New benznidazole regimens:
The E1224 proof-of-concept trial carried out in 2013 showed a good safety profile and was effective at clearing the parasite, but efficacy was not sustained. Benznidazole, the standard treatment for Chagas, showed sustained efficacy until 12 months post-therapy, but was associated with side effects that resulted in treatment discontinuation. An expert meeting in 2014 reviewed the available data in support of the evaluation of benznidazole-sparing (shorter duration courses and lower dosing) regimens for Chagas disease. Proof-of-concept evaluation of new treatment regimens of benznidazole in monotherapy or in combination with E1224, for the treatment of adult patients with chronic Chagas disease, will be initiated in 2015, to determine if the safety and tolerability issues of benznidazole can be managed by reduced doses and treatment duration.
Within the context of the partnership between DNDi and Eisai Co. Ltd for the development of E1224, a Phase I drug-drug interaction study was performed in 2014, to assess the safety and pharmacokinetics interaction of E1224 and benznidazole administered first separately and then in combination in healthy human volunteers. The study was undertaken in a Phase I clinical unit in Buenos Aires, Argentina. Twenty-eight healthy human volunteers were recruited and the trial concluded with no major clinically relevant safety or tolerability issues identified.