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| Name | Class |
|---|---|
| PhinC Development | INDUSTRY |
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The purpose of this study is to determine whether benznidazole and E1224 should be administered concomitantly in patients with Chagas Disease as not enough data are available. This study aims to assess cross interactions of these two compounds.
Benznidazole and E1224 are intended to be administered concomitantly in patients with Chagas disease. Thus, an in vivo interaction study in healthy volunteers may be justified as the two drugs are intended to be administered concomitantly in patients and no in vivo nor in vitro data are available.
In addition both interactions (potential for benznidazole to interact on the pharmacokinetic (PK) of E1224 and potential for E1224 on the PK of benznidazole should be studied.
Benznidazole t1/2 is quite short (12 h) whereas E1224 t1/2 is very long (more than 200 h). Therefore it was chosen to study the interaction of E1224 at steady-state while interaction of benznidazole after single dose appears more appropriate instead of a classical randomized cross-over design.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Benznidazole and E1224 | Other | Benznidazole and E1224 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Benznidazole | Drug | Benznidazole single dose (2.5 mg/kg) at Day 1. Benznidazole single dose (2.5 mg/kg) at Day 9*. Benznidazole multiple dose (2.5 mg/kg twice daily) from Day 12* until Day 15. |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum serum concentration (Cmax) of Benznidazole | BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly. | Day 1 and day 9 |
| Time of occurrence of maximum plasma concentration (tmax) of Benznidazole | BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly. | Day 1 and day 9 |
| Area under the serum concentration versus time curve from time zero to the time (t) corresponding to the last quantifiable concentration (AUC 0-t) of Benznidazole | BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly. | Day 1 and day 9 |
| Area under the concentration-time curve from time zero to infinity with extrapolation of the terminal phase (AUC 0-∞) of Benznidazole | BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly. | Day 1 and day 9 |
| Terminal half-life (t1/2) of Benznidazole | BNZ PK parameter following single dose to investigate the possible drug-drug interaction between BNZ and E1224 through evaluation of the PK characteristics of both drugs when given alone or concomitantly. | Day 1 and day 9 |
| Maximum serum concentration (Cmax) of Ravuconazole. |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of Adverse Events (AEs) | Monitoring for the occurrence of adverse events (AEs) | Through study completion, i.e up to 22 days. |
| Clinically significant alterations in pulse rate | Parameter to assess the safety and tolerability of multiple oral doses of BNZ and E1224 given in healthy male subjects. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Isabela Ribeiro, MD | Drugs for Neglected Diseases initiative | Study Chair |
| Ethel Feleder, MD | F.P. Clinical Pharma Clinical Research Unit | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| FP Clinical Pharma - Juncal 4484 - 3o piso | Buenos Aires | C1425BAB | Argentina |
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| ID | Term |
|---|---|
| D014355 | Chagas Disease |
| ID | Term |
|---|---|
| D014352 | Trypanosomiasis |
| D056986 | Euglenozoa Infections |
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
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| ID | Term |
|---|---|
| C009999 | benzonidazole |
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| E1224 | Drug | E1224 multiple dose 400 mg loading dose once daily for 3 days (i.e. from Day 4 to Day 6 followed by maintenance dose 100mg once daily for 9 days (from Day 7 to Day15). On Day 9 and from Day 12 to Day 15, E1224 and benznidazole will be given concomitantly. |
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PK parameter of ravuconazole following multiple dose to investigate the possible drug-drug interaction between BNZ and E1224 (prodrug of ravuconazole) through evaluation of the PK characteristics of both drugs when given alone or concomitantly. |
| Day 8 and day 15, day 6 (morning pre-dose), day 7 (morning pre-dose), day 8 (morning pre-dose), day 13 (morning pre-dose), day 14 (morning pre-dose), and day 15 (morning pre-dose) |
| Time of occurrence of maximum plasma concentration (tmax) of Ravuconazole. | PK parameter of ravuconazole following multiple dose to investigate the possible drug-drug interaction between BNZ and E1224 (prodrug of ravuconazole) through evaluation of the PK characteristics of both drugs when given alone or concomitantly. | Day 8 and day 15, day 6 (morning pre-dose), day 7 (morning pre-dose), day 8 (morning pre-dose), day 13 (morning pre-dose), day 14 (morning pre-dose), and day 15 (morning pre-dose) |
| The area under the blood drug concentration vs. time curve from time zero (pre-dose) to 24 h post-dose (AUC 0-24) | PK parameter of ravuconazole following multiple dose to investigate the possible drug-drug interaction between BNZ and E1224 (prodrug of ravuconazole) through evaluation of the PK characteristics of both drugs when given alone or concomitantly. | Day 8 and day 15, day 6 (morning pre-dose), day 7 (morning pre-dose), day 8 (morning pre-dose), day 13 (morning pre-dose), day 14 (morning pre-dose), and day 15 (morning pre-dose) |
| Through study completion, i.e up to 22 days. |
| Clinically significant alterations in blood pressure | Parameter to assess the safety and tolerability of multiple oral doses of BNZ and E1224 given in healthy male subjects. | Through study completion, i.e up to 22 days. |
| Clinically significant alterations in 12-lead ECG | Parameter to assess the safety and tolerability of multiple oral doses of BNZ and E1224 given in healthy male subjects | Through study completion, i.e up to 22 days. |
| Clinically significant Haematology abnormalities (hemoglobin, RBC, hematocrit, MCV, MCH, MCHC, WBC, including differential, platelet counts) | Parameter to assess the safety and tolerability of multiple oral doses of BNZ and E1224 given in healthy male subjects. | Day 1, Day 4, Day 7, Day 9, Day 10, Day 12, Day 13, Day 14 and Day 15 pre morning dose |
| Clinically significant Biochemistry abnormalities (albumin (ALB), ALP, ALT, AST, gamma-glutamyl transferase (GGT), chlorides (Cl-), creatinine, glucose (GLU), potassium (K+), sodium (Na+), total bilirubin (TBIL), total proteins (TP), Urea. | Parameter to assess the safety and tolerability of multiple oral doses of BNZ and E1224 given in healthy male subjects. | Day 1, Day 4, Day 7, Day 9, Day 10, Day 12, Day 13, Day 14 and Day 15 pre morning dose |
| Clinically significant Urinalysis abnormalities (leukocytes, pH, proteins, urobilinogen, blood, nitrites, glucose, ketone bodies, bilirubin). | Parameter to assess the safety and tolerability of multiple oral doses of BNZ and E1224 given in healthy male subjects. | Screening and day 22 |
| D007239 |
| Infections |
| D000079426 | Vector Borne Diseases |