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

Makoto Araie, Baldo Scassellati Sforzolini, Jason Vittitow, Robert N Weinreb, Makoto Araie, Baldo Scassellati Sforzolini, Jason Vittitow, Robert N Weinreb

Abstract

Introduction: Latanoprostene 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.

Methods: This 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.

Results: The 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.

Conclusion: Latanoprostene 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 registration: Clinicaltrials.gov identifier NCT01895985.

Funding: Bausch & Lomb, Inc.

Keywords: Diurnal; Glaucoma; Intraocular pressure; Nitric oxide; Nocturnal; Prostaglandin.

Figures

Fig. 1
Fig. 1
Schematic of the clinical study design. Three study visits were required for all subjects to complete the study. Measurements of intraocular pressure (IOP) were recorded from both eyes for each subject at Visit 2 and Visit 3 at nine time points (8 PM, 10 PM, 12 AM, 2 AM, 4 AM, 8 AM, 10 AM, 12 PM, and 4 PM). Latanoprostene bunod 0.024% was provided to all subjects following the 4 PM IOP assessments at Visit 2, with instructions to instill the study drug QD at 8 PM
Fig. 2
Fig. 2
Mean intraocular pressure (IOP) over 24 h at baseline and after 2 weeks of treatment with latanoprostene bunod, 0.024% in the study eye (a), and the treated fellow eye (b)
Fig. 3
Fig. 3
Change from baseline in mean intraocular pressure (IOP) over 24 h after 2 weeks of treatment with latanoprostene bunod, 0.024%. The mean change from baseline (CFB) ± standard error (mmHg) for the study eye and the treated fellow eye are depicted. Statistically significant differences were observed at all measured time points over the 24-h monitoring period for the CFB in mean IOP assessments in both eyes (P < 0.0001; paired t test)

