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Study to assess the relative Bioavailability To assess the relative bioavailability of three formulations of nifurtimox 30 mg tablets exhibiting different in vitro dissolution profiles To assess the pharmacokinetics (PK) of nifurtimox To investigate the safety and tolerability of nifurtimox.
Primary objective is to assess the relative bioavailability of three formulations of nifurtimox 30 mg tablets exhibiting different in vitro dissolution profiles (slow, medium, and fast, whereby "medium" represents the drug product currently used in clinical Phase 3 studies) under fed conditions in adult male and female patients with Chagas' disease.
A secondary objective of the study is to assess the relative bioavailability of nifurtimox after a single oral dose of 30 mg and 120 mg To assess the pharmacokinetics (PK) of nifurtimox To investigate the safety and tolerability of nifurtimox..
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GRP1 - Assess relative bioavailability(3-way cross-over) | Experimental | GROUP 1 (Treatments A, B, C) All 3 treatments in Group 1 consist of a dose of 120 mg nifurtimox (4 x 30 mg tablets). Participants received the 3 treatments in one of six treatment sequences under fed condition. Treatment A, dose administration with fast in vitro dissolution characteristics Treatment B, dose administration with medium in vitro dissolution characteristics Treatment C, dose administration with slow in vitro dissolution characteristics |
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| GRP2 - Assess relative bioavailability (2-way cross-over) | Experimental | GROUP 2 (Treatments D and E) Participants received the 2 treatments in one of two treatment sequences under fed condition. Treatment D, a single dose 30 mg nifurtimox dose with medium in vitro dissolution characteristics Treatment E, a single dose of 120 mg nifurtimox |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Nifurtimox (Lampit, BAYA2502) | Drug | Oral Intake of 4 x 30 mg nifurtimox tablets for treatment A-C; Oral Intake of 1 x 30 mg nifurtimox tablets for treatment D Oral intake of 1 x 120 mg nifurtimox tablet for treatment E |
| Measure | Description | Time Frame |
|---|---|---|
| AUC(0-tlast) of nifurtimox | AUC(0-tlast):Area under the drug-concentration vs. time curve of nifurtimox from time 0 to the last data point | 0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,15 hour |
| Cmax of nifurtimox | Cmax: Maximum observed drug concentration in measured matrix after single dose administration | 0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,15 hour |
| AUC of nifurtimox | AUC: Area under the concentration versus time curve from zero to infinity after single (first) dose | 0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,15 hour |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants with adverse events | up to 8 weeks | |
| AUC divided by dose: AUC/D | 0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,15 hour | |
| AUC(0-tlast) divided by dose: AUC(0-tlast)/D |
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Inclusion Criteria
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| Bayer Study Director | Bayer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| FP Clinical Pharma | Buenos Aires | Ciudad Auton. de Buenos Aires | C1425BAB | Argentina |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34265407 | Derived | Stass H, Just S, Weimann B, Ince I, Willmann S, Feleder E, Freitas C, Yerino G, Munster U. Clinical investigation of the biopharmaceutical characteristics of nifurtimox tablets - Implications for quality control and application. Eur J Pharm Sci. 2021 Nov 1;166:105940. doi: 10.1016/j.ejps.2021.105940. Epub 2021 Jul 12. |
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Group 1 ( Treatment A,B,C - 3 way cross-over), Group 2 ( Treatment D, E - 2 way cross over)
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| 0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,15 hour |
| Cmax divided by dose: Cmax/D | 0, 15, 30, 45 min, 1, 1.5, 2, 2.5, 3, 4, 6, 8,12,15 hour |
| ID | Term |
|---|---|
| D014355 | Chagas Disease |
| ID | Term |
|---|---|
| D014352 | Trypanosomiasis |
| D056986 | Euglenozoa Infections |
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000079426 | Vector Borne Diseases |
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| ID | Term |
|---|---|
| D009547 | Nifurtimox |
| ID | Term |
|---|---|
| D009581 | Nitrofurans |
| D009574 | Nitro Compounds |
| D009930 | Organic Chemicals |
| D013843 | Thiazines |
| D013457 | Sulfur Compounds |
| D005663 | Furans |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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