Long-Acting Neuraminidase Inhibitor Laninamivir Octanoate versus Oseltamivir for Treatment of Influenza: A Double-Blind, Randomized, Noninferiority Clinical Trial

• Published in: Clinical infectious diseases Vol. 51; no. 10; pp. 1167 - 1175
• Main Authors: Watanabe, Akira, Chang, Shan-Chwen, Kim, Min Ja, Chu, Daniel Wai-sing, Ohashi, Yasuo
• Format: Journal Article
• Language: English
• Published: Oxford The University of Chicago Press 15.11.2010; University of Chicago Press; Oxford University Press
• Subjects: Administration, Inhalation; Administration, Oral; Adult; Aged; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Antiviral Agents - administration & dosage; ARTICLES AND COMMENTARIES; Biological and medical sciences; Caprylates; Clinical outcomes; Clinical trials; Diseases; Dosage; Drug Administration Schedule; Drug therapy; Female; H1N1 subtype influenza A virus; Human viral diseases; Humans; Infections; Infectious diseases; Influenza; Influenza A virus; Influenza A Virus, H1N1 Subtype - isolation & purification; Influenza A Virus, H3N2 Subtype - isolation & purification; Influenza B virus - isolation & purification; Influenza, Human - drug therapy; Influenza, Human - virology; Inhalation; Inhibitor drugs; Male; Medical sciences; Middle Aged; Orthomyxoviridae; Oseltamivir - administration & dosage; Pharmacology. Drug treatments; Symptoms; Viral diseases; Viral diseases of the respiratory system and ent viral diseases; Viral Load; Viruses; Zanamivir - administration & dosage; Zanamivir - analogs & derivatives; Long acting; Neuraminidase inhibitor; Enzyme; Enzyme inhibitor; Glycosylases; Infection; Oseltamivir; Treatment; Glycosidases; Viral disease; Exo-α-sialidase; Hydrolases; Antiviral; Clinical trial; Influenza A; Comparative study
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/656802

Background. A single administration of laninamivir octanoate, a long-acting neuraminidase inhibitor, against influenza infection has been proven effective in nonclinical studies. This study evaluated the clinical efficacy of laninamivir octanoate for the treatment of adult influenza patients. Methods. A double-blind, randomized controlled trial examined whether laninamivir octanoate was noninferior to oseltamivir. A total of 1003 patients aged ⩾20 years with febrile influenza symptoms for no more than 36 h were randomized to receive either 40 mg of laninamivir octanoate, 20 mg of laninamivir octanoate, or oseltamivir. Laninamivir octanoate was inhaled once on day 1, and oseltamivir (75 mg) was administered orally twice daily for 5 days. The primary end point was the time to illness alleviation. Results. A total of 996 patients were included in the primary analysis (40-mg laninamivir octanoate, n= 334; 20-mg laninamivir octanoate, n=326; and oseltamivir, n=336). The median time to illness alleviation in the 40-mg laninamivir octanoate, 20-mg laninamivir octanoate, and oseltamivir groups was 73.0, 85.8, and 73.6 h, respectively. The difference between laninamivir octanoate and oseltamivir was −0.6 h (95% confidence interval, −9.9 to 6.9 h) for the 40-mg group and 12.2 h (95% confidence interval, −1.5 to 17.2 h) for the 20-mg group. The upper limits of the 95% confidence intervals were less than the prespecified noninferiority margin (18 h). The proportion of patients shedding virus at day 3 was significantly lower in the 40-mg laninamivir octanoate group than in the oseltamivir group (P=.006). Conclusions. A single inhalation of laninamivir octanoate is effective for the treatment of seasonal influenza, including that caused by oseltamivir-resistant virus, in adults. Clinical trials registration. NCT00803595.