Ridinilazole, a new antibiotic for treatment of Clostridium difficile infection (CDI) proved noninferior to vancomycin, showing promise especially in lower recurrence risk, according to a study funded in part by ridinilazole manufacturer Summit Therapeutics.
In a phase 2, 1:1 randomized, double-blind trial of 69 CDI patients, 24 of 36 (66.7%) ridinilazole patients reported a sustained clinical response, compared with 14 of 33 vancomycin patients (42.4%), indicating statistical noninferiority – and even superiority at the upper confidence level – of ridinilazole (Lancet Infect Dis. 2017 Apr 28.).
Over the course of 10 days, investigators gave the ridinilazole group 200 mg orally twice per day, as well as two placebo doses. Those in the vancomycin group took 125 mg orally four times per day.
Investigators assessed both groups on days 4-6, 10-11, 12-14, and routine weekly follow-ups until 30 days after treatment.
Most of the patients were white females, with an average age of 58 years for the ridinilazole group, and 56 years for the vancomycin group.
Ridinilazole correlated with more sustained clinical responses across almost all subgroups as well, including with treatment differences (respectively) of 42.7%, 15.9%, 19.9%, and 8.9% for those over 75 years, with a more severe diagnosis, more than one previous CDI episode, and those taking other antibiotics before study participation, according to the investigators. Both groups saw similar rates of adverse events related to treatment.
The outcome of this trial could be significant in reducing recurrence risk in CDI patients, which occurs in up to 30% of patients after first treatment, and can increase up to 65% after multiple reinfections, according to Richard Vickers, PhD, chief scientific officer on antimicrobials at Summit Therapeutics PLC, and his fellow investigators.
CDI patients also are subject to significantly higher inpatient mortality, spend longer periods in intensive care, and have higher rates of all-cause readmission over 3 months than do matched controls, the investigators noted.
Unlike the three common CDI drugs on the market, metronidazole, vancomycin, and fidaxomicin, ridinilazole is restricted to the gastrointestinal tract and, according to the investigators, has shown encouraging results in previous studies.
“In vitro studies have shown its high inhibitory activity against C. difficile and minimal activity against both Gram-positive and Gram-negative aerobic and anaerobic intestinal microorganisms,” they wrote. “In a phase 1 study, ridinilazole was safe and well tolerated in healthy human volunteers, with little systemic absorption and little effect on normal gut microbiota.”
They asserted it was this lack of effect that caused the drug to show success in phase 2, noting ridinilazole’s superiority was “likely to be due to the highly selective activity of ridinilazole against CDI and the absence of collateral damage to the microbiota during therapy.”
The study was limited by its sample, which was younger and had a milder form of CDI than is usually represented. The study also formed its power calculations based on the original sample size of 100, and not the adjusted, intended-to-treat population of 69 which became its primary analysis.
Finally, the investigators advised further trials be conducted with a follow-up schedule longer than 30 days.
Dr. Vickers, Dr. Bina Tejura, and Dr. David Roblin reported working for Summit Therapeutics, the drug manufacturer, and hold share options with the company. Other authors reported holding close relationships with other, similar drug manufacturing companies.