Efficacy and safety of intravenous peramivir for treatment of seasonal influenza virus infection

Abstract

Peramivir, a sialic acid analogue, is a selective inhibitor of neuraminidases produced by influenza A and B viruses. We evaluated the efficacy and safety of a single intravenous dose of peramivir in outpatients with uncomplicated seasonal influenza virus infection. A total of 300 previously healthy adult subjects aged 20 to 64 years with a positive influenza virus rapid antigen test were recruited within 48 h of the onset of influenza symptoms and randomized to three groups: single intravenous infusion of either 300 mg peramivir per kg of body weight, 600 mg peramivir, or matching placebo on study day 1. Influenza symptoms and body temperature were self-assessed for 14 days. Nasal and pharyngeal swabs were collected to determine the viral titer. The primary endpoint was the time to alleviation of symptoms. Of the 300 subjects, 296 were included in the intent-to-treat infected population (300 mg peramivir, n = 99; 600 mg peramivir, n = 97; and placebo, n = 100). Peramivir significantly reduced the time to alleviation of symptoms at both 300 mg (hazard ratio, 0.681) and 600 mg (hazard ratio, 0.666) compared with placebo (adjusted P value, 0.0092 for both comparisons). No serious adverse events were reported. Peramivir was well tolerated, and its adverse-event profile was similar to that of placebo. A single intravenous dose of peramivir is effective and well tolerated in subjects with uncomplicated seasonal influenza virus infection.

FIG. 1.

Study profiles.

FIG. 2.

Kaplan-Meier curve of time to alleviation of symptoms (intent-to-treat infected population). □, ○, and ⋄, censored subjects who withdrew before resolution of symptoms.

FIG. 3.

Proportions of subjects reporting normal temperature (intent-to-treat infected population). *, P < 0.05 between peramivir and placebo as determined by the Mantel-Haenszel test stratified for current smoking behavior and composite symptom scores at baseline.

FIG. 4.

(A) Means and SD of influenza virus titers (log₁₀ TCID₅₀/ml) over time (intent-to-treat infected population). Analysis was performed for observed data on the subset of subjects who were positive for influenza virus at baseline. Virus titers under the lower limit of quantification (1.1 log₁₀ TCID₅₀/ml) were set equal to 1.1. (B) Proportions of subjects showing positive viral titers (intent-to-treat infected population). Analysis was performed for observed data on the subset of subjects who were positive for influenza virus at baseline. The positive virus titer was at least 1.1 log₁₀ TCID₅₀/ml. *, P < 0.05 between peramivir and placebo as determined by the Mantel-Haenszel test, stratified by current smoking behavior and composite symptom scores at baseline.