Program Schedule

LB-8
A Safety and Pharmacokinetic Study of Fidaxomicin in Children with Clostridium difficile-associated diarrhea

Session: Oral Abstract Session: Late Breaker Oral Abstracts
Saturday, October 11, 2014: 11:40 AM
Room: The Pennsylvania Convention Center: 105-AB
Background: DIFICID (Fidaxomicin, FDX) has been approved in multiple countries for the treatment of C. difficile-associated diarrhea (CDAD) in adults. This is the first study of fidaxomicin in pediatric patients.

Method: This open-label study enrolled children, ages 6 mo to <18 yr, with diarrhea + positive toxin. Subjects were treated with FDX for 10 days with 32 mg/kg /day (up to 200 mg BID, the adult dose), as either the commercial tablet or an oral suspension. Plasma samples for drug concentration measurement were collected pre-dose and at two timepoints post-dose between days 5-10. Fecal samples were collected on the last day of therapy. Safety was assessed via adverse events, clinical labs, ECGs, physical exams including vital signs. Efficacy was also monitored.

Result: 38 subjects, range 11 mo to 17 yr of age, were enrolled and treated. Most had relatively complex medical histories, including neoplasms (23.7%) and gastrointestinal disorders (78.9%). Plasma concentrations were generally in the low ng/mL range, with a mean FDX concentration across the strata that ranged from 8.87 to 16.6 ng/mL and metabolite OP-1118 that ranged from 27.5 to 130 ng/mL at 1-2 hours post-dose, with no age-related trends. Fecal FDX concentrations averaged 3230 µg/g, with a trend toward higher concentrations in the youngest age group. 73.7% of subjects had at least one adverse event, with most adverse events being mild (44.7%) to moderate  (21.1%) in severity and were of the nature expected for a pediatric population with moderate to severe underlying illnesses. 9 subjects had SAEs, none of which were considered related to FDX.  Clinical response rates were high (92.1% overall). 28.6% of the subjects with a clinical response recurred; of these, all but one had a history of recurrent CDAD.

Conclusion: Fidaxomicin treatment in children with CDAD was well tolerated, and had a pharmacokinetic profile that was similar to that reported in adults, with low plasma levels and high fecal concentrations. Clinical response was excellent, and while a higher percentage of children experienced a recurrence than observed in prior adult studies, this is likely reflective of the high number of subjects enrolling with prior episodes of CDAD.

Pam Sears, PhD, Cubist Pharmaceuticals, San Diego, CA, Sheldon L. Kaplan, MD, FIDSA, Pediatrics, Baylor College of Medicine and Texas Children's Hospital, Houston, TX, Marian Michaels, MD, Pediatric Infectious Diseases, Children's Hospital of Pittsburgh, Pittsburgh, PA, Shawn Flanagan, Cubist, San Diego, CA and Molly O'gorman, MD, Primary Children's Medical Center, Salt Lake City, UT

Disclosures:

P. Sears, Cubist Pharmaceuticals: Employee, Salary

S. L. Kaplan, Cubist Pharmaceuticals: Investigator, Investigator fees

M. Michaels, Cubist Pharmaceuticals: Investigator, Investigator fees

S. Flanagan, Cubist: Employee and Shareholder, Salary

M. O'gorman, Cubist Pharmaceuticals: Investigator, Investigator fees

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