Long-term safety of the tafenoquine antimalarial chemoprophylaxis regimen: A 12-month, randomized, double-blind, placebo-controlled trial.

Abstract

BACKGROUND:

Tafenoquine is a long-acting 8-aminoquinoline approved for antimalarial prophylaxis for ≤6 months. Additional data is needed to establish the drug's longer-term safety profile, including potential ophthalmic or neuropsychiatric effects.

METHOD:

This was a randomized, double-blind, placebo-controlled trial in 600 healthy adults. Eligible subjects were randomized 1:1 to receive tafenoquine 200 mg weekly (antimalarial prophylactic regimen) or placebo for 52 weeks. Scheduled safety visits occurred at Weeks 4, 12, 24, 52 (dosing completed), and 64 (final follow-up). Safety assessments included ophthalmic changes, general and neuropsychiatric adverse events (AEs), and laboratory value changes.

RESULTS:

The percentage of subjects with a protocol-defined Serious Ophthalmic Safety Event was lower in the Tafenoquine Group (18.2%) versus the Placebo Group (19%, p = 0.308). There was no significant difference between the percentages of subjects with at least one AE in the Tafenoquine Group (91.0%) versus Placebo (89.9%, p = 0.65). Common AEs seen at a significantly higher incidence for tafenoquine included reversible cornea verticillata (54.5%) and nausea (13.0%), leading to 0.0% and 0.7% discontinuations. Psychiatric AEs occurred at similar percentages in both study groups. Reversible changes in hemoglobin, methemoglobin, creatinine, and blood urea nitrogen (BUN) were noted.

CONCLUSIONS:

This study supports the safety of extended 52-week tafenoquine prophylaxis. CLINICAL TRIAL REGISTRATION NUMBER/CLINICALTRIALS.

GOV IDENTIFIER:

NCT03320174.

• Authors: Anne Novitt-Moreno, Adam Martidis, Victor Gonzalez, Janet Ransom, Charles B Scott, Geoffrey Dow, Mark Reid, Bryan Smith, Victor E Zottig, Lisa Thomas Read, Lindsey S Garver Baldwin, Fred K Chen
• Journal: Travel medicine and infectious disease (Travel Med Infect Dis) 2022 Jan-Feb Vol. 45 Pg. 102211 ISSN: 1873-0442 [Electronic] Netherlands
• PMID: 34801714 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Aminoquinolines
• Antimalarials
• tafenoquine

Topics

• Adult
• Aminoquinolines
• Antimalarials (adverse effects)
• Chemoprevention
• Double-Blind Method
• Humans
• Incidence
• Treatment Outcome