PE‐01.

Methods	A double‐blind, double‐dummy, randomised, placebo‐controlled, parallel group, multicentre study to investigate the efficacy and safety of oral and inhaled GG167 in reducing the development of influenza symptoms
Participants	Inclusion criteria: Index case: Individuals who the investigator diagnosed as having symptoms of influenza A and B by the following criteria: individuals who satisfied the following conditions for influenza infection between the commencement of the symptoms and the first presentation to the participating centre, were willing to participate in the study and could be expected to follow the investigator's orders: Participants with feverishness or a temperature of 37.5 °C or greater at the first presentation At least 2 of the following: headache, muscle pain, sore throat, cough Contact: Person who had any following chance of contact with an index case within 4 days after the commencement of influenza symptoms of the index case and was diagnosed that he/she may be infected with influenza: Sleeping in the same room as the index case (such as inpatients) Working in the same room as the index case (such as co‐workers) Living in the same home as the index case (such as family) Participants had to be at least 16 years old, understand how to use the investigational agents and intend to co‐operate with the study and could be expected to follow the investigator's orders Exclusion criteria: Person who had feverishness within 48 hours prior to the first presentation day or a temperature 37.0 °C or more at the first presentation day Person who had 2 or more symptoms of the following symptoms within 48 hours prior to the first presentation day: headache, muscle pain, sore throat, cough, nasal symptoms and general fatigue Person who had at least 1 of the following symptoms of "score 2" or more: headache, muscle pain, sore throat, cough, nasal symptoms and general fatigue Person suspected of having a bacterial infection Patient with an unstable chronic disease Pregnancy or suspicion of pregnancy as well as person planning to become pregnant during the course of the study and nursing mothers Patient who was prescribed any investigational medication within the last 3 months Patient who received influenza vaccine within the last 1 year Any patient the investigator determines to be inappropriate for the study Definition of patient populations for analysis ITT population N = 44 (IH 11, IN 11, IH + IN 11 and PL 11) Protocol compatible population: N = 40 (IH9, IN 11, IH + IN 10, PL 10) Safety population: N = 44 (IH 11, IN 11, IH + IN 11 and PL 11) Safety outcome The safety measure was the incidence of abnormal symptoms/abnormal laboratory changes in which causality determinations were not completely denied. "Abnormal symptoms or abnormal laboratory findings" are the adverse events defined as newly observed or remarkably worsened symptoms after treatment started or clinically untoward abnormal or abnormally changed laboratory findings after treatment started irrespective of the causal assessment
Interventions	Orally inhaled zanamivir 10 mg + intranasally nebulised placebo Orally inhaled placebo + intranasally nebulised zanamivir 6.4 mg Orally inhaled zanamivir 10 mg + intranasally nebulised zanamivir 6.4 mg Orally inhaled placebo + intranasally nebulised placebo
Outcomes	Primary: the proportion of subjects who, during prophylaxis (day 1 to day 5), developed symptomatic influenza Secondary: The proportion of subjects who, during prophylaxis (day 6 to day 10), developed symptomatic influenza The proportion of subjects who, during prophylaxis (day 1 to day 10), developed symptomatic influenza The number and proportion of subjects who, during prophylaxis (day 1 to day 5 or day 6 to day 10), developed symptomatic influenza
Notes	—
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Method of sequence generation not specified
Allocation concealment (selection bias)	High risk	Not described
Incomplete outcome data (attrition bias) Symptoms	High risk	The trial was terminated prematurely
Incomplete outcome data (attrition bias) Complications of influenza	High risk	The trial was terminated prematurely
Incomplete outcome data (attrition bias) Safety data	High risk	The trial was terminated prematurely
Selective reporting (reporting bias)	High risk	Analysis, including primary outcomes, was planned after study unblinding
Other bias	High risk	Under‐recruitment
Blinding of participants and personnel (performance bias) All outcomes	High risk	No certificate of analysis
Blinding of outcome assessment (detection bias) All outcomes	High risk	Not described