References

    1. Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA. 2014;311(18):1901–1911. doi: 10.1001/jama.2014.3192.
    1. Weinreb RN, Khaw PT. Primary open-angle glaucoma. Lancet. 2004;363(9422):1711–1720. doi: 10.1016/S0140-6736(04)16257-0.
    1. Iwase A, Suzuki Y, Araie M, et al. The prevalence of primary open-angle glaucoma in Japanese: the Tajimi Study. Ophthalmology. 2004;111(9):1641–1648.
    1. Sommer A, Tielsch JM, Katz J, et al. Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans: the Baltimore eye survey. Arch Ophthalmol. 1991;109(8):1090–1095. doi: 10.1001/archopht.1991.01080080050026.
    1. Anderson DR. Collaborative normal tension glaucoma study. Curr Opin Ophthalmol. 2003;14(2):86–90. doi: 10.1097/00055735-200304000-00006.
    1. Collaborative Normal-Tension Glaucoma Study Group Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Am J Ophthalmol. 1998;126(4):487–497. doi: 10.1016/S0002-9394(98)00223-2.
    1. Deokule S, Weinreb RN. Relationships among systemic blood pressure, intraocular pressure, and open-angle glaucoma. Can J Ophthalmol. 2008;43(3):302–307. doi: 10.3129/i08-061.
    1. Hayreh SS, Zimmerman MB, Podhajsky P, Alward WL. Nocturnal arterial hypotension and its role in optic nerve head and ocular ischemic disorders. Am J Ophthalmol. 1994;117(5):603–624. doi: 10.1016/S0002-9394(14)70067-4.
    1. Meyer JH, Brandi-Dohrn J, Funk J. Twenty four hour blood pressure monitoring in normal tension glaucoma. Br J Ophthalmol. 1996;80(10):864–867. doi: 10.1136/bjo.80.10.864.
    1. Quaranta L, Katsanos A, Russo A, Riva I. 24-hour intraocular pressure and ocular perfusion pressure in glaucoma. Surv Ophthalmol. 2013;58(1):26–41. doi: 10.1016/j.survophthal.2012.05.003.
    1. Gabelt BT, Kaufman PL. Prostaglandin F2 alpha increases uveoscleral outflow in the cynomolgus monkey. Exp Eye Res. 1989;49(3):389–402. doi: 10.1016/0014-4835(89)90049-3.
    1. Lindsey JD, Kashiwagi K, Kashiwagi F, Weinreb RN. Prostaglandins alter extracellular matrix adjacent to human ciliary muscle cells in vitro. Invest Ophthalmol Vis Sci. 1997;38(11):2214–2223.
    1. Lutjen-Drecoll E, Tamm E. Morphological study of the anterior segment of cynomolgus monkey eyes following treatment with prostaglandin F2 alpha. Exp Eye Res. 1988;47(5):761–769. doi: 10.1016/0014-4835(88)90043-7.
    1. Nilsson SF, Samuelsson M, Bill A, Stjernschantz J. Increased uveoscleral outflow as a possible mechanism of ocular hypotension caused by prostaglandin F 2α-1-isopropylester in the cynomolgus monkey. Exp Eye Res. 1989;48(5):707–716. doi: 10.1016/0014-4835(89)90011-0.
    1. Richter M, Krauss AH, Woodward DF, Lutjen-Drecoll E. Morphological changes in the anterior eye segment after long-term treatment with different receptor selective prostaglandin agonists and a prostamide. Invest Ophthalmol Vis Sci. 2003;44(10):4419–4426. doi: 10.1167/iovs.02-1281.
    1. Chuman H, Chuman T, Nao-i N, Sawada A. The effect of l-arginine on intraocular pressure in the human eye. Curr Eye Res. 2000;20(6):511–516. doi: 10.1076/0271-3683(200006)2061-YFT511.
    1. Kotikoski H, Alajuuma P, Moilanen E, et al. Comparison of nitric oxide donors in lowering intraocular pressure in rabbits: role of cyclic GMP. J Ocul Pharmacol Ther. 2002;18(1):11–23. doi: 10.1089/108076802317233171.
    1. Nathanson JA. Nitrovasodilators as a new class of ocular hypotensive agents. J Pharmacol Exp Ther. 1992;260(3):956–965.
    1. Schuman JS, Erickson K, Nathanson JA. Nitrovasodilator effects on intraocular pressure and outflow facility in monkeys. Exp Eye Res. 1994;58(1):99–105. doi: 10.1006/exer.1994.1199.
    1. Stamer WD, Lei Y, Boussommier-Calleja A, Overby DR, Ethier CR. eNOS, a pressure-dependent regulator of intraocular pressure. Invest Ophthalmol Vis Sci. 2011;52(13):9438–9444. doi: 10.1167/iovs.11-7839.
    1. Wizemann AJ, Wizemann V. Organic nitrate therapy in glaucoma. Am J Ophthalmol. 1980;90(1):106–109. doi: 10.1016/S0002-9394(14)75085-8.
    1. Doganay S, Evereklioglu C, Turkoz Y, Er H. Decreased nitric oxide production in primary open-angle glaucoma. Eur J Ophthalmol. 2002;12(1):44–48.
