Cadazolid Gets Mixed Phase III Results as C. Difficile Treatment

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The drug met endpoints of one phase III trial, but not another.

Phase III studies are showing mixed results for Actelion Pharmaceuticals’ novel anti-infective drug cadazolid versus antibiotic vancomycin for the treatment of clostridium difficile-associated diarrhea (CDAD).

According to a company statement, the organization’s phase III IMPACT 1 study met its primary endpoint, while the second phase III study, IMPACT 2, did not.

The primary endpoint in both studies was the clinical cure rate at the end of treatment. This was defined as the resolution of diarrhea (less than or equal to 3 unformed bowel movements per day for at least 2 consecutive days), and no further need for CDAD therapy maintained for 2 days after the end of treatment with cadazolid.

The two studies monitored a total of 1263 patients worldwide and compared the efficacy and safety of a 250 mg dose of cadazolid administered twice daily for 10 days versus 125 mg of vancomycin — the current standard of care for patients with CDAD – administered four times daily for 10 days.

According to Actelion, cadazolid demonstrated acceptable tolerability and safety profile in the phase III impact program, consistent with the results of previous trials.

In phase I and II trials, cadazolid was shown to be safe, well tolerated and efficacious, positioning itself as a potential future viable therapeutic option for CDA, according to Actelion. Similarly, in preclinical studies, cadazolid showed potent in vitro activity against Clostridium difficile isolates, and a low propensity for resistance development. Moreover, cadazolid had very limited impact on normal gut microflora in a human gut model of CDAD.

“The results of the Phase II study indicate that the effect of all doses of cadazolid were numerically similar to, or better than vancomycin on key endpoints including CDAD clinical cure rates as well as sustained cure rates,” according to a company statement.

However, mixed results from the phase III trial have raised questions about the drug’s efficacy.

Actelion Pharmaceuticals “will now work diligently to complete the analyses of the full study results and detailed results will be made available through scientific disclosure at upcoming congresses and in peer-reviewed publications,” the statement read.

Cadazolid is a novel quinoxolidinone antibiotic and a strong inhibitor of Clostridium difficile protein synthesis, leading to suppression of toxin production and spore formation.

It was previously investigated in a randomized, double-blind, active reference group phase II study, with 84 patients randomized 1:1:1:1 to 250, 500 or 1000 mg doses of cadazolid or 125 mg or oral vancomycin.

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