Randomized Placebo-Controlled Trial Evaluating the Ophthalmic Safety of Single-Dose Tafenoquine in Healthy Volunteers.

Autor: Ackert J; Clinical Research and Development, GlaxoSmithKline, Collegeville, PA, USA., Mohamed K; Quantitative Sciences, GlaxoSmithKline Research and Development, Stockley Park West, Uxbridge, Middlesex, UK., Slakter JS; Digital Angiography Reading Center (DARC), Great Neck, New York, NY, USA., El-Harazi S; Lugene Eye Institute, Glendale, CA, USA., Berni A; Global Health, GlaxoSmithKline Research and Development Ltd., Stockley Park West, Uxbridge, Middlesex, UB11 1BT, UK., Gevorkyan H; California Clinical Trials Medical Group in affiliation with Parexel International, Glendale, CA, USA., Hardaker E; Safety Evaluation and Risk Management, GlaxoSmithKline Research and Development, Stockley Park West, Uxbridge, Middlesex, UK., Hussaini A; PAREXEL, Harbor Hospital, Baltimore, Baltimore, MD, USA., Jones SW; Safety Evaluation and Risk Management, GlaxoSmithKline Research and Development, Stockley Park West, Uxbridge, Middlesex, UK., Koh GCKW; Global Health, GlaxoSmithKline Research and Development Ltd., Stockley Park West, Uxbridge, Middlesex, UB11 1BT, UK., Patel J; Clinical Data Management, GlaxoSmithKline Research and Development, Collegeville, PA, USA., Rasmussen S; IQVIA, Overland Park, KS, USA., Kelly DS; Global Clinical Safety and Pharmacovigilance, GlaxoSmithKline, Collegeville, PA, USA., Barañano DE; Retina Specialists, Baltimore, MD, USA., Thompson JT; Retina Specialists, Baltimore, MD, USA., Warren KA; IQVIA, Overland Park, KS, USA., Sergott RC; Neuro-Ophthalmology Service, Wills Eye Hospital, Philadelphia, PA, USA., Tonkyn J; GSK Medicines Research Centre, GlaxoSmithKline, Stevenage, Hertfordshire, UK., Wolstenholme A; GlaxoSmithKline, Upper Providence, Collegeville, PA, USA., Coleman H; Digital Angiography Reading Center (DARC), Great Neck, New York, NY, USA., Yuan A; Digital Angiography Reading Center (DARC), Great Neck, New York, NY, USA., Duparc S; Research and Development, Medicines for Malaria Venture, Geneva, Switzerland., Green JA; Global Health, GlaxoSmithKline Research and Development Ltd., Stockley Park West, Uxbridge, Middlesex, UB11 1BT, UK. justin.a.green@gsk.com.
Jazyk: angličtina
Zdroj: Drug safety [Drug Saf] 2019 Sep; Vol. 42 (9), pp. 1103-1114.
DOI: 10.1007/s40264-019-00839-w
Abstrakt: 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).
Databáze: MEDLINE
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