PMID- 34801714
OWN - NLM
STAT- MEDLINE
DCOM- 20220324
LR  - 20220324
IS  - 1873-0442 (Electronic)
IS  - 1477-8939 (Linking)
VI  - 45
DP  - 2022 Jan-Feb
TI  - Long-term safety of the tafenoquine antimalarial chemoprophylaxis regimen: A 
      12-month, randomized, double-blind, placebo-controlled trial.
PG  - 102211
LID - S1477-8939(21)00252-0 [pii]
LID - 10.1016/j.tmaid.2021.102211 [doi]
AB  - 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.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Novitt-Moreno, Anne
AU  - Novitt-Moreno A
AD  - Fast-Track Drugs & Biologics, Poolesville, MD, 20878, USA.
FAU - Martidis, Adam
AU  - Martidis A
AD  - Retina Consultants of Southern Colorado, Colorado Springs, CO, 80909, USA.
FAU - Gonzalez, Victor
AU  - Gonzalez V
AD  - Valley Retina Institute, McAllen, TX, 78503, USA.
FAU - Ransom, Janet
AU  - Ransom J
AD  - Fast-Track Drugs & Biologics, Poolesville, MD, 20878, USA.
FAU - Scott, Charles B
AU  - Scott CB
AD  - Fast-Track Drugs & Biologics, Poolesville, MD, 20878, USA.
FAU - Dow, Geoffrey
AU  - Dow G
AD  - 60 degrees Pharmaceuticals LLC, Washington, DC, 20036, USA. Electronic address: 
      geoffdow@60degreespharma.com.
FAU - Reid, Mark
AU  - Reid M
AD  - Graythan Regulatory Services Pty Ltd, Brisbane, QLD, 4000, Australia.
FAU - Smith, Bryan
AU  - Smith B
AD  - 60 degrees Pharmaceuticals LLC, Washington, DC, 20036, USA.
FAU - Zottig, Victor E
AU  - Zottig VE
AD  - United States Army Medical Materiel Development Activity (USAMMDA), Ft Detrick, 
      MD, 21702, USA.
FAU - Read, Lisa Thomas
AU  - Read LT
AD  - United States Army Medical Materiel Development Activity (USAMMDA), Ft Detrick, 
      MD, 21702, USA.
FAU - Garver Baldwin, Lindsey S
AU  - Garver Baldwin LS
AD  - United States Army Medical Materiel Development Activity (USAMMDA), Ft Detrick, 
      MD, 21702, USA.
FAU - Chen, Fred K
AU  - Chen FK
AD  - Centre for Ophthalmology and Visual Sciences (incorporating Lions Eye Institute), 
      The University of Western Australia, Nedlands, WA, 6009, Australia; Linear 
      Clinical Research, Nedlands, WA, 6009, Australia.
LA  - eng
SI  - ClinicalTrials.gov/NCT03320174
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20211118
PL  - Netherlands
TA  - Travel Med Infect Dis
JT  - Travel medicine and infectious disease
JID - 101230758
RN  - 0 (Aminoquinolines)
RN  - 0 (Antimalarials)
RN  - 262P8GS9L9 (tafenoquine)
SB  - IM
CIN - Travel Med Infect Dis. 2022 Mar-Apr;46:102268. PMID: 35092842
MH  - Adult
MH  - Aminoquinolines
MH  - *Antimalarials/adverse effects
MH  - Chemoprevention
MH  - Double-Blind Method
MH  - Humans
MH  - Incidence
MH  - Treatment Outcome
OTO - NOTNLM
OT  - Cornea
OT  - Malaria
OT  - Neuropsychiatric
OT  - Ophthalmic
OT  - Tafenoquine
OT  - Toxicity
EDAT- 2021/11/22 06:00
MHDA- 2022/03/25 06:00
CRDT- 2021/11/21 20:42
PHST- 2021/10/07 00:00 [received]
PHST- 2021/11/09 00:00 [revised]
PHST- 2021/11/15 00:00 [accepted]
PHST- 2021/11/22 06:00 [pubmed]
PHST- 2022/03/25 06:00 [medline]
PHST- 2021/11/21 20:42 [entrez]
AID - S1477-8939(21)00252-0 [pii]
AID - 10.1016/j.tmaid.2021.102211 [doi]
PST - ppublish
SO  - Travel Med Infect Dis. 2022 Jan-Feb;45:102211. doi: 10.1016/j.tmaid.2021.102211. 
      Epub 2021 Nov 18.