Date: 2012-12-21
Type of information: Results
phase: 2
Announcement: results
Company: Actelion (Switzerland)
Product: cadazolid
Action mechanism: antibiotic. Cadazolid, a quinolonyl-oxazolidinone is a new chimeric antibiotic with structural elements of the oxazolidinone as well as the quinolone class of antibiotics. It is a strong inhibitor of Clostridium difficile protein synthesis leading to strong suppression of toxin and spore formation. In preclinical studies cadazolid showed potent in vitro activity against Clostridium difficile clinical isolates and in a human gut model of Clostridium difficile associated diarrhea (CDAD), while having only a very limited impact on bacteria of the normal gut microflora. In addition, cadazolid demonstrated a low propensity for resistance development.
Disease: Clostridium difficile associated diarrhea (CDAD)
Therapeutic area: Infectious diseases
Country:
Trial details: Cadazolid was studied in a multi-center, double-blind, randomized, active reference, parallel group, therapeutic exploratory dose-finding study. The study evaluated the efficacy, safety and tolerability of a 10-day, twice daily oral administration of 3 doses (250 mg, 500 mg or 1,000 mg b.i.d.) of cadazolid in patients with Clostridium difficile associated diarrhea (CDAD). As the current standard of care for CDAD, oral vancomycin (125 mg qid for 10 days) was used as the active reference. The study was completed in December of 2012, after having enrolled 84 patients. In CDAD, as in most acute infectious diseases, the clinically most relevant parameter for assessing treatment efficacy in a Phase II study is clinical response at the end of therapy (in this case principally resolution of diarrhea), which was evaluated at the Test-of-Cure visit (24 to 72 hours after the last dose of study treatment). In current and past clinical trials in CDAD, clinical cure rate is consistently selected as the primary endpoint. In CDAD, disease recurrence is an additional important parameter. Recurrence during the 4 weeks after the end of treatment is chosen as the main secondary endpoint.
Latest news: Actelion has decided to move forward with Phase III clinical development of cadazolid in patients suffering from Clostridium difficile associated diarrhea (CDAD). The decision is based on the results of a therapeutic exploratory Phase II dose-finding study randomizing 84 patients. The study evaluated the efficacy, safety and tolerability of 3 doses of cadazolid (administered orally, twice-daily) versus vancomycin, as an active reference, (125 mg administered orally, four times daily) for 10 days. The study, with a limited sample size, was not designed to compare statistically cadazolid versus vancomycin. The results of this Phase II study indicate that the effect of all doses of cadazolid are numerically similar to, or better than vancomycin on key endpoints including CDAD cure rates as well as sustained cure rates. Cure rate was defined as the resolution of diarrhea and no further need for CDAD therapy at test-of-cure 24 to 72 hours after the last dose of treatment, while sustained cure rate was defined as cured with no recurrence of diarrhea up to 4 weeks post-treatment. Recurrence rates were numerically lower for all doses of cadazolid as compared to vancomycin. Recurrence rate was defined as a new episode of diarrhea and a positive Clostridium difficile toxin test.Cadazolid was safe and well tolerated, at present no safety signals have been identified. Once full data analysis of this exploratory dose-finding study for cadazolid has been completed, Actelion will discuss the details of a Phase III program with Health Authorities. Actelion will present the results of this study through scientific presentations and publications.
