Randomized Placebo-Controlled Trial Evaluating the Ophthalmic Safety of Single-Dose Tafenoquine in Healthy Volunteers.
Publication/Presentation Date
9-1-2019
Abstract
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).
Volume
42
Issue
9
First Page
1103
Last Page
1114
ISSN
1179-1942
Published In/Presented At
Ackert, J., Mohamed, K., Slakter, J. S., El-Harazi, S., Berni, A., Gevorkyan, H., Hardaker, E., Hussaini, A., Jones, S. W., Koh, G. C. K. W., Patel, J., Rasmussen, S., Kelly, D. S., Barañano, D. E., Thompson, J. T., Warren, K. A., Sergott, R. C., Tonkyn, J., Wolstenholme, A., Coleman, H., … Green, J. A. (2019). Randomized Placebo-Controlled Trial Evaluating the Ophthalmic Safety of Single-Dose Tafenoquine in Healthy Volunteers. Drug safety, 42(9), 1103–1114. https://doi.org/10.1007/s40264-019-00839-w
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
31187437
Department(s)
Administration and Leadership
Document Type
Article