Randomized Placebo-Controlled Trial Evaluating the Ophthalmic Safety of Single-Dose Tafenoquine in Healthy Volunteers.
Randomized Placebo-Controlled Trial Evaluating the Ophthalmic Safety of Single-Dose Tafenoquine in Healthy Volunteers.
- 2019
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). INTRODUCTION: Tafenoquine has been recently registered for the prevention of relapse in Plasmodium vivax malaria. 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. OBJECTIVE: This study assessed the pharmacodynamic effects of 300-mg single-dose tafenoquine on the retina. 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.
English
0114-5916
10.1007/s40264-019-00839-w [doi] 10.1007/s40264-019-00839-w [pii]
*Aminoquinolines/ad [Administration & Dosage]
*Antimalarials/ad [Administration & Dosage]
*Retina/de [Drug Effects]
*Visual Acuity/de [Drug Effects]
Administration, Oral
Adolescent
Adult
Aminoquinolines/ae [Adverse Effects]
Antimalarials/ae [Adverse Effects]
Female
Humans
Male
Middle Aged
Optical Imaging
Prospective Studies
Single-Blind Method
Tomography, Optical Coherence
Young Adult
MedStar Harbor Hospital
PAREXEL Early Phase Clinical Unit
Journal Article
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). INTRODUCTION: Tafenoquine has been recently registered for the prevention of relapse in Plasmodium vivax malaria. 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. OBJECTIVE: This study assessed the pharmacodynamic effects of 300-mg single-dose tafenoquine on the retina. 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.
English
0114-5916
10.1007/s40264-019-00839-w [doi] 10.1007/s40264-019-00839-w [pii]
*Aminoquinolines/ad [Administration & Dosage]
*Antimalarials/ad [Administration & Dosage]
*Retina/de [Drug Effects]
*Visual Acuity/de [Drug Effects]
Administration, Oral
Adolescent
Adult
Aminoquinolines/ae [Adverse Effects]
Antimalarials/ae [Adverse Effects]
Female
Humans
Male
Middle Aged
Optical Imaging
Prospective Studies
Single-Blind Method
Tomography, Optical Coherence
Young Adult
MedStar Harbor Hospital
PAREXEL Early Phase Clinical Unit
Journal Article