Determination of the Optimal Single Dose Treatment for Acoziborole, a Novel Drug for the Treatment of Human African Trypanosomiasis : First-in-Human Study
© 2023. The Author(s)..
BACKGROUND AND OBJECTIVES: Acoziborole is a novel boron-containing candidate developed as an oral drug for the treatment of human African trypanosomiasis (HAT). Results from preclinical studies allowed progression to Phase 1 trials. We aimed to determine the best dose regimen for all stages of HAT.
METHODS: Acoziborole was assessed in 128 healthy adult males of sub-Saharan African origin living in France. The study included a single oral administration of a 20- to 1200-mg dose in a randomised double-blind study in cohorts of 8 (6 active, 2 placebo) to assess safety, tolerability, and pharmacokinetics. In three additional open cohorts of 6 participants, the effect of activated charcoal was evaluated, bioequivalence of capsules versus tablets was assessed, and safety in the 960-mg tablet cohorts was monitored.
RESULTS: Acoziborole was well tolerated at all doses tested; no dose-related adverse events were observed. The drug appeared rapidly in plasma (at 1 h), reached tmax between 24 and 72 h, and remained stable for up to 96 h, after which a slow decrease was quantifiable until 14 weeks after dosing. Charcoal had little impact on the enterohepatic recirculation effect, except for the 20-mg dose. Bioequivalence between capsule and tablet formulations was demonstrated. The therapeutic single dose for administration under fasted conditions was fixed to 960 mg. The maximum administered dose was 1200 mg.
CONCLUSIONS: This study showed that acoziborole could be safely assessed in patients as a potential single-dose oral cure for both stages of gambiense HAT.
TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov: NCT01533961.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:62 |
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| Enthalten in: |
Clinical pharmacokinetics - 62(2023), 3 vom: 10. März, Seite 481-491 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tarral, Antoine [VerfasserIn] |
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| Links: |
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| Themen: |
Antiprotozoal Agents |
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| Anmerkungen: |
Date Completed 29.03.2023 Date Revised 06.04.2023 published: Print-Electronic ClinicalTrials.gov: NCT01533961 Citation Status MEDLINE |
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| doi: |
10.1007/s40262-023-01216-8 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM352730935 |
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| 500 | |a Date Revised 06.04.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT01533961 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a BACKGROUND AND OBJECTIVES: Acoziborole is a novel boron-containing candidate developed as an oral drug for the treatment of human African trypanosomiasis (HAT). Results from preclinical studies allowed progression to Phase 1 trials. We aimed to determine the best dose regimen for all stages of HAT | ||
| 520 | |a METHODS: Acoziborole was assessed in 128 healthy adult males of sub-Saharan African origin living in France. The study included a single oral administration of a 20- to 1200-mg dose in a randomised double-blind study in cohorts of 8 (6 active, 2 placebo) to assess safety, tolerability, and pharmacokinetics. In three additional open cohorts of 6 participants, the effect of activated charcoal was evaluated, bioequivalence of capsules versus tablets was assessed, and safety in the 960-mg tablet cohorts was monitored | ||
| 520 | |a RESULTS: Acoziborole was well tolerated at all doses tested; no dose-related adverse events were observed. The drug appeared rapidly in plasma (at 1 h), reached tmax between 24 and 72 h, and remained stable for up to 96 h, after which a slow decrease was quantifiable until 14 weeks after dosing. Charcoal had little impact on the enterohepatic recirculation effect, except for the 20-mg dose. Bioequivalence between capsule and tablet formulations was demonstrated. The therapeutic single dose for administration under fasted conditions was fixed to 960 mg. The maximum administered dose was 1200 mg | ||
| 520 | |a CONCLUSIONS: This study showed that acoziborole could be safely assessed in patients as a potential single-dose oral cure for both stages of gambiense HAT | ||
| 520 | |a TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov: NCT01533961 | ||
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| 700 | 1 | |a Donazzolo, Yves |e verfasserin |4 aut | |
| 700 | 1 | |a Latreille, Mathilde |e verfasserin |4 aut | |
| 700 | 1 | |a Felices, Mathieu |e verfasserin |4 aut | |
| 700 | 1 | |a Gualano, Virginie |e verfasserin |4 aut | |
| 700 | 1 | |a Delhomme, Sophie |e verfasserin |4 aut | |
| 700 | 1 | |a Valverde Mordt, Olaf |e verfasserin |4 aut | |
| 700 | 1 | |a Blesson, Severine |e verfasserin |4 aut | |
| 700 | 1 | |a Voiriot, Pascal |e verfasserin |4 aut | |
| 700 | 1 | |a Strub-Wourgaft, Nathalie |e verfasserin |4 aut | |
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