Clinical Trial: Prospective Study of a Pediatric Nifurtimox Formulation for Chagas' Disease
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: Prospective, Historically Controlled Study to Evaluate the Efficacy and Safety of a New Pediatric Formulation of Nifurtimox in Children Aged 0 to 17 Years With Chagas' Disease
Brief Summary: This study was designed to develop a better understanding of the efficacy, safety/tolerability, and pharmacokinetics (PK) (absorption, distribution, metabolism, and elimination) of nifurtimox in children with a diagnosis of Chagas' disease (Trypanosoma cruzi infection) using pediatric formulations.
Detailed Summary:
Sponsor: Bayer
Current Primary Outcome:
- Superiority of nifurtimox to historical untreated control in children: Sero-conversion for subjects ≤ 8 months of age at randomization [ Time Frame: 360 days from end of treatment [EOT] ]Sero-conversion: defined as negative antibody concentration to Trypanosoma cruzi Binary variables: CURE (negative ELISA result) / NO CURE (positive ELISA result)
- Superiorty of nifurtimox to historical untreated control in children: Sero-reduction for subjects ≥ 8 months to <18 years of age [ Time Frame: 360 days from end of treatment [EOT] ]Sero-reduction:defined as Recombinant ELISA (enzyme-linked immune sorbent assay) serology tests based upon a target of ≥ 20% decrease in antibody concentration to Trypanosoma cruzi Binary variables: CURE (20% or more reduction in antibody) / NO CURE ( less than 20% reduction in antibody)
Original Primary Outcome:
- Superiority of nifurtimox to historical untreated control in children: Sero-conversion for subjects ≤ 8 months of age at randomization [ Time Frame: 360 days from end of treatment [EOT] ]Sero-conversion: defined as negative antibody concentration to Trypanosoma cruzi
- Superiority of nifurtimox to historical untreated control in children: Sero-reduction for subjects ≥ 8 months to <18 years of age [ Time Frame: 360 days from end of treatment [EOT] ]Sero-reduction:defined as Recombinant ELISA (enzyme-linked immune sorbent assay) serology tests based upon a target of ≥ 20% decrease in antibody concentration to Trypanosoma cruzi
Current Secondary Outcome:
- Comparability of a 60-day regimen of nifurtimox to historical active control (benznidazole) as sero-reduction or sero-conversion [ Time Frame: up to 420 days (Visit 11) post-treatment ]Binary variables : CURE (negative ELISA result or ≥ 20% reduction in antibody concentration) / NO CURE (positive ELISA result or less than 20% reduction in antibody).
- Comparability of a 30-day regimen of nifurtimox to a 60-day regimen of nifurtimox as sero-reduction or sero-conversion and to qualitative polymerase chain reaction (qPCR) [ Time Frame: up to 420 days (Visit 11) post-treatment ]Binary variables :CURE (negative ELISA result , ≥20% reduction in antibody concentration, or non-reactive PCR test) / NO CURE (positive ELISA result , less than 20% reduction in antibody, or , reactive PCR test).
- Relationship of conventional serology (as sero-reduction or sero-conversion) to qPCR using frequencies of matches and mismatches to assess agreement [ Time Frame: up to 420 days (Visit 11) post-treatment ]Comparison of CURE / NO CURE results for ELISA tests and PCR tests.
- Relationship of non-conventional serology to conventional serology [ Time Frame: up to 420 days (Visit 11) post-treatment ]Compare CURE / NO CURE results for non-conventional ELISA and conventional ELISA tests.
