A Randomized, Double-Blind, Safety and Tolerability Study to Assess the Ophthalmic and Renal Effects of Tafenoquine 200 mg Weekly versus Placebo for 6 Months in Healthy Volunteers

Abstract

A randomized, double-blind, placebo-controlled study was conducted to assess the effect of tafenoquine, 200 mg weekly for 6 months on ophthalmic and renal safety. This trial was carried out after observations in previous clinical trials that tafenoquine may be associated with the development of corneal deposits and elevations in serum creatinine. In 120 healthy volunteers who received tafenoquine or placebo in a 2:1 randomization, there was no effect on night vision or other ophthalmic indices measured. Persons taking tafenoquine also showed no difference in mean change in glomerular filtration rate (GFR, mL/s/1.73 m(2)) after 6 months of dosing, with a treatment difference of -0.061 (95% confidence interval, -0.168, 0.045), and non-inferiority margin of -0.247 mL/s/1.73 m(2). Tafenoquine was well tolerated over the course of the study. The results of this study showed no clinically significant effects of tafenoquine on ophthalmic or renal function, and support its continued development as an antimalarial drug.

Malaria Chemoprophylaxis for the International Traveler, Current Options and Future Possibilities

“…This finding had no effect on visual acuity and was fully resolved within one year following cessation of therapy (Nasveld et al, 2010). More extensive clinical ophthalmic evaluation of tafenoquine in a subsequent phase 1 safety trial further supports the vortex keratopathy seen with tafenoquine is not clinically significant (Leary et al, 2009). Tafenoquine shows promise as a causal prophylactic drug and is currently being developed for a radical cure indication for P. vivax through a joint collaboration between GlaxoSmithKline and Medicines for Malaria Venture (MMV, 2011).…”

“…In phase I studies of tafenoquine the drug is well tolerated with single doses up to 600mg and with chronic dosing (6 months) at 200mg weekly following a load of 200mg daily for 3 days (Brueckner et al, 1998;Leary et al, 2009) with no dose-limiting adverse events. The most common side effects observed are gastrointestinal, including heartburn, nausea and gas, usually associated with higher (>200mg) dosing.…”

Comparative ophthalmic assessment of patients receiving tafenoquine or chloroquine/primaquine in a randomized clinical trial for Plasmodium vivax malaria radical cure

“…The first study to report ocular safety of TQ was conducted in healthy volunteers receiving TQ 200 mg weekly for 6 months in Bethesda, MD and Chiltern, UK [30], though is not directly comparable to the current study as different macular function tests were used and there were no clinical retinal examinations, only retinal photography. In the 70 subjects receiving TQ available for assessment, there was no effect on night vision (low-contrast visual acuity test, mesopic contrast threshold tests, and scotopic contrast test) compared with 32 subjects receiving placebo [30]. Forward light scatter test and macular functions were also similar between the two groups after 6 months of TQ therapy [30].…”

“…In the 70 subjects receiving TQ available for assessment, there was no effect on night vision (low-contrast visual acuity test, mesopic contrast threshold tests, and scotopic contrast test) compared with 32 subjects receiving placebo [30]. Forward light scatter test and macular functions were also similar between the two groups after 6 months of TQ therapy [30]. Based on digital retinal photographs, retinal abnormalities were noted in one patient in each study arm.…”

Safety, Tolerability, and Compliance with Long-Term Antimalarial Chemoprophylaxis in American Soldiers in Afghanistan

“…Like primaquine, tafenoquine is known to cause hemolysis in G6PD-deficient persons and also requires CYP2D6 metabolic activation; however, because of its otherwise excellent efficacy and tolerability profile, it remains in clinical development by the U.S. Army. 25,26 As costs continue to decline for alternative safe and efficacious medications, such as DM, DHEC, and AP, it may be advantageous to incorporate these drugs as first-line agents. Within the Military Health System, encompassing 9.7 million soldiers and their families, the number of AP and doxycycline prescriptions were stable or increased from 2007 to 2011, whereas MQ prescriptions dropped from 36% to 2%.…”