Determination of an optimal dosing regimen for fexinidazole, a novel oral drug for the treatment of human African trypanosomiasis: first-in-human studies

Clinical Pharmacokinetics
Antoine TarralNathalie Strub-Wourgaft


Fexinidazole is a 5-nitroimidazole recently included in a clinical efficacy trial as an oral drug for the treatment of human African trypanosomiasis (HAT). Preclinical studies showed it acts as a pharmacologically active pro-drug with two key active metabolites: sulfoxide and sulfone (the most active metabolite). The present studies aimed to determine the best dose regimen for the treatment of stage 2 sleeping sickness patients, which could eventually also treat stage 1 patients. Fexinidazole was assessed in 154 healthy adult male subjects of sub-Saharan African origin. Three initial first-in-human studies and two additional studies assessed a single ascending dose and multiple ascending doses (both under fasted conditions), tablet versus suspension formulation and food effect (fasted vs. high-fat meal and field-adapted food), and multiple ascending doses with a loading dose regimen under fed conditions. Fexinidazole was well-tolerated in a single dose from 100 to 3,600 mg, with quick absorption of the parent drug and rapid metabolism into sulfoxide [time to maximum concentration (t max) 2-5 h] and sulfone (t max 18-24 h). The tablet formulation was approximately 25 % less bioavailable than the suspension, and food intake incre...Continue Reading


Nov 1, 1992·Clinical Pharmacokinetics·A H LauL H Danziger
Dec 1, 1989·Clinical Pharmacology and Therapeutics·G S HughesA R Euler
Jun 26, 1999·British Journal of Clinical Pharmacology·P RosenzweigS Brohier
Jun 29, 1999·Clinical Pharmacokinetics·K C LampM K Lacy
Jul 10, 2007·British Journal of Pharmacology·Michael P BarrettRichard R Tidwell
Mar 28, 2008·Proceedings of the National Academy of Sciences of the United States of America·Shane R WilkinsonIan Cheeseman
Sep 2, 2008·Journal of Clinical Pharmacology·Marek MalikDavid Madge
Aug 27, 2009·Interdisciplinary Perspectives on Infectious Diseases·Cyrus J Bacchi
Oct 17, 2009·Lancet·Reto BrunChristian Burri
May 5, 2010·Antimicrobial Agents and Chemotherapy·Antoaneta Y SokolovaAlan H Fairlamb
Feb 4, 2012·Science Translational Medicine·Susan WyllieAlan H Fairlamb
Nov 8, 2012·PLoS Neglected Tropical Diseases·Maria Terezinha BahiaIsabela Ribeiro
Dec 29, 2012·PLoS Neglected Tropical Diseases·E HaskerM Boelaert


Sep 29, 2015·Expert Review of Anti-infective Therapy·Amy J Jones, Vicky M Avery
Sep 11, 2014·Expert Review of Anti-infective Therapy·Gilles EperonFrançois Chappuis
Dec 25, 2015·European Journal of Medicinal Chemistry·Avninder S BhambraVladimir Krystof
Nov 26, 2015·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Elissa MeitesKimberly A Workowski
Oct 21, 2014·Tropical Medicine & International Health : TM & IH·P MitashiPascal Lutumba
Jun 5, 2015·PLoS Neglected Tropical Diseases·Mathias BeigPaul M Selzer
Jun 10, 2015·PLoS Neglected Tropical Diseases·Pere SimarroJean G Jannin
Aug 23, 2016·Journal of Medicinal Chemistry·Stephanie RussellMatthew J Piggott
Jan 24, 2019·Antimicrobial Agents and Chemotherapy·James A WatsonNicholas J White
May 17, 2019·The Journal of Antimicrobial Chemotherapy·Kirsten J MeyerTheresa A Shapiro
Oct 10, 2019·Revista Da Sociedade Brasileira De Medicina Tropical·Taciana de Souza BayãoRodrigo Siqueira-Batista
Aug 15, 2018·Antimicrobial Agents and Chemotherapy·Nathaniel P NenortasTheresa A Shapiro
Feb 27, 2020·Clinical Pharmacokinetics·Valentin Al Jalali, Markus Zeitlinger
Jun 17, 2020·Chembiochem : a European Journal of Chemical Biology·Lena MünzkerWolfgang Jahnke
Mar 10, 2018·Current Medicinal Chemistry·Carolina Horta AndradePedro Vitor Lemos Cravo
Dec 19, 2018·Pharmaceutical Research·Helen W HernandezSean Ekins
Jan 13, 2019·Drugs·Emma D Deeks
Apr 28, 2018·Current Medicinal Chemistry·Stephen Patterson, Alan H Fairlamb
Aug 16, 2018·MedChemComm·Michael BerningerUlrike Holzgrabe
Apr 3, 2019·International Journal of Molecular Sciences·Cláudia Jassica Gonçalves MorenoMarcelo Sousa Silva
Dec 22, 2017·Emerging Topics in Life Sciences·Simon L CroftMichael P Barrett
Dec 25, 2017·Trends in Parasitology·Michael P Pollastri

Clinical Trials Mentioned


Related Concepts

Related Feeds

African Trypanosomiasis

African trypanosomiasis, also known as sleeping sickness, is an insect-borne parasitic disease of humans and other animals. It is caused by protozoa of the species Trypanosoma brucei and almost invariably progresses to death unless treated. Discover the latest research on African trypanosomiasis here.