Long-acting Neuraminidase Inhibitor Laninamivir Octanoate as Post-exposure Prophylaxis for Influenza

Abstract

Background: A single administration of laninamivir octanoate, a long-acting neuraminidase inhibitor, has been proven to be effective in the treatment of influenza but not for post-exposure prophylaxis.

Methods: We conducted a double-blind, multicenter, randomized, placebo-controlled study to determine if a single administration of laninamivir octanoate 40 mg was superior to placebo for post-exposure prophylaxis. Eligible participants who had cohabited with an influenza patient within 48 hours of symptom onset were randomly assigned (1:1:1) to 1 of 3 groups: 40 mg of laninamivir octanoate single administration (LO-40SD), 20 mg of laninamivir octanoate once daily for 2 days (LO-20TD), or placebo. The primary efficacy endpoint was the proportion of participants who developed clinical influenza (defined as influenza virus positive, an axillary temperature >37.5°C, and at least 2 symptoms) over a 10-day period.

Results: A total of 803 participants were enrolled, with 801 included in the primary analysis. The proportions of participants with clinical influenza were 4.5% (12/267), 4.5% (13/269), and 12.1% (32/265) in the LO-40SD, LO-20TD, and placebo groups, respectively. A single administration of laninamivir octanoate 40 mg significantly reduced the development of influenza compared with placebo (P = .001). The relative risk reductions compared with the placebo group were 62.8% and 63.1% for the LO-40SD and LO-20TD groups, respectively. The incidence of adverse events in the LO-40SD group was similar to that of the LO-20TD and placebo groups.

Conclusions: A single administration of laninamivir octanoate was effective and well tolerated as post-exposure prophylaxis to prevent the development of influenza.

Clinical trials registration: JapicCTI-142679.

Keywords: influenza; laninamivir; neuraminidase inhibitor; post-exposure; prophylaxis.

Figure 1.

Participant flow chart. A total of 801 participants were included in the safety analysis set (267 participants in the LO-40SD group, 269 in the LO-20TD group, and 265 in the placebo group). More than 1 participant could be enrolled for each index patient. In this case, the index patient was counted once for each household contact who was enrolled. In fact, 687 index patients (the full analysis set [FAS]) were enrolled. Abbreviations: FASII, the full analysis set, index-infected; FASIINAB, the full analysis set, index-infected virus-negative at baseline; LO-20TD, 20 mg of laninamivir octanoate administered once daily for 2 days; LO-40SD, 40 mg of laninamivir octanoate, single administration.

Figure 2.

Cumulative number of participants with clinical influenza, the primary endpoint, according to observation day. A, The cumulative number of participants with clinical influenza, the primary endpoint, by observation day in the full analysis set (FAS). B, The cumulative number of participants with clinical influenza, the primary endpoint, by observation day in the FAS index-infected virus-negative at baseline set (FASIINAB). Abbreviations: LO-20TD, 20 mg of laninamivir octanoate administered once daily for 2 days; LO-40SD, 40 mg of laninamivir octanoate, single administration.