Chronic Chagas Disease, Indeterminate Clinical Trial
Official title:
Phase 2 Randomized, Multicenter, Placebo-controlled, Safety and Efficacy Study to Evaluate Three Oral E1224 Dosing Regimens and Benznidazole for the Treatment of Adult Patients With Chronic Indeterminate Chagas Disease
This study will assess the safety and efficacy of E1224, a pro-drug of ravuconazole, in individuals with chronic indeterminate Chagas disease recruited in research centres in Tarija and Cochabamba, Bolivia.
| Status | Recruiting |
| Enrollment | 230 |
| Est. completion date | December 2013 |
| Est. primary completion date | August 2012 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years to 50 Years |
| Eligibility |
Screening Criteria: - Age >18 to < 50 years - Weight > 40 kg - Diagnosis of T. cruzi infection by conventional serology (a minimum of two out of three positive tests [enzyme linked immunosorbent assay (ELISA), indirect immunofluorescence (IIF), or hemagglutination inhibition (HAI)]) - Signed, written informed consent form - No signs and/or symptoms of the chronic cardiac and/or digestive form of CD - No acute or chronic health conditions that may interfere with the efficacy and/or safety evaluation of the study drug - No formal contraindication to BZN and E1224 - No known history of hypersensitivity, allergic, or serious adverse reactions to the study drugs - No history of CD treatment with BZN or NFX at any time in the past - No history of systemic treatment with itraconazole, ketoconazole, posaconazole, isavuconazole, or allopurinol in the past Inclusion Criteria: - Confirmed diagnosis of T. cruzi infection by serial qualitative PCR AND Conventional serology - Women in reproductive age must have a negative serum pregnancy test at screening, must not be breastfeeding, and consistently use and/or have partner consistently use an adequate contraceptive method - Normal ECG at screening Exclusion Criteria: - Abnormal laboratory test values at screening for the following parameters: total White Blood Cells (WBC) count, platelet count, alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin, or creatinine; or gamma-glutamyl transferase (GGT) - History of alcohol abuse or any other drug addiction (as specified in the Study Manual of Operations) - Any condition that prevents the patient from taking oral medication - Any concomitant use of antimicrobial or antiparasitic agents |
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Bolivia | Plataforma de Atención Integral a los Pacientes con Enfermidad de Chagas | Cochabamba | |
| Bolivia | Plataforma de Atención Integral a los Pacientes con Enfermidad de Chagas | Tarija |
| Lead Sponsor | Collaborator |
|---|---|
| Drugs for Neglected Diseases | Eisai Co., Ltd. |
Bolivia,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Serial negative qualitative Polymerase Chain Reaction (PCR) results (3 negative PCR results from 3 samples to be collected over 7 days) as a measure of parasitological cure at end of treatment | To determine whether at least one of three dosing regimens of orally administered E1224 is more efficacious than placebo in individuals with chronic indeterminate CD, by determining the number of patients who convert from positive to negative in serial, qualitative PCR test results | Day 65 (end of treatment) | No |
| Secondary | Consistently negative serial qualitative PCR as a measure of sustained parasitological eradication | 4, 6 and 12 months follow-up | No | |
| Secondary | Qualitative PCR as a measure of parasite eradication | Day 8, 15, 36 , 65 and at 4, 6 and 12 months follow-up | No | |
| Secondary | Quantitative PCR as a measure of change in parasite load over time | Day 8, 15, 36, 65 and at 4, 6 and 12 months follow-up | No | |
| Secondary | Incidence of serological conversion to negative and changes in titers over time as measured by conventional and non-conventional serologies | Day 65 and at 4, 6 and 12 months after treatment | No | |
| Secondary | Changes in the levels of biomarkers over time: brain natriuretic peptide, troponin T, selected prothrombotic factors, lytic antibodies, apolipoprotein A1 and multiplex serodiagnostic assay | Day 36 , 65 and at 4, 6 and 12 months follow-up | No | |
| Secondary | Area under the plasma concentration versus time curve (AUC), Peak Plasma Concentration (Cmax), Minimum Plasma Concentration (Cmin), Clearance, Volume of Distribution , and Plasma Terminal Half-Life (t1/2) of ravuconazole and benznidazole | Samples for population pharmacokinetics parameters of ravuconazole and benznidazole will be collected at randomly selected time points on Days 1, 2 and 3. | Day 0 (pre-dose), Day 1 (after 1st dose), Day 2, Day 3, steady-state phase (D8-D50), at the end of treatment (D65) and at the 4 months follow-up visit | No |
| Secondary | Incidence and severity of adverse events (clinical and laboratory) | Up to 12 months follow-up | Yes | |
| Secondary | Incidence of Serious Adverse Events and/or adverse events leading to treatment discontinuation | Up to 12 months follow-up | Yes | |
| Secondary | Early and late predictors of sustainable response to treatments | Up to 12 months follow-up | No | |
| Secondary | Correlation of pharmacokinetic parameters with parasitological response, changes in biomarkers and safety outcomes | Day 8, 15, 36, 65, and at 4, 6 months and 12 months follow-up | Yes |