A Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of 2 and 4 Weeks of Twice-Daily Ocular Trabodenoson in Adults with Ocular Hypertension or Primary Open-Angle Glaucoma

Journal of Ocular Pharmacology and Therapeutics

Volumn 32, Issue 8, 2016, Pages 555-562

  Myers, Jonathan S ^a   Sall, Kenneth N ^b   Dubiner, Harvey ^c   Slomowitz, Natanya ^d   McVicar, William ^d   Rich, Cadmus C ^d   Baumgartner, Rudolf A ^d  

^a WILLS EYE HOSPITAL   (United States)

^b Texan Eye   (United States)

^c Eye Care Centers Management Inc   (United States)

^d INOTEK CORPORATION   (United States)

Author keywords

adenosine; intraocular pressure; ocular hypertension; primary open angle glaucoma; trabecular meshwork; Trabodenoson

Indexed keywords

BIOLOGICAL MARKER; INO 2446; PLACEBO; TRABODENOSON; TROPONIN; UNCLASSIFIED DRUG; NITRIC ACID DERIVATIVE; PURINE DERIVATIVE;

ABNORMAL LABORATORY RESULT; ADULT; AREA UNDER THE CURVE; ARTICLE; BLOOD CELL COUNT; BLOOD CHEMISTRY; CLINICAL EXAMINATION; CLINICAL LABORATORY; COMPARATIVE STUDY; CONJUNCTIVAL HYPEREMIA; CONTROLLED STUDY; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG BLOOD LEVEL; DRUG DISPOSITION; DRUG DISTRIBUTION; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; ELIMINATION HALF-LIFE; EVALUATION STUDY; EYE DISEASE; EYE IRRITATION; EYELID PRURITUS; FEMALE; FOREIGN BODY; GOLDMANN TONOMETRY; HEADACHE; HUMAN; HYPEREMIA; INTRAOCULAR HYPERTENSION; INTRAOCULAR PRESSURE; LABORATORY TEST; MAJOR CLINICAL STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; MIDDLE AGED; MULTICENTER STUDY; OCULAR HYPEREMIA; OPEN ANGLE GLAUCOMA; OROPHARYNX PAIN; PHASE 2 CLINICAL TRIAL; PLASMA HALF LIFE; PRURITUS; RANDOMIZED CONTROLLED TRIAL; SIDE EFFECT; SKIN DISEASE; SKIN PRURITUS; SOFT TISSUE DISEASE; SUBCUTANEOUS TISSUE; SUBCUTANEOUS TISSUE DISORDER; TIME TO MAXIMUM PLASMA CONCENTRATION; TONOMETRY; TOPICAL TREATMENT; TREATMENT DURATION; URINARY TRACT INFECTION; ADOLESCENT; AGED; CHEMISTRY; CLINICAL TRIAL; DRUG TOLERANCE; OCULOPLETHYSMOGRAPHY; PHASE 1 CLINICAL TRIAL; TIME FACTOR; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG TOLERANCE; FEMALE; GLAUCOMA, OPEN-ANGLE; HUMANS; INTRAOCULAR PRESSURE; MALE; MIDDLE AGED; NITRATES; OCULAR HYPERTENSION; PURINES; TIME FACTORS; TONOMETRY, OCULAR; YOUNG ADULT;

EID: 84992213002     PISSN: 10807683     EISSN: 15577732     Source Type: Journal    
DOI: 10.1089/jop.2015.0148     Document Type: Article

References (30)

1. Gordon, M. O., Beiser, J. A., Brandt, J. D., et al. The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch. Ophthalmol. 120:714-720, 2002; discussion 829-830.
2. Kass, M. A., Heuer, D. K., Higginbotham, E. J., et al. The Ocular Hypertension Treatment Study: A randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch. Ophthalmol. 120:701-713, 2002.
3. Leske, M. C., Heijl, A., Hussein, M., et al. Factors for glaucoma progression and the effect of treatment: The early manifest glaucoma trial. Arch. Ophthalmol. 121:48-56, 2003.
4. Heijl, A., Leske, M. C., Bengtsson, B., Hyman, L., Bengtsson, B., and Hussein, M. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch. Ophthalmol. 120:1268-1279, 2002.
5. Schwartz, G. F., Tan, J., and Kotak, S. Hyperemiaassociated costs of medication changes in glaucoma patients treated initially with prostaglandin analogs. J. Ocul. Pharmacol. Ther. 25:555-561, 2009.
6. Alm, A., Grierson, I., and Shields, M. B. Side effects associated with prostaglandin analog therapy. Surv. Ophthalmol. 53 Suppl 1:S93-S105, 2008.
7. Kucukevcilioglu, M., Bayer, A., Uysal, Y., and Altinsoy, H. I. Prostaglandin associated periorbitopathy in patients using bimatoprost, latanoprost and travoprost. Clin. Exp. Ophthal. 42:126-131, 2014.
8. Sanderson, J., Dartt, D. A., Trinkaus-Randall, V., et al. Purines in the eye: recent evidence for the physiological and pathological role of purines in the RPE, retinal neurons, astrocytes, Muller cells, lens, trabecular meshwork, cornea and lacrimal gland. Exp Eye Res. 127:270-279, 2014.
9. Avila, M. Y., Stone, R. A., and Civan, M. M. A(1)-, A(2A)-and A(3)-subtype adenosine receptors modulate intraocular pressure in the mouse. Br. J. Pharmacol. 134:241-245, 2001.
10. Tian, B., Gabelt, B. T., Crosson, C. E., and Kaufman, P. L. Effects of adenosine agonists on intraocular pressure and aqueous humor dynamics in cynomolgus monkeys. Exp. Eye Res. 64:979-989, 1997.
11. Crosson, C. E., and Gray, T. Characterization of ocular hypertension induced by adenosine agonists. Investig. Ophthalmol. Vis. Sci. 37:1833-1839, 1996.
12. Crosson, C. E. Adenosine receptor activation modulates intraocular pressure in rabbits. J. Pharmacol. Exp. Ther. 273:320-326, 1995.
13. Crosson, C. E., and Gray, T. Modulation of intraocular pressure by adenosine agonists. J. Ocul. Pharmacol. 10:379-383, 1994.
14. Crosson, C. E. Ocular hypotensive activity of the adenosine agonist (R)-phenylisopropyladenosine in rabbits. Curr. Eye Res. 11:453-458, 1992.
15. Crosson, C. E., Sloan, C. F., and Yates, P. W. Modulation of conventional outflow facility by the adenosine A1 agonist N6-cyclohexyladenosine. Investig. Ophthalmol. Vis. Sci. 46:3795-3799, 2005.
16. Shearer, T. W., and Crosson, C. E. Adenosine A1 receptor modulation of MMP-2 secretion by trabecular meshwork cells. Investig. Ophthalmol. Vis. Sci. 43:3016-3020, 2002.
17. Zhong, Y., Yang, Z., Huang, W. C., and Luo, X. Adenosine, adenosine receptors and glaucoma: An updated overview. Biochim. Biophys. Acta. 1830:2882-2890, 2013.
18. Bradley, J. M., Kelley, M. J., Zhu, X., Anderssohn, A. M., Alexander, J. P., and Acott, T. S. Effects of mechanical stretching on trabecular matrix metalloproteinases. Investig. Ophthalmol. Vis. Sci. 42:1505-1513, 2001.
19. Bradley, J. M., Vranka, J., Colvis, C. M., et al. Effect of matrix metalloproteinases activity on outflow in perfused human organ culture. Investig. Ophthalmol. Vis. Sci. 39:2649-2658, 1998.
20. Daines, B. S., Kent, A. R., McAleer, M. S., and Crosson, C. E. Intraocular adenosine levels in normal and ocularhypertensive patients. J. Ocul. Pharmacol. Ther. 19:113-119, 2003.
21. Raber, S., Mandema, J. W., Li, H., and Nickens, D. J. A model-based dose-response meta-analysis of ocular hypotensive agents as a drug development tool to evaluate new therapies in glaucoma. J. Ocul. Pharmacol. Ther. 31:189-197, 2015.
22. Toris, C. B., Zhan, G. L., Zhao, J., Camras, C. B., and Yablonski, M. E. Potential mechanism for the additivity of pilocarpine and latanoprost. Am J. Ophthalmol. 131:722-728, 2001.
23. Toris, C. B., Gabelt, B. T., and Kaufman, P. L. Update on the mechanism of action of topical prostaglandins for intraocular pressure reduction. Surv. Ophthalmol. 53 Suppl 1:S107-S120, 2008.
24. Winkler, N. S., and Fautsch, M. P. Effects of prostaglandin analogues on aqueous humor pathways. J. Ocul. Pharmacol. Ther. 30:102-109, 2014.
25. Alm, A. Latanoprost in the treatment of glaucoma. Clin. Ophthalmol. 8:1967-1985, 2014.
26. Lutjen-Drecoll, E., Futa, R., and Rohen, J. W. Ultrahistochemical studies on tangential sections of the trabecular meshwork in normal and glaucomatous eyes. Investig. Ophthalmol. Vis. Sci. 21:563-573, 1981.
27. Tektas, O. Y., and Lutjen-Drecoll, E. Structural changes of the trabecular meshwork in different kinds of glaucoma. Exp. Eye Res. 88:769-775, 2009.
28. Lutjen-Drecoll, E., Rittig, M., Rauterberg, J., Jander, R., and Mollenhauer, J. Immunomicroscopical study of type VI collagen in the trabecular meshwork of normal and glaucomatous eyes. Exp. Eye Res. 48:139-147, 1989.
29. Lu, Z., and Xu, S. ERK1/2 MAP kinases in cell survival and apoptosis. IUBMB Life. 58:621-631, 2006.
30. Joe, M. K., Kwon, H. S., Cojocaru, R., and Tomarev, S. I. Myocilin regulates cell proliferation and survival. J. Biolog. Chem. 289:10155-10167, 2014.