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Phase 1B study of the safety and tolerability of the mineralocorticoid fludrocortisone acetate in patients with geographical atrophy
OBJECTIVE: To evaluate the safety and tolerability of a mineralocorticoid, in a single-dose intravitreal (IVT) injection of 1 mg/0.1 mL and 2 mg/0.1 mL fludrocortisone acetate (FCA) in subjects with geographical atrophy (GA) secondary to age-related macular degeneration. METHODS AND ANALYSIS: This p...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9252207/ https://www.ncbi.nlm.nih.gov/pubmed/36161841 http://dx.doi.org/10.1136/bmjophth-2022-001032 |
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author | Hong, Thomas Chang, Andrew Maddess, Ted Provis, Jan Penfold, Philip |
author_facet | Hong, Thomas Chang, Andrew Maddess, Ted Provis, Jan Penfold, Philip |
author_sort | Hong, Thomas |
collection | PubMed |
description | OBJECTIVE: To evaluate the safety and tolerability of a mineralocorticoid, in a single-dose intravitreal (IVT) injection of 1 mg/0.1 mL and 2 mg/0.1 mL fludrocortisone acetate (FCA) in subjects with geographical atrophy (GA) secondary to age-related macular degeneration. METHODS AND ANALYSIS: This phase 1b study was a two-part dose-escalation prospective study. Part 1 involved a single participant treated with 1 mg/0.1 mL and monitored up to 28 days before being reviewed by a safety review committee. Two subsequent participants were then dosed with the same dose. Part 2 involved a single participant dosed with 2 mg/0.1 mL and monitored up to 28 days when a further five participants were dosed. All participants were followed up for 6 months after baseline. A full ophthalmic assessment was performed at study visits which included GA area, best-corrected visual acuity (BCVA), low-luminance BCVA (LL-BCVA) and intraocular pressure (IOP). Adverse events (AEs) were reported from the first dose of FCA until the end-of-study visit. RESULTS: There were no serious AEs (ocular or systemic) observed with IVT FCA at either 1 mg/0.1 mL or 2 mg/0.1 mL among nine participants. There was no evidence of increased IOP or cataract development. Neither BCVA or LL-BCVA changed significantly in the study-eye over the follow-up period (p=0.28 and 0.38, respectively). Mean GA area increased in the study (0.5 mm(2), p=0.003) and fellow-eyes (0.62 mm(2), p=0.02) over 6 months. Differences between eyes were not significant (p=0.64), and at the lower end of population norms. CONCLUSION: IVT FCA is clinically safe and well tolerated and did not increase IOP. |
format | Online Article Text |
id | pubmed-9252207 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-92522072022-07-05 Phase 1B study of the safety and tolerability of the mineralocorticoid fludrocortisone acetate in patients with geographical atrophy Hong, Thomas Chang, Andrew Maddess, Ted Provis, Jan Penfold, Philip BMJ Open Ophthalmol Retina OBJECTIVE: To evaluate the safety and tolerability of a mineralocorticoid, in a single-dose intravitreal (IVT) injection of 1 mg/0.1 mL and 2 mg/0.1 mL fludrocortisone acetate (FCA) in subjects with geographical atrophy (GA) secondary to age-related macular degeneration. METHODS AND ANALYSIS: This phase 1b study was a two-part dose-escalation prospective study. Part 1 involved a single participant treated with 1 mg/0.1 mL and monitored up to 28 days before being reviewed by a safety review committee. Two subsequent participants were then dosed with the same dose. Part 2 involved a single participant dosed with 2 mg/0.1 mL and monitored up to 28 days when a further five participants were dosed. All participants were followed up for 6 months after baseline. A full ophthalmic assessment was performed at study visits which included GA area, best-corrected visual acuity (BCVA), low-luminance BCVA (LL-BCVA) and intraocular pressure (IOP). Adverse events (AEs) were reported from the first dose of FCA until the end-of-study visit. RESULTS: There were no serious AEs (ocular or systemic) observed with IVT FCA at either 1 mg/0.1 mL or 2 mg/0.1 mL among nine participants. There was no evidence of increased IOP or cataract development. Neither BCVA or LL-BCVA changed significantly in the study-eye over the follow-up period (p=0.28 and 0.38, respectively). Mean GA area increased in the study (0.5 mm(2), p=0.003) and fellow-eyes (0.62 mm(2), p=0.02) over 6 months. Differences between eyes were not significant (p=0.64), and at the lower end of population norms. CONCLUSION: IVT FCA is clinically safe and well tolerated and did not increase IOP. BMJ Publishing Group 2022-07-01 /pmc/articles/PMC9252207/ /pubmed/36161841 http://dx.doi.org/10.1136/bmjophth-2022-001032 Text en © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Retina Hong, Thomas Chang, Andrew Maddess, Ted Provis, Jan Penfold, Philip Phase 1B study of the safety and tolerability of the mineralocorticoid fludrocortisone acetate in patients with geographical atrophy |
title | Phase 1B study of the safety and tolerability of the mineralocorticoid fludrocortisone acetate in patients with geographical atrophy |
title_full | Phase 1B study of the safety and tolerability of the mineralocorticoid fludrocortisone acetate in patients with geographical atrophy |
title_fullStr | Phase 1B study of the safety and tolerability of the mineralocorticoid fludrocortisone acetate in patients with geographical atrophy |
title_full_unstemmed | Phase 1B study of the safety and tolerability of the mineralocorticoid fludrocortisone acetate in patients with geographical atrophy |
title_short | Phase 1B study of the safety and tolerability of the mineralocorticoid fludrocortisone acetate in patients with geographical atrophy |
title_sort | phase 1b study of the safety and tolerability of the mineralocorticoid fludrocortisone acetate in patients with geographical atrophy |
topic | Retina |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9252207/ https://www.ncbi.nlm.nih.gov/pubmed/36161841 http://dx.doi.org/10.1136/bmjophth-2022-001032 |
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