Population Pharmacokinetics Study of Benznidazole in Children With Chagas'Disease

NCT01549236 | Completed Phase 4

• 1 other identifier: DNDi-CD-PEDBZ-001
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to describe the population pharmacokinetics parameters of benznidazole in children with acute or early chronic indeterminate form of Chagas Disease.

Conditions

Chagas' Disease

Keywords

Chagas Disease; Trypanosoma Cruzi; T.Cruzi

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetics Endpoints

  Plasma level concentrations of benznidazol determined in children at first day of treatment (Day 0), steady state phase (D7 and Day 30) and at the end of treatment (Day 60). Population pharmacokinetics parameters of benznidazole in children, including CL, Vd, and Ka. Individual AUC. Individual Cmax. Individual Cmin. Individual t1/2 will be estimated using population parameters.

  Day 60

Secondary Outcomes (3)

• Efficacy Endpoints

  Day 60

• Safety endpoints

  Day 60

• Safety Endpoints

  Day 60

Interventions

Benznidazole 12,5mg or 100mg DRUG

All 80 subjects recruited into the study will receive treatment with: \- Benznidazole (Laboratório Farmacêutico do Estado de Pernambuco -LAFEPE - Recife - Brazil; tablet 12.5mg or 100mg), 7.5 mg/Kg/day PO (actual range of 5.5-8.5 mg/Kg/d), divided in two daily doses, for 60 days.

Also known as: BNZ

Eligibility Criteria

• Age: 1 Day - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age between newborn (1day) - 12 years
• Diagnosis of T. cruzi infection by:
• Direct microscopic examination or
• Conventional serology, at least two positive tests (ELISA, IIF or HAI)
• Written informed consent form by parent/ legal representative
• Children assent if \> 7 years

You may not qualify if:

• Pre-term (\< 37 weeks gestational age) or weight \< 2500 g
• Female subject who has reached menarche
• Subjects presenting any other acute or chronic health conditions, that in the opinion of the PI, may interfere with the PK, efficacy and/or safety evaluation of the study drug
• Known history of hypersensitivity or serious adverse reactions to nitro- imidazoles
• History of CD treatment with benznidazole or nifurtimox in the past
• Immunocompromised patients (clinical history compatible with HIV infection, primary immunodeficiency or prolonged treatment with corticosteroids or other immunosuppressive drugs)
• Abnormal laboratory test values at screening for the following parameters: total WBC count, platelet count, ALT, AST, total bilirubin and creatinine.
• Inability to comply with follow-up and/or not having a permanent address
• Any condition that prevents the subject from taking oral medication

Sponsors & Collaborators

• Drugs for Neglected Diseases: lead
• LAT Research: collaborator

Study Sites (3)

Hospital General de Niños Ricardo Gutierrez

Buenos Aires, C1425, Argentina

Location

Hospital Público Materno Infantil

Salta, CP3400, Argentina

Location

Hospital de Niños "Doctor Héctor Quintana"

San Salvador de Jujuy, CP4600, Argentina

Location

Related Publications (6)

• Andrade AL, Martelli CM, Oliveira RM, Silva SA, Aires AI, Soussumi LM, Covas DT, Silva LS, Andrade JG, Travassos LR, Almeida IC. Short report: benznidazole efficacy among Trypanosoma cruzi-infected adolescents after a six-year follow-up. Am J Trop Med Hyg. 2004 Nov;71(5):594-7.

  PMID: 15569790 BACKGROUND

• de Andrade AL, Zicker F, de Oliveira RM, Almeida Silva S, Luquetti A, Travassos LR, Almeida IC, de Andrade SS, de Andrade JG, Martelli CM. Randomised trial of efficacy of benznidazole in treatment of early Trypanosoma cruzi infection. Lancet. 1996 Nov 23;348(9039):1407-13. doi: 10.1016/s0140-6736(96)04128-1.

  PMID: 8937280 BACKGROUND

• Sosa-Estani S, Segura EL. Etiological treatment in patients infected by Trypanosoma cruzi: experiences in Argentina. Curr Opin Infect Dis. 2006 Dec;19(6):583-7. doi: 10.1097/01.qco.0000247592.21295.a5.

  PMID: 17075335 BACKGROUND

• Ribeiro I, Sevcsik AM, Alves F, Diap G, Don R, Harhay MO, Chang S, Pecoul B. New, improved treatments for Chagas disease: from the R&D pipeline to the patients. PLoS Negl Trop Dis. 2009 Jul 7;3(7):e484. doi: 10.1371/journal.pntd.0000484. No abstract available.

  PMID: 19582163 BACKGROUND

• Garcia-Bournissen F, Altcheh J, Giglio N, Mastrantonio G, Della Vedova CO, Koren G. Pediatric clinical pharmacology studies in Chagas disease: focus on Argentina. Paediatr Drugs. 2009;11(1):33-7. doi: 10.2165/0148581-200911010-00012.

  PMID: 19127950 BACKGROUND

• Altcheh J, Moscatelli G, Caruso M, Moroni S, Bisio M, Miranda MR, Monla C, Vaina M, Valdez M, Moran L, Ramirez T, Patino OL, Riarte A, Gonzalez N, Fernandes J, Alves F, Ribeiro I, Garcia-Bournissen F. Population pharmacokinetics of benznidazole in neonates, infants and children using a new pediatric formulation. PLoS Negl Trop Dis. 2023 May 31;17(5):e0010850. doi: 10.1371/journal.pntd.0010850. eCollection 2023 May.

  PMID: 37256863 DERIVED

Related Links

• Drugs for Neglected Diseases initiative

MeSH Terms

Conditions

Chagas Disease

Condition Hierarchy (Ancestors)

Trypanosomiasis; Euglenozoa Infections; Protozoan Infections; Parasitic Diseases; Infections; Vector Borne Diseases

Study Officials

• Jaime Altcheh, MD

  Argentina: FIPEC Foundation (Fundación para el Estudio de las Infecciones Parasitarias y Enfermedad de Chagas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2012
• First Posted: March 9, 2012
• Study Start: May 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: October 1, 2012
• Last Updated: June 25, 2018

Record last verified: 2012-08

Locations

AR (3)