designed, double‐masked, pivotal phase 3 studies, both with an open‐label safety extension phase . Additional supportive studies included a one‐year open label phase 3 study, a phase 2 dose‐ranging study versus latanoprost 0.005%, a 24‐hour IOP‐lowering phase 2 study versus timolol maleate 0.5% and a 24‐hour IOP‐lowering phase 1 study in healthy subjects …”

“…The KRONUS study (NCT01895985) was a phase 1, single‐centre, open‐label study that assessed the IOP‐lowering effects of LBN 0.024% once daily in the evening in 24 healthy Japanese male volunteers (mean age 26.8 years, and mean 24‐hour baseline IOP < 14 mmHg) . Significant reductions from baseline in IOP were observed in the 24‐hour IOP profile after 14 days of LBN 0.024% treatment (p < 0.001); the mean (standard deviation) 24‐hour IOP was 10.0 (1.0) mmHg after 14 days of treatment, corresponding to a 27 per cent reduction from baseline in the study eye (mean [standard deviation] reduction of 3.6 [0.8] mmHg).…”

Critical evaluation of latanoprostene bunod in the treatment of glaucoma

“…KRONUS51–53 is the only Phase I trial of LBN performed to date. This trial was performed after dose-finding studies (see “Phase II Trials”; “VOYAGER” sections),54–57 and as such evaluated LBN 0.024%, which previously demonstrated optimal efficacy and safety profile.…”

“…© 2015;99(6):738–745 54. Adapted from Adv Ther , 32, 2015, 1128–1139, Evaluation of the effect of latanoprostene bunod ophthalmic solution, 0.024% in lowering intraocular pressure over 24 h in healthy Japanese subjects Araie M, Sforzolini BS, Vittitow J, Weinreb RN, copyright 2015 51. Data from Weinreb RN, Scassellati Sforzolini B, Vittitow J, Liebmann J. Latanobunod 0.024% versus timolol maleate 0.5% in subjects with open-angle glaucoma or ocular hypertension: the APOLLO Study.…”