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

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

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.
Alkuperäiskielienglanti
LehtiJournal of Infectious Diseases
Vuosikerta217
Numero8
Sivut1298-1308
Sivumäärä11
ISSN0022-1899
DOI - pysyväislinkit
TilaJulkaistu - 15 huhtikuuta 2018
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Lisätietoja

Erratum: The Journal of Infectious Diseases, Volume 217, Issue 7, 1 April 2018, Page 1171, https://doi.org/10.1093/infdis/jiy074

Tieteenalat

  • 3121 Sisätaudit

Lainaa tätä

Chen, Ingrid ; Diawara, Halimatou ; Mahamar, Almahamoudou ; Sanogo, Koualy ; Keita, Sekouba ; Kone, Daouda ; Diarra, Kalifa ; Djimde, Mousse ; Keita, Mohamed ; Brown, Joelle ; Roh, Michelle E. ; Hwang, Jimee ; Pett, Helmi ; Murphy, Maxwell ; Niemi, Mikko ; Greenhouse, Bryan ; Bousema, Teun ; Gosling, Roly ; Dicko, Alassane. / Safety of Single-Dose Primaquine in G6PD-Deficient and G6PD-Normal Males in Mali Without Malaria : An Open-Label, Phase 1, Dose-Adjustment Trial. Julkaisussa: Journal of Infectious Diseases. 2018 ; Vuosikerta 217, Nro 8. Sivut 1298-1308.
@article{e108d6d0d338418bb4bd575c782201cb,
title = "Safety of Single-Dose Primaquine in G6PD-Deficient and G6PD-Normal Males in Mali Without Malaria: An Open-Label, Phase 1, Dose-Adjustment Trial",
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.",
keywords = "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",
author = "Ingrid Chen and Halimatou Diawara and Almahamoudou Mahamar and Koualy Sanogo and Sekouba Keita and Daouda Kone and Kalifa Diarra and Mousse Djimde and Mohamed Keita and Joelle Brown and Roh, {Michelle E.} and Jimee Hwang and Helmi Pett and Maxwell Murphy and Mikko Niemi and Bryan Greenhouse and Teun Bousema and Roly Gosling and Alassane Dicko",
note = "Erratum: The Journal of Infectious Diseases, Volume 217, Issue 7, 1 April 2018, Page 1171, https://doi.org/10.1093/infdis/jiy074",
year = "2018",
month = "4",
day = "15",
doi = "10.1093/infdis/jiy014",
language = "English",
volume = "217",
pages = "1298--1308",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press USA",
number = "8",

}

Chen, I, Diawara, H, Mahamar, A, Sanogo, K, Keita, S, Kone, D, Diarra, K, Djimde, M, Keita, M, Brown, J, Roh, ME, 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, Vuosikerta 217, Nro 8, Sivut 1298-1308. https://doi.org/10.1093/infdis/jiy014

Safety of Single-Dose Primaquine in G6PD-Deficient and G6PD-Normal Males in Mali Without Malaria : An Open-Label, Phase 1, Dose-Adjustment Trial. / Chen, Ingrid; Diawara, Halimatou; Mahamar, Almahamoudou; Sanogo, Koualy; Keita, Sekouba; Kone, Daouda; Diarra, Kalifa; Djimde, Mousse; Keita, Mohamed; Brown, Joelle; Roh, Michelle E.; Hwang, Jimee; Pett, Helmi; Murphy, Maxwell; Niemi, Mikko; Greenhouse, Bryan; Bousema, Teun; Gosling, Roly; Dicko, Alassane.

julkaisussa: Journal of Infectious Diseases, Vuosikerta 217, Nro 8, 15.04.2018, s. 1298-1308.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - Safety of Single-Dose Primaquine in G6PD-Deficient and G6PD-Normal Males in Mali Without Malaria

T2 - An Open-Label, Phase 1, Dose-Adjustment Trial

AU - Chen, Ingrid

AU - Diawara, Halimatou

AU - Mahamar, Almahamoudou

AU - Sanogo, Koualy

AU - Keita, Sekouba

AU - Kone, Daouda

AU - Diarra, Kalifa

AU - Djimde, Mousse

AU - Keita, Mohamed

AU - Brown, Joelle

AU - Roh, Michelle E.

AU - Hwang, Jimee

AU - Pett, Helmi

AU - Murphy, Maxwell

AU - Niemi, Mikko

AU - Greenhouse, Bryan

AU - Bousema, Teun

AU - Gosling, Roly

AU - Dicko, Alassane

N1 - Erratum: The Journal of Infectious Diseases, Volume 217, Issue 7, 1 April 2018, Page 1171, https://doi.org/10.1093/infdis/jiy074

PY - 2018/4/15

Y1 - 2018/4/15

N2 - 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.

AB - 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.

KW - Primaquine

KW - Plasmodium falciparum

KW - malaria

KW - transmission

KW - G6PD deficiency

KW - drug safety

KW - hemolysis

KW - mass drug administration

KW - PLASMODIUM-FALCIPARUM MALARIA

KW - RANDOMIZED CONTROLLED-TRIAL

KW - DEFICIENCY

KW - TRANSMISSION

KW - HEMOLYSIS

KW - EFFICACY

KW - AFRICA

KW - 3121 Internal medicine

U2 - 10.1093/infdis/jiy014

DO - 10.1093/infdis/jiy014

M3 - Article

VL - 217

SP - 1298

EP - 1308

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 8

ER -