    1. Galassi F, Renieri G, Sodi A, Ucci F, Vannozzi L, Masini E. Nitric oxide proxies and ocular perfusion pressure in primary open angle glaucoma. Br J Ophthalmol. 2004;88(6):757–760. doi: 10.1136/bjo.2003.028357.
    1. Heyne GW, Kiland JA, Kaufman PL, Gabelt BT. Effect of nitric oxide on anterior segment physiology in monkeys. Invest Ophthalmol Vis Sci. 2013;54(7):5103–5110. doi: 10.1167/iovs.12-11491.
    1. Kee C, Kaufman PL, Gabelt BT. Effect of 8-Br cGMP on aqueous humor dynamics in monkeys. Invest Ophthalmol Vis Sci. 1994;35(6):2769–2773.
    1. Kotikoski H, Vapaatalo H, Oksala O. Nitric oxide and cyclic GMP enhance aqueous humor outflow facility in rabbits. Curr Eye Res. 2003;26(2):119–123. doi: 10.1076/ceyr.26.2.119.14511.
    1. Wiederholt M, Sturm A, Lepple-Wienhues A. Relaxation of trabecular meshwork and ciliary muscle by release of nitric oxide. Invest Ophthalmol Vis Sci. 1994;35(5):2515–2520.
    1. Ellis DZ, Dismuke WM, Chokshi BM. Characterization of soluble guanylate cyclase in NO-induced increases in aqueous humor outflow facility and in the trabecular meshwork. Invest Ophthalmol Vis Sci. 2009;50(4):1808–1813. doi: 10.1167/iovs.08-2750.
    1. Schneemann A, Dijkstra BG, van den Berg TJ, Kamphuis W, Hoyng PF. Nitric oxide/guanylate cyclase pathways and flow in anterior segment perfusion. Graefes Arch Clin Exp Ophthalmol. 2002;240(11):936–941. doi: 10.1007/s00417-002-0559-7.
    1. Cavet ME, Vittitow JL, Impagnatiello F, Ongini E, Bastia E. Nitric oxide (NO): an emerging target for the treatment of glaucoma. Invest Ophthalmol Vis Sci. 2014;55(8):5005–5015. doi: 10.1167/iovs.14-14515.
    1. Dismuke WM, Mbadugha CC, Ellis DZ. NO-induced regulation of human trabecular meshwork cell volume and aqueous humor outflow facility involve the BKCa ion channel. Am J Physiol Cell Physiol. 2008;294(6):C1378–C1386. doi: 10.1152/ajpcell.00363.2007.
    1. Cavet ME, Vollmer TR, Harrington KL, VanDerMeid K, Richardson ME. Regulation of endothelin-1-induced trabecular meshwork cell contractility by latanoprostene bunod. Invest Ophthalmol Vis Sci. 2015;56(6):4108–4116. doi: 10.1167/iovs.14-16015.
    1. Krauss AH, Impagnatiello F, Toris CB, et al. Ocular hypotensive activity of BOL-303259-X, a nitric oxide donating prostaglandin F2α agonist, in preclinical models. Exp Eye Res. 2011;93(3):250–255. doi: 10.1016/j.exer.2011.03.001.
    1. Weinreb RN, Ong T, Scassellati Sforzolini B, Vittitow JL, Singh K, Kaufman PL. A randomised, controlled comparison of latanoprostene bunod and latanoprost 0.005% in the treatment of ocular hypertension and open angle glaucoma: the VOYAGER study. Br J Ophthalmol. 2014;99(6):738–745. doi: 10.1136/bjophthalmol-2014-305908.
    1. Asrani S, Zeimer R, Wilensky J, Gieser D, Vitale S, Lindenmuth K. Large diurnal fluctuations in intraocular pressure are an independent risk factor in patients with glaucoma. J Glaucoma. 2000;9(2):134–142. doi: 10.1097/00061198-200004000-00002.
    1. Bergea B, Bodin L, Svedbergh B. Impact of intraocular pressure regulation on visual fields in open-angle glaucoma. Ophthalmology. 1999;106(5):997–1004. doi: 10.1016/S0161-6420(99)00523-0.
    1. Caprioli J, Coleman AL. Intraocular pressure fluctuation a risk factor for visual field progression at low intraocular pressures in the advanced glaucoma intervention study. Ophthalmology. 2008;115(7):1123–1129e3. doi: 10.1016/j.ophtha.2007.10.031.
    1. Sakata R, Aihara M, Murata H, et al. Intraocular pressure change over a habitual 24-hour period after changing posture or drinking water and related factors in normal tension glaucoma. Invest Ophthalmol Vis Sci. 2013;54(8):5313–5320. doi: 10.1167/iovs.13-11792.
    1. Koseki N, Araie M, Shirato S, Yamamoto S. Effect of trabeculectomy on visual field performance in central 30 degrees field in progressive normal-tension glaucoma. Ophthalmology. 1997;104(2):197–201. doi: 10.1016/S0161-6420(97)30334-0.
    1. Shigeeda T, Tomidokoro A, Araie M, Koseki N, Yamamoto S. Long-term follow-up of visual field progression after trabeculectomy in progressive normal-tension glaucoma. Ophthalmology. 2002;109(4):766–770. doi: 10.1016/S0161-6420(01)01009-0.
    1. Sommer A, Tielsch JM, Katz J, et al. Relationship between intraocular pressure and primary open-angle glaucoma among white and black Americans. The Baltimore eye survey. Arch Ophthalmol. 1991;109:1090–1095. doi: 10.1001/archopht.1991.01080080050026.
    1. Iwase A, Suzuki Y, Araie M, et al. The prevalence of primary open-angle glaucoma in Japanese: the Tajimi Study. Ophthalmology. 2004;111(9):1641–1648.
    1. Darhad UNM, Fujioka M, Tatsumi Y, Nagai-Kusuhara A, Maeda H, Negi A. Intraocular pressure lowering effect of once daily versus once weekly latanoprost instillation in the same normal individuals. Kobe J Med Sci. 2007;53(6):297–304.
    1. Kawaguchi I, Higashide T, Ohkubo S, Kawaguchi C, Sugiyama K. Comparison of efficacy of four prostaglandin analogues by bilateral treatment in healthy subjects. Jpn J Ophthalmol. 2012;56(4):346–353. doi: 10.1007/s10384-012-0155-2.
    1. Lim KS, Nau CB, O’Byrne MM, et al. Mechanism of action of bimatoprost, latanoprost, and travoprost in healthy subjects. A crossover study. Ophthalmology. 2008;115(5):790–795 e4. doi: 10.1016/j.ophtha.2007.07.002.
    1. Takahashi M, Higashide T, Sakurai M, Sugiyama K. Discrepancy of the intraocular pressure response between fellow eyes in one-eye trials versus bilateral treatment: verification with normal subjects. J Glaucoma. 2008;17(3):169–174. doi: 10.1097/IJG.0b013e318157a16d.
    1. Drance SM, Crichton A, Mills RP. Comparison of the effect of latanoprost 0.005% and timolol 0.5% on the calculated ocular perfusion pressure in patients with normal-tension glaucoma. Am J Ophthalmol. 1998;125(5):585–592. doi: 10.1016/S0002-9394(98)00019-1.
    1. Ishibashi S, Hirose N, Tawara A, Kubota T. Effect of latanoprost on the diurnal variations in the intraocular and ocular perfusion pressure in normal tension glaucoma. J Glaucoma. 2006;15(5):354–357. doi: 10.1097/01.ijg.0000212264.96864.3e.
    1. Kondo N, Sawada A, Yamamoto T, Taniguchi T. Correlation between individual differences in intraocular pressure reduction and outflow facility due to latanoprost in normal-tension glaucoma patients. Jpn J Ophthalmol. 2006;50(1):20–24. doi: 10.1007/s10384-005-0267-z.
    1. Liu CJ, Ko YC, Cheng CY, et al. Changes in intraocular pressure and ocular perfusion pressure after latanoprost 0.005% or brimonidine tartrate 0.2% in normal-tension glaucoma patients. Ophthalmology. 2002;109(12):2241–2247. doi: 10.1016/S0161-6420(02)01247-2.
    1. McKibbin M, Menage MJ. The effect of once-daily latanoprost on intraocular pressure and pulsatile ocular blood flow in normal tension glaucoma. Eye Lond. 1999;13(Pt 1):31–34. doi: 10.1038/eye.1999.6.
    1. Nakamoto K, Yasuda N. Effect of concomitant use of latanoprost and brinzolamide on 24-hour variation of IOP in normal-tension glaucoma. J Glaucoma. 2007;16(4):352–357. doi: 10.1097/IJG.0b013e318033b491.
    1. Rulo AH, Greve EL, Geijssen HC, Hoyng PF. Reduction of intraocular pressure with treatment of latanoprost once daily in patients with normal-pressure glaucoma. Ophthalmology. 1996;103(8):1276–1282. doi: 10.1016/S0161-6420(96)30510-1.
    1. Quaranta L, Pizzolante T, Riva I, Haidich AB, Konstas AG, Stewart WC. Twenty-four-hour intraocular pressure and blood pressure levels with bimatoprost versus latanoprost in patients with normal-tension glaucoma. Br J Ophthalmol. 2008;92(9):1227–1231. doi: 10.1136/bjo.2008.138024.
    1. Tsumura T, Yoshikawa K, Suzumura H, et al. Bimatoprost ophthalmic solution 0.03% lowered intraocular pressure of normal-tension glaucoma with minimal adverse events. Clin Ophthalmol. 2012;6:1547–1552. doi: 10.2147/OPTH.S36628.
    1. Seibold LK, Kahook MY. The diurnal and nocturnal effects of travoprost in normal-tension glaucoma. Clin Ophthalmol. 2014;8:2189–2193. doi: 10.2147/OPTH.S73125.
    1. Mizoue S, Nakano T, Fuse N, Iwase A, Matsumoto S, Yoshikawa K. Travoprost with sofZia(R) preservative system lowered intraocular pressure of Japanese normal tension glaucoma with minimal side effects. Clin Ophthalmol. 2014;8:347–354. doi: 10.2147/OPTH.S57640.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner