Safety of Single-Dose Primaquine in G6PD-Deficient and G6PD-Normal Males in Mali Without Malaria: An Open-Label, Phase 1, Dose-Adjustment Trial

Ingrid Chen, Halimatou Diawara, Almahamoudou Mahamar, Koualy Sanogo, Sekouba Keita, Daouda Kone, Kalifa Diarra, Mousse Djimde, Mohamed Keita, Joelle Brown, Michelle E. Roh, Jimee Hwang, Helmi Pett, Maxwell Murphy, Mikko Niemi, Bryan Greenhouse, Teun Bousema, Roly Gosling, Alassane Dicko

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Methods: We conducted an open-label, nonrandomized, dose-adjustment trial of the safety of 3 single doses of primaquine in glucose-6-phosphate dehydrogenase (G6PD)-deficient adult males in Mali, followed by an assessment of safety in G6PD-deficient boys aged 11–17 years and those aged 5–10 years, including G6PD-normal control groups. The primary outcome was the greatest within-person percentage drop in hemoglobin concentration within 10 days after treatment. Results: Fifty-one participants were included in analysis. G6PD-deficient adult males received 0.40, 0.45, or 0.50 mg/kg of SLD-PQ. G6PD-deficient boys received 0.40 mg/kg of SLD-PQ. There was no evidence of symptomatic hemolysis, and adverse events considered related to study drug (n = 4) were mild. The mean largest within-person percentage change in hemoglobin level between days 0 and 10 was −9.7% (95% confidence interval [CI], −13.5% to −5.90%) in G6PD-deficient adults receiving 0.50 mg/kg of SLD-PQ, −11.5% (95% CI, −16.1% to −6.96%) in G6PD-deficient boys aged 11–17 years, and −9.61% (95% CI, −7.59% to −13.9%) in G6PD-deficient boys aged 5–10 years. The lowest hemoglobin concentration at any point during the study was 92 g/L. Conclusion: SLD-PQ doses between 0.40 and 0.50 mg/kg were well tolerated in G6PD-deficient males in Mali.
Original languageEnglish
JournalJournal of Infectious Diseases
Volume217
Issue number8
Pages (from-to)1298-1308
Number of pages11
ISSN0022-1899
DOIs
Publication statusPublished - 15 Apr 2018
MoE publication typeA1 Journal article-refereed

Fields of Science

  • Primaquine
  • Plasmodium falciparum
  • malaria
  • transmission
  • G6PD deficiency
  • drug safety
  • hemolysis
  • mass drug administration
  • PLASMODIUM-FALCIPARUM MALARIA
  • RANDOMIZED CONTROLLED-TRIAL
  • DEFICIENCY
  • TRANSMISSION
  • HEMOLYSIS
  • EFFICACY
  • AFRICA
  • 3121 Internal medicine

Cite this

Chen, I., Diawara, H., Mahamar, A., Sanogo, K., Keita, S., Kone, D., Diarra, K., Djimde, M., Keita, M., Brown, J., Roh, M. E., Hwang, J., Pett, H., Murphy, M., Niemi, M., Greenhouse, B., Bousema, T., Gosling, R., & Dicko, A. (2018). Safety of Single-Dose Primaquine in G6PD-Deficient and G6PD-Normal Males in Mali Without Malaria: An Open-Label, Phase 1, Dose-Adjustment Trial. Journal of Infectious Diseases, 217(8), 1298-1308. https://doi.org/10.1093/infdis/jiy014