Human African Trypanosomiasis (HAT), or sleeping sickness, is a life-threatening, neglected tropical disease (NTD). The etiological agent of HAT is the kinetoplastid protozoan parasite Trypanosoma brucei (T. b.). Two subspecies of this parasite are pathogenic for humans: T. b. gambiense (g-HAT) responsible for the chronic form of the disease occurring in western and central Africa, and T. b. rhodesiense (r-HAT) responsible for a more acute form occurring in eastern and southern Africa. Fexinidazole, a 5-nitroimidazole derivative DNA synthesis inhibitor, is the only, all-oral treatment for HAT and is indicated for use by adults and children (aged ≥ 6 years and weighing ≥ 20 kg) for both g-HAT stages[3]. This molecule and its metabolites (sulfoxide and sulfone) have shown trypanocidal activity in vitro in the 0.7-to-3.3 μM (0.2-to-0.9 μg/ml) range against all parasite strains tested. In vivo, fexinidazole is orally effective in curing both acute and chronic diseases in the mouse at doses of 100 mg/kg of body weight/day for 4 days and 200 mg/kg/day for 5 days, respectively[4].
Fexinidazole/非昔硝唑 细胞实验
Cell Line
Concentration
Treated Time
Description
References
L. donovani axenic amastigotes
L. donovani axenic amastigotes
Evaluate the in vitro activity of Fexinidazole against L. donovani axenic amastigotes, showing an EC50 of 2.8 ± 0.1 μM.
Sci Transl Med. 2012 Feb 1;4(119):119re1.
L. donovani promastigotes
L. donovani promastigotes
Evaluate the in vitro activity of Fexinidazole against L. donovani promastigotes, showing an EC50 of 5.6 ± 0.2 μM.
Sci Transl Med. 2012 Feb 1;4(119):119re1.
G. lamblia
G. lamblia
Evaluate the activity of Fexinidazole and its metabolites against Entamoeba histolytica HM1:IMSS strain, showing that Fexinidazole had an EC50 of 9.7 µM, while its metabolites (sulfoxide and sulfone) were more than 5-fold more active than the parent drug.
Antimicrob Agents Chemother. 2024 Jan 10;68(1):e0073123.
E. histolytica trophozoites
E. histolytica trophozoites
Evaluate the activity of Fexinidazole and its metabolites against Giardia lamblia WB strain, showing that Fexinidazole had an EC50 of 5.6 µM, while its metabolites (sulfoxide and sulfone) were more than 10-fold more active than the parent drug.
Antimicrob Agents Chemother. 2024 Jan 10;68(1):e0073123.
Trypanosoma brucei gambiense STIB930
Trypanosoma brucei gambiense STIB930
Evaluate in vitro trypanocidal activity against STIB930 strain, IC50 1.84 μM
Evaluate the efficacy of Fexinidazole in a mouse model of visceral leishmaniasis, showing that oral administration of 200 mg kg?1 once daily for 5 days suppressed infection by 98.4%.
Sci Transl Med. 2012 Feb 1;4(119):119re1.
C57BL/6 mice
Giardia lamblia infection model
Oral gavage
10 mg/kg
Once daily for 3 days
Evaluate the efficacy of Fexinidazole and its metabolites in a mouse model of Giardia lamblia infection, showing that Fexinidazole and its metabolites significantly reduced the infection.
Antimicrob Agents Chemother. 2024 Jan 10;68(1):e0073123.
Swiss mice
Mouse model infected with VL-10 or Colombiana strains of T. cruzi
Oral
300 mg/kg
Once daily for 20 days
To evaluate the therapeutic efficacy of Fexinidazole in T. cruzi-infected mice. The ELA assay demonstrated cure rates of ~71% and ~77% for VL-10 and Colombiana strains, respectively, showing superior efficacy compared to Benznidazole.
Front Immunol. 2024 Jan 12;14:1340755
NMRI mice
Acute T. b. rhodesiense infection model
Oral
100 mg/kg
Four consecutive days
Evaluate efficacy in acute infection model, 100 mg/kg/day orally for 4 days achieved 100% cure
Mouse models infected with different Trypanosoma cruzi strains
Oral
50, 100, 200, 300 mg/kg
7 or 20 consecutive days
To evaluate the efficacy of Fexinidazole against different Trypanosoma cruzi strains, results showed that Fexinidazole effectively suppressed parasitemia and prevented death in infected animals, with high cure rates in both acute and chronic phases.
Chagas Disease
... 展开 >> Trypanosomiasis, South American
South American Trypanosomiasis
Disease, Chagas 收起 <<
Phase 2
Unknown
February 2016
Bolivia
... 展开 >> Plataforma Atención Integral de Pacientes con Enfermedad de Chagas
Recruiting
Cochabamba, Bolivia
Contact: Faustino Torrico, MD 59177411905 foxtorrico@yahoo.com
Contact: Cristina Alonso, MD 59172211312 calonso@dndi.org
Principal Investigator: Faustino Torrico, MD
Plataforma de Atención Integral de Pacientes con Enfermedad de Chagas
Recruiting
Tarija, Bolivia
Contact: Lourdes O Daza, MD 5916672252 lourdesortizd@yahoo.es
Contact: Erika Ribeiro, Pharm D 59175969924 ecorreia@dndi.org
Principal Investigator: Lourdes O Daza, MD 收起 <<
Chagas Disease
... 展开 >> Trypanosomiasis, South American
South American Trypanosomiasis
Disease, Chagas 收起 <<
Phase 2
Unknown
February 2016
Bolivia
... 展开 >> Plataforma Atención Integral de Pacientes con Enfermedad de Chagas
Recruiting
Cochabamba, Bolivia
Contact: Faustino Torrico, MD 59177411905 foxtorrico@yahoo.com
Contact: Cristina Alonso, MD 59172211312 calonso@dndi.org
Principal Investigator: Faustino Torrico, MD
Plataforma de Atención Integral de Pacientes con Enfermedad de Chagas
Recruiting
Tarija, Bolivia
Contact: Lourdes O Daza, MD 5916672252 lourdesortizd@yahoo.es
Contact: Erika Ribeiro, Pharm D 59175969924 ecorreia@dndi.org
Principal Investigator: Lourdes O Daza, MD 收起 <<
Congo, The Democratic Republic... 展开 >> of the
Hôpital de Dipumba
Recruiting
Mbuji-Mayi, Kasaï Oriental, Congo, The Democratic Republic of the
Contact: Dieudonné Mpoyi, Doctor dmpoyi@dndi.org
Contact: Médard Ilunga, Doctor milunga@dndi.org
Principal Investigator: Dieudonné Mpoyi, Doctor
Sub-Investigator: Médard Ilunga, Doctor
Hopital General de réference
Recruiting
Bagata, Congo, The Democratic Republic of the
Contact: Papy Kavunga, MD plukula@dndi.org
Principal Investigator: Papy Kavunga, Doctor
Sub-Investigator: Mathieu Nkeri, Doctor
Sub-Investigator: John Twampo, Doctor
Hopital Général de réference
Recruiting
Bandundu, Congo, The Democratic Republic of the
Contact: Helen Mahenzi, MD hmahenzi@dndi.org
Principal Investigator: Helene Mahenzi, Doctor
Sub-Investigator: Joseph MAKAYA, Doctor
Sub-Investigator: Bedel Mulumba, Doctor
Hopital de Kimpese
Recruiting
Kimpese, Congo, The Democratic Republic of the
Contact: Jean-Papa Mavakala, Dr jpmavakala@dndi.org
Principal Investigator: Jean-Papa Mavakala, Dr
Hôpital Général de Référence Roi Baudouin
Recruiting
Kinshasa, Congo, The Democratic Republic of the
Contact: Luwawu Ntoya, Doctor lntoya@dndi.org
Principal Investigator: Luwawu Ntoya, Doctor
Sub-Investigator: Vincent Kobo, Doctor
Hopital Genral de Reference Masi MAnimba
Recruiting
Masi-Manimba, Congo, The Democratic Republic of the
Contact: Willy Kuziena, Doctor
Principal Investigator: Willy Kuziena Mindele, Doctor
Sub-Investigator: Augustin Kukembila Musoki, Doctor
Sub-Investigator: Felix Akwaso Masa, Doctor
Hopital General de réference
Recruiting
Mushie, Congo, The Democratic Republic of the
Contact: Guylain Mandula, MD gmandula@dndi.org
Principal Investigator: Guylain Mandula, Doctor
Sub-Investigator: Tim Mayala, Doctor
HGR Nkara
Recruiting
Nkara, Congo, The Democratic Republic of the
Contact: Steve Inzodi, Dr sinzodi@dndi.org
Principal Investigator: Steve Inzodi, Dr
Guinea
Hopital de Dubreka
Recruiting
Dubreka, Guinea
Contact: Mariame Camara, Dr mcamara@dndi.org
Principal Investigator: Mariame Camara, Dr 收起 <<
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