- Safety/tolerability profile of nifurtimox by assessing the number of participants with Adverse Event as a measure of safety and tolerability [ Time Frame: up to 420 days (Visit 11) post-treatment ]
- Safety/tolerability profile of nifurtimox by laboratory parameters [ Time Frame: up to 420 days (Visit 11) post-treatment ]Hematology Blood chemistry Urinalysis
- Safety/tolerability profile of nifurtimox by electrocardiogram (ECG) monitoring [ Time Frame: up to 420 days (Visit 11) post-treatment ]
- Safety/tolerability profile of nifurtimox by laboratory parameters vital sign measurements [ Time Frame: up to 420 days (Visit 11) post-treatment ]Blood pressure Heart rate Respiratory rate Temperature
- Safety/tolerability profile of nifurtimox by physical examinations [ Time Frame: up to 420 days (Visit 11) post-treatment ]Neurological examinations
- Pharmacokinetics - Plasma concentration time courses in children: maximum concentration (Cmax) of nifurtimox, after first dose and at steady state [ Time Frame: up to 60 days (Visit 8) ]
- Pharmacokinetics - Plasma concentration time courses in children: time to maximum plasma concentration (Tmax) of nifurtimox, after first dose and at steady state [ Time Frame: up to 60 days (Visit 8) ]
- Pharmacokinetics - Plasma concentration time courses in children: Area under the curve (AUC), regarding plasma nifurtimox concentration-time curve after first dose and at steady state [ Time Frame: up to 60 days (Visit 8) ]
- Pharmacokinetics - Plasma concentration time courses in children: Half-life (t1/2) of nifurtimox, after first dose and at steady state [ Time Frame: up to 60 days (Visit 8) ]
Original Secondary Outcome:
- Comparability of a 60-day regimen of nifurtimox to historical active control (benznidazole) as sero-reduction or sero-conversion [ Time Frame: up to 420 days (Visit 11) post-treatment ]
- Comparability of a 30-day regimen of nifurtimox to a 60-day regimen of nifurtimox as sero-reduction or sero-conversion and to qualitative polymerase chain reaction (qPCR) [ Time Frame: up to 420 days (Visit 11) post-treatment ]
- Relationship of conventional serology (as sero-reduction or sero-conversion) to qPCR using frequencies of matches and mismatches to assess agreement [ Time Frame: up to 420 days (Visit 11) post-treatment ]
- Relationship of non-conventional serology to conventional serology [ Time Frame: up to 420 days (Visit 11) post-treatment ]
- Safety/tolerability profile of nifurtimox by assessing the number of participants with Adverse Event as a measure of safety and tolerability [ Time Frame: up to 420 days (Visit 11) post-treatment ]
- Safety/tolerability profile of nifurtimox by laboratory parameters [ Time Frame: up to 420 days (Visit 11) post-treatment ]Hematology Blood chemistry Urinalysis
- Safety/tolerability profile of nifurtimox by electrocardiogram (ECG) monitoring [ Time Frame: up to 420 days (Visit 11) post-treatment ]
- Safety/tolerability profile of nifurtimox by laboratory parameters vital sign measurements [ Time Frame: up to 420 days (Visit 11) post-treatment ]Blood pressure Heart rate Respiratory rate Temperature
- Safety/tolerability profile of nifurtimox by physical examinations [ Time Frame: up to 420 days (Visit 11) post-treatment ]Neurological examinations
- Pharmacokinetics - Plasma concentration time courses in children: maximum concentration (Cmax) of nifurtimox, after first dose and at steady state [ Time Frame: up to 60 days (Visit 8) ]
- Pharmacokinetics - Plasma concentration time courses in children: time to maximum plasma concentration (Tmax) of nifurtimox, after first dose and at steady state [ Time Frame: up to 60 days (Visit 8) ]
- Pharmacokinetics - Plasma concentration time courses in children: Area under the curve (AUC), regarding plasma nifurtimox concentration-time curve after first dose and at steady state [ Time Frame: up to 60 days (Visit 8) ]
- Pharmacokinetics - Plasma concentration time courses in children: Half-life (t1/2) of nifurtimox, after first dose and at steady state [ Time Frame: up to 60 days (Visit 8) ]
Information By: Bayer
Dates:
Date Received: December 7, 2015
Date Started: January 27, 2016
Date Completion: November 30, 2018
Last Updated: May 9, 2017
Last Verified: May 2017