Randomized Placebo-Controlled Trial Evaluating the Ophthalmic Safety of Single-Dose Tafenoquine in Healthy Volunteers
| Autor: | Allen Wolstenholme, Sherif El-Harazi, Jyoti Patel, Scott Rasmussen, John T. Thompson, Justin A. Green, Alex Yuan, Azra Hussaini, Jason S. Slakter, David E. Barañano, Alessandro Berni, Gavin C. K. W. Koh, Elizabeth Hardaker, Deborah S. Kelly, Hakop Gevorkyan, John Tonkyn, Hanna Coleman, Keith A. Warren, Siôn W. Jones, Stephan Duparc, Khadeeja Mohamed, Robert C. Sergott, Jessica Ackert |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
Male medicine.medical_specialty Visual acuity Adolescent Tafenoquine Visual Acuity Placebo-controlled study Administration Oral Toxicology Placebo 030226 pharmacology & pharmacy Retina law.invention Antimalarials Young Adult 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Randomized controlled trial law Internal medicine Clinical endpoint Humans Medicine Single-Blind Method Pharmacology (medical) Original Research Article Prospective Studies 030212 general & internal medicine Prospective cohort study Pharmacology business.industry Optical Imaging Middle Aged Clinical trial chemistry Aminoquinolines Female medicine.symptom business Tomography Optical Coherence |
| Zdroj: | Drug Safety |
| ISSN: | 1179-1942 0114-5916 |
| DOI: | 10.1007/s40264-019-00839-w |
| Popis: | Introduction Tafenoquine has been recently registered for the prevention of relapse in Plasmodium vivax malaria. Objective This study assessed the pharmacodynamic effects of 300-mg single-dose tafenoquine on the retina. Methods This phase I, prospective, multicenter, randomized, single-masked, placebo-controlled, parallel-group study was conducted between 2 February 2016 and 14 September 2017 at three US study centers. Adult healthy volunteers were randomized (2:1) to receive either a single 300-mg oral dose of tafenoquine or matched placebo on day 1. Ophthalmic assessments, including spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF), were conducted at baseline and day 90 and evaluated for pre-determined endpoints by an independent, masked reading center. Results One subject in each group met the composite primary endpoint for retinal changes identified with SD-OCT or FAF, i.e., one out of 306 (0.3%) with tafenoquine, one out of 161 (0.6%) with placebo. Both cases had unilateral focal ellipsoid zone disruption at day 90 with no effect on best-corrected visual acuity. The tafenoquine-treated subject had this abnormality at baseline, and was enrolled in error. There was no difference in ophthalmic safety between tafenoquine and placebo. Conclusion There was no evidence of any pharmacodynamic effect of 300-mg single-dose tafenoquine on the retina or any short-term clinically relevant effects on ophthalmic safety. This clinical trial is registered with ClinicalTrials.gov (identifier: NCT02658435). Electronic supplementary material The online version of this article (10.1007/s40264-019-00839-w) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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