LB-35. A Randomized, Double-Blind, Placebo (PCB) Controlled Study of Nitazoxanide (NTZ) in Adults and Adolescents with Acute Uncomplicated Influenza
Session: Oral Abstract Session: Late Breaker Oral Abstracts
Saturday, October 22, 2011: 6:30 PM
Room: 156ABC
Background: NTZ is currently in late stage development for the treatment of viral influenza. NTZ and the active metabolite tizoxanide inhibit the replication of multiple human and avian influenza viruses, including drug resistant strains. NTZ exhibits a high barrier to resistance; is synergistic with oseltamivir and zanamivir; and works via a novel mechanism. Studies indicate NTZ selectively targets the post-translational glycosylation of hemagglutinin without affecting neuraminidase. Phase II studies found NTZ to be effective in reducing the duration of symptoms associated with viral respiratory infections. The primary objective of this Phase III study is to demonstrate the efficacy of NTZ in reducing the time to resolution of clinical symptoms of influenza.

Method: 624 patients were enrolled at 74 outpatient study centers throughout the US. Eligibility criteria included: age 12 - 65 years, oral temperature ≥100.4 °F, at least one respiratory symptom and one constitutional symptom, symptom onset ≤48 hours of enrollment, laboratory confirmed influenza in the community, not at risk of influenza complications based on CDC criteria. Patients were randomized to receive NTZ 600 mg, NTZ 300 mg or PCB twice daily for 5 days and were followed for 28 days. Symptoms were graded (0 to 3, absent to severe) and recorded twice daily in a patient diary. Nasopharyngeal swabs collected at baseline and day 7 for all patients and on days 2, 3, 4 and 5 for a subset of patients subjected to PCR and culture to identify and quantify viruses. The primary endpoint was time to alleviation of symptoms (all symptoms absent or mild).

Result: The median time from first dose to alleviation of symptoms was significantly shorter for patients receiving NTZ 600 mg versus PCB (95 hrs vs 117 hrs, P=0.01). In addition, significant differences in changes in viral titer were observed within 24 hrs of initiating therapy. While the 300 mg dose group also showed improvements in clinical and virologic endpoints, these did not reach statistical significance. Adverse events were similar between the groups.

Conclusion: These data indicate NTZ is safe and effective in reducing the duration of symptoms associated with influenza while reducing the intensity of the influenza virus. Further studies are warranted.


Subject Category: V. Virology including clinical and basic studies of viral infections, including hepatitis

Jean-Francois Rossignol, MD, FRCPath, PhD, FRSC1,2,3, Sreedhar Samudrala, MD4, Melanie Hoppers, MD5, Jason Haffizulla, MD6, Harvey Resnick, MD7, Aaron Hartman, MD8, Stefan Comhaire9, Maria Carrion, MD1 and Matthew Bardin, PharmD, BCPS1, (1)Romark Institute for Medical Research, Tampa, FL, (2)Department of Biochemistry, Oxford University, Glycobiology Institute, Oxford, United Kingdom, (3)Stanford University Medical Center, Palo Alto, CA, (4)HCCA Clinical Research Solutions, Franklin , TN, (5)HCCA Clinical Research Solutions - Jackson, Jackson, TN, (6)Sunrise Medical Research, Lauderdale Lakes, FL, (7)RD Clinical Research, Inc., Lake Jackson, TX, (8)Virginia Research Center, Midlothian, VA, (9)SGS Life Science Services Clinical Research, Gaithersburg, MD

Disclosures:

J. F. Rossignol, Romark Laboratories: Board Member, Employee and Shareholder, Licensing agreement or royalty and Salary

S. Samudrala, Romark Laboratories: Research Contractor, Research support

M. Hoppers, Romark Laboratories: Research Contractor, Research support

J. Haffizulla, Romark Laboratories: Research Contractor, Research support

H. Resnick, Romark Laboratories: Research Contractor, Research support

A. Hartman, Romark Laboratories: Research Contractor, Research support

S. Comhaire, Romark Laboratories: Research Contractor, Research support

M. Carrion, Romark Laboratories: Employee, Salary

M. Bardin, Romark Laboratories: Employee, Salary

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.