Laninamivir octanoate for post-exposure prophylaxis of influenza in household contacts: a randomized double blind placebo controlled trial

Abstract

Laninamivir octanoate, a long-acting neuraminidase inhibitor, is an effective treatment for influenza. However, its effectiveness for the prevention of influenza has not yet been demonstrated. We conducted a double-blind, multicenter, randomized, placebo-controlled trial to determine whether laninamivir octanoate was superior to a placebo for post-exposure prophylaxis of influenza in household contacts. Eligible participants, who were household members who did not have influenza and were in contact with an influenza-infected index patient, were randomly assigned (1:1:1) to one of three groups: 20 mg of laninamivir octanoate once daily for 2 days (LO-2), 20 mg of laninamivir octanoate once daily for 3 days (LO-3), or a placebo. The primary endpoint was the proportion of participants who developed clinical influenza during a 10-day period. A total of 1711 participants were enrolled, and 1451 participants were included in the primary analysis. The proportion of participants with clinical influenza was 3.9 % (19/487) in the LO-2 group, 3.7 % (18/486) in the LO-3 group, and 16.9 % (81/478) in the placebo group (P < 0.001 for each of the laninamivir octanoate group). The relative risk reductions, compared with the placebo group, were 77.0 % [95 % confidence interval (CI) 62.7-85.8] and 78.1 % (95 % CI 64.1-86.7 %) for the LO-2 and LO-3 groups, respectively. The incidences of adverse events in the laninamivir octanoate groups were similar to that in the placebo group. The inhalation of 20 mg of laninamivir octanoate once daily for 2 or 3 days was well tolerated and effectively prevented the development of influenza in household contacts.

Fig. 1

Participant flow chart. LO-2 20 mg of laninamivir octanoate administered once daily for 2 days; LO-3 20 mg of laninamivir octanoate administered once daily for 3 days; FAS the full analysis set, FASII the full analysis set index-infected, FASIINAB the full analysis set index-infected virus-negative at baseline. ^aOne participant who was allocated to the placebo group received 20 mg of laninamivir octanoate for 3 days. This participant was included in the originally allocated group in the full analysis set but was analyzed according to the actually administered treatment in the safety analysis set. A total of 1664 participants were included in the safety analysis set (552 participants in the LO-2 group, 553 in the LO-3 group, and 559 in the placebo group)

Fig. 2

Cumulative number of participants with clinical influenza according to observation day in the full analysis set index-infected virus-negative at baseline. LO-2 20 mg of laninamivir octanoate administered once daily for 2 days, LO-3 20 mg of laninamivir octanoate administered once daily for 3 days