Influsplit Tetra vaccine produced by investigational process

Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of the specified solicited local symptom regardless of its intensity. Grade 3 pain = significant pain at rest and pain that prevented normal everyday activities. Grade 3 redness and swelling = greater than 100 millimeters (mm) i.e. \>100mm.

Solicited general symptoms assessed were fatigue,gastrointestinal symptoms, headache, Joint Pain, myalgia, shivering and fever. Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain. Any was defined as any solicited general symptom reported irrespective of intensity and relationship to vaccination. Grade 3 was defined as symptoms that prevented normal activities. Related was defined as symptoms assessed by the investigator to have a causal relationship to vaccination. Any fever was defined as subjects with a documented temperature of greater than or equal to (≥) 38°C/100.4°F by any route and all subjects reporting temperature less than (\< )38°C but with missing values (MC) for at least one day during the solicited period. Grade 3 fever was defined as temperature ≥39.0°C.

Duration was defined as number of days with any grade of local and general symptoms.

Oculorespiratory syndrome (ORS) was defined as the occurrence within 24 hours after vaccination of one or more of the following newly onset symptoms: bilateral red eyes, cough, wheeze, chest tightness, difficulty breathing, difficulty swallowing, hoarseness, sore throat, facial swelling. Any was defined as any ORS symptom regardless of intensity grade or relationship to vaccination. Grade 3 ORS was defined as ORS symptoms that prevented normal activities. Related ORS was defined as ORS symptom(s) assessed by the investigator as causally related to the vaccination.

MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Any was defined as any occurrence of MAE(s). Grade 3 was defined as MAE that prevented normal activities. Related was defined as MAE assessed by the investigator to be causally related to the study vaccination.

Solicited local symptoms assessed were pain, redness and swelling. Any = occurrence of the specified solicited local symptom regardless of its intensity. Grade 3 pain = Cried when limb was moved/spontaneously painful. Grade 3 redness and swelling = greater than 50 millimeters (mm) i.e. \>50mm.

Solicited general symptoms assessed were drowsiness, irritability/fussiness, loss of appetite and fever. Any was defined as any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related was defined as symptoms assessed by the investigator to have a causal relationship to vaccination. Grade 3 irritability/fussiness was defined as crying that could not be comforted/prevented normal activity. Grade 3 loss of appetite was defined as not eating at all. Grade 3 drowsiness was defined as drowsiness that prevented normal activity. Any fever was defined as subjects with a documented temperature of greater than or equal to (≥) 38°C/100.4°F by any route and all subjects reporting temperature less than (\< )38°C but with missing values (MC) for at least one day during the solicited period. Grade 3 fever was defined as temperature greater than (\>) 39.0°C.

Solicited general symptoms assessed were fatigue, gastrointestinal symptoms, headache, joint pain, myalgia, shivering and fever (Fever = temperature above 38.0 degrees Celsius (°C)). Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain. Any = any solicited general symptom reported irrespective of intensity and relationship to vaccination. Related = symptoms considered by the investigator to have a causal relationship to vaccination. Grade 3 symptoms = symptoms that prevented normal activity. Any fever = all subjects with a documented temperature of ≥ 38°C/100.4°F by any route and all subjects reporting temperature \< 38°C but with missing values (MC) for at least one day during the solicited period. Grade 3 fever = temperature above 39.0°C.

Duration was defined as number of days with any grade of local symptoms.

Duration was defined as number of days with any grade of general symptoms.

Duration was defined as number of days with any grade of general symptoms.

Oculorespiratory syndrome (ORS) was defined as the occurrence within 24 hours after vaccination of one or more of the following newly onset symptoms: bilateral red eyes, cough, wheeze, chest tightness, difficulty breathing, difficulty swallowing, hoarseness, sore throat, facial swelling. Any = occurrence of any ORS symptom regardless of intensity grade or relationship to vaccination. Grade 3 = ORS symptoms that prevented normal activities. Related = ORS symptom assessed by the investigator as causally related to the vaccination.

MAEs were defined as adverse events with medically-attended visits that were not routine visits for physical examination or vaccination, such as visits for hospitalization, an emergency room visit, or an otherwise unscheduled visit to or from medical personnel (medical doctor) for any reason. Any was defined as any occurrence of MAE(s). Grade 3 was a MAE that prevented normal activities. Related was defined as a MAE assessed by the investigator to be causally related to the study vaccination.

An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.

An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as occurrence of any unsolicited symptom regardless of intensity grade or relation to vaccination.

Any fever = all subjects with a documented temperature of ≥ 38°C/100.4°F by any route and all subjects reporting temperature \< 38°C but with missing values (MC) for at least one day during the solicited period.

A serious adverse event was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.

A serious adverse event was defined as any untoward medical occurrence that: resulted in death, was life threatening, required hospitalization or prolongation of hospitalization, resulted in disability/incapacity or was a congenital anomaly/birth defect in the offspring of a study subject. Any was defined as occurrence of any symptom regardless of intensity grade or relation to vaccination and related was an event assessed by the investigator as causally related to the study vaccination.

HI antibody titres were expressed as geometric mean titers (GMTs) and adjusted GMT ratios. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), FluA/Texas/50/2012 (H3N2), Flu B/Massachusetts/02/2012 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).

HI antibody titres were expressed as geometric mean titers (GMTs) and adjusted GMT ratios. The vaccine strains assessed were Flu A/Christchurch/16/2010 (H1N1), FluA/Texas/50/2012 (H3N2), Flu B/Massachusetts/02/2012 (Yamagata) and Flu B/Brisbane/60/2008 (Victoria).