Phase I/II evaluation of the prophylactic antimalarial activity of pafuramidine in healthy volunteers challenged with Plasmodium falciparum sporozoites

Myaing M. Nyunt, Craig Hendrix, Rahul Bakshi, Nirbhay Kumar, Theresa A Shapiro

Research output: Contribution to journalArticle

Abstract

We evaluated the causal prophylactic antimalarial activity of a single oral dose of pafuramidine (DB289), an experimental prodrug of active metabolite DB75, in a randomized, double-blind, placebo-controlled, outpatient study. Sixteen healthy volunteers were dosed and challenged in a single cohort. Subjects were randomly assigned to one of three treatment arms: 100 mg pafuramidine eight days before challenge, 100 mg pafuramidine the day before challenge,or placebo. Challenge was by the bites of Plasmodium falciparum-infected Anopheles gambiae. Malaria developed in 15 persons but did not develop in one person in the day-8 pafuramidine treatment arm. Plasma levels of DB75 were lower than expected, and as intended were too low to provide suppressive prophylaxis at the earliest appearance of erythrocytic parasites. We conclude that a single dose of 100 mg pafuramidine does not adequately protect non-immune individuals against P. falciparum and shows no clinically or statistically significant evidence of causal prophylactic activity.

Original languageEnglish (US)
Pages (from-to)528-535
Number of pages8
JournalAmerican Journal of Tropical Medicine and Hygiene
Volume80
Issue number4
StatePublished - Apr 2009

Fingerprint

Sporozoites
Antimalarials
Plasmodium falciparum
Healthy Volunteers
Placebos
Anopheles gambiae
Prodrugs
Bites and Stings
Malaria
Parasites
Outpatients
pafuramidine
Therapeutics

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases
  • Virology
  • Medicine(all)

Cite this

@article{0a600b0675494342b1e7ef180093fe52,
title = "Phase I/II evaluation of the prophylactic antimalarial activity of pafuramidine in healthy volunteers challenged with Plasmodium falciparum sporozoites",
abstract = "We evaluated the causal prophylactic antimalarial activity of a single oral dose of pafuramidine (DB289), an experimental prodrug of active metabolite DB75, in a randomized, double-blind, placebo-controlled, outpatient study. Sixteen healthy volunteers were dosed and challenged in a single cohort. Subjects were randomly assigned to one of three treatment arms: 100 mg pafuramidine eight days before challenge, 100 mg pafuramidine the day before challenge,or placebo. Challenge was by the bites of Plasmodium falciparum-infected Anopheles gambiae. Malaria developed in 15 persons but did not develop in one person in the day-8 pafuramidine treatment arm. Plasma levels of DB75 were lower than expected, and as intended were too low to provide suppressive prophylaxis at the earliest appearance of erythrocytic parasites. We conclude that a single dose of 100 mg pafuramidine does not adequately protect non-immune individuals against P. falciparum and shows no clinically or statistically significant evidence of causal prophylactic activity.",
author = "Nyunt, {Myaing M.} and Craig Hendrix and Rahul Bakshi and Nirbhay Kumar and Shapiro, {Theresa A}",
year = "2009",
month = "4",
language = "English (US)",
volume = "80",
pages = "528--535",
journal = "American Journal of Tropical Medicine and Hygiene",
issn = "0002-9637",
publisher = "American Society of Tropical Medicine and Hygiene",
number = "4",

}

TY - JOUR

T1 - Phase I/II evaluation of the prophylactic antimalarial activity of pafuramidine in healthy volunteers challenged with Plasmodium falciparum sporozoites

AU - Nyunt, Myaing M.

AU - Hendrix, Craig

AU - Bakshi, Rahul

AU - Kumar, Nirbhay

AU - Shapiro, Theresa A

PY - 2009/4

Y1 - 2009/4

N2 - We evaluated the causal prophylactic antimalarial activity of a single oral dose of pafuramidine (DB289), an experimental prodrug of active metabolite DB75, in a randomized, double-blind, placebo-controlled, outpatient study. Sixteen healthy volunteers were dosed and challenged in a single cohort. Subjects were randomly assigned to one of three treatment arms: 100 mg pafuramidine eight days before challenge, 100 mg pafuramidine the day before challenge,or placebo. Challenge was by the bites of Plasmodium falciparum-infected Anopheles gambiae. Malaria developed in 15 persons but did not develop in one person in the day-8 pafuramidine treatment arm. Plasma levels of DB75 were lower than expected, and as intended were too low to provide suppressive prophylaxis at the earliest appearance of erythrocytic parasites. We conclude that a single dose of 100 mg pafuramidine does not adequately protect non-immune individuals against P. falciparum and shows no clinically or statistically significant evidence of causal prophylactic activity.

AB - We evaluated the causal prophylactic antimalarial activity of a single oral dose of pafuramidine (DB289), an experimental prodrug of active metabolite DB75, in a randomized, double-blind, placebo-controlled, outpatient study. Sixteen healthy volunteers were dosed and challenged in a single cohort. Subjects were randomly assigned to one of three treatment arms: 100 mg pafuramidine eight days before challenge, 100 mg pafuramidine the day before challenge,or placebo. Challenge was by the bites of Plasmodium falciparum-infected Anopheles gambiae. Malaria developed in 15 persons but did not develop in one person in the day-8 pafuramidine treatment arm. Plasma levels of DB75 were lower than expected, and as intended were too low to provide suppressive prophylaxis at the earliest appearance of erythrocytic parasites. We conclude that a single dose of 100 mg pafuramidine does not adequately protect non-immune individuals against P. falciparum and shows no clinically or statistically significant evidence of causal prophylactic activity.

UR - http://www.scopus.com/inward/record.url?scp=65349162100&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=65349162100&partnerID=8YFLogxK

M3 - Article

VL - 80

SP - 528

EP - 535

JO - American Journal of Tropical Medicine and Hygiene

JF - American Journal of Tropical Medicine and Hygiene

SN - 0002-9637

IS - 4

ER -