Study of S-033188 (Baloxavir Marboxil) Compared With Placebo or Oseltamivir in Patients