TABLE 1. Findings from seven blinded, randomized trials of tafenoquine for prophylaxis and antirelapse treatment of malaria at recommended doses.
| Indication | Year published | Country (Plasmodium species) | Study population characteristics | Study length | Drug regimen | Sample size | Treatment |
|
|---|---|---|---|---|---|---|---|---|
| Outcome | % with outcome (95% CI) | |||||||
| Prophylaxis |
2001* |
Kenya (P. falciparum primarily) |
Semi-immune |
13 wks intervention, follow-up |
TQ 200 mg x 3 days, then weekly |
53 |
Protective efficacy |
86 (73–93) |
| Placebo |
59 |
Reference |
||||||
| 2003† |
Ghana (P. falciparum primarily) |
Semi-immune |
12 wks intervention, 4 wks additional follow-up (double-blind) |
TQ 200 mg x 3 days, then weekly |
91 |
Protective efficacy |
86 (76–92)§ |
|
| MQ 250 mg/wk |
46 |
86 (72–93)§ |
||||||
| Placebo |
94 |
Reference |
||||||
| 2010¶ |
Timor-Leste (P. falciparum and P. vivax) |
Nonimmune |
6 mos intervention, follow-up 20 weeks |
TQ 200 mg x 3 days, then weekly |
492 |
No. of cases (protective efficacy)** |
During intervention: 0 cases; During follow-up: 4 cases [100% (93–100)]†† |
|
| MQ 250 mg/wk |
162 |
During intervention: 0; during follow-up: 1 case [100% (79–100)] |
||||||
| 2018§§ |
Australia (P. falciparum challenge) |
Healthy, nonimmune |
34 days |
TQ 200 mg x 3 days, and 200 mg on day 10 |
12 |
Rescue treatment needed |
0 (0–27)¶¶ |
|
| Placebo |
4 |
100 (40–100) |
||||||
| Antirelapse therapy | 2014*** |
Peru, India, Thailand, Brazil |
≥16 yrs; microscopically confirmed P. vivax monoinfection |
180 days from chloroquine initiation |
CQ x 3 days + TQ 300 mg x 1 |
57 |
Relapse-free efficacy (ITT population) |
89 (77–95)††† |
| CQ x 3 days + PQ 15 mg x 14 days |
50 |
77 (63–87)††† |
||||||
| CQ x 3 days only |
54 |
38 (23–52) |
||||||
| 2019§§§ |
Peru, Brazil, Colombia, Vietnam, Thailand |
≥16 yrs; Hospitalized with microscopically confirmed P. vivax infection |
180 days |
CQ x 3 days + TQ 300 mg x 1 |
166 |
Recurrence-free efficacy (ITT population) |
73 (65–79) |
|
| CQ x 3 days + PQ 15 mg/day x 14 days |
85 |
75 (64–83) |
||||||
| 2019¶¶¶ | Peru, Brazil, Ethiopia, Cambodia, Thailand, Philippines | ≥16 yrs (≥18 in Ethiopia); microscopically confirmed P. vivax infection | 180 days | CQ x 3 days + TQ 300 mg x 1 |
260 |
Recurrence-free efficacy (ITT population) | 62 (55–69)**** |
|
| CQ x 3 days + PQ 15 mg/day x 14 days |
133 |
70 (60–77) |
||||||
| Placebo | 129 | 28 (20–36) | ||||||
Abbreviations: CI = confidence interval; CQ = chloroquine; ITT = intention to treat; MQ = mefloquine; PQ = primaquine; TQ = tafenoquine.
* Shanks GD, Oloo AJ, Aleman GM, et al. A new primaquine analog, tafenoquine (WR 238605), for prophylaxis against Plasmodium falciparum malaria. Clin Infect Dis 2001;33:968–74.
† Hale BR, Owusu-Agyei S, Fryauff DJ, et al. A randomized, double-blind, placebo-controlled, dose-ranging trial of tafenoquine for weekly prophylaxis against Plasmodium falciparum. Clin Infect Dis 2003;36:541–9.
§ Chi squared test (p<0.05).
¶ Nasveld PE, Edstein MD, Reid M, et al. Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects. Antimicrob Agents Chemother 2010;54:792–8.
** Dow GS, McCarthy WF, Reid M, Smith B, Tang D, Shanks GD. A retrospective analysis of the protective efficacy of tafenoquine and mefloquine as prophylactic anti-malarials in non-immune individuals during deployment to an area with endemic malaria area. Malar J 2014;13:49.
†† Fisher exact TQ versus MQ p = 1.0.
§§ McCarthy JS, Smith B, Reid M, et al. Blood schizonticidal activity and safety of tafenoquine when administered as chemoprophylaxis to healthy, non-immune participants followed by blood stage Plasmodium falciparum challenge: a randomized, double-blinded, placebo-controlled Phase 1b study. Clin Infect Dis 2019;69:480–6.
¶¶ Fisher exact p<0.005.
*** Llanos-Cuentas A, Lacerda MV, Rueangweerayut R, et al. Tafenoquine plus chloroquine for the treatment and relapse prevention of Plasmodium vivax malaria (DETECTIVE Phase IIb): a multicentre, double-blind, randomized, phase 2b dose-selection study. Lancet 2014;383:1049–58.
††† Log-rank TQ versus placebo p<0.0001; PQ versus placebo p = 0.0004.
§§§ Llanos-Cuentas A, Lacerda MVG, Hien TT, et al. Tafenoquine versus primaquine to prevent relapse of Plasmodium vivax malaria (GATHER). N Engl J Med 2019;380:229–41.
¶¶¶ Lacerda MVG, Llanos-Cuentas A, Krudsood S, et al. Single-dose tafenoquine to prevent relapse of Plasmodium vivax malaria (DETECTIVE Phase III). N Engl J Med 2019;380:215–28.
**** TQ hazard ratio (HR) 0.3; PQ HR 0.26, p<0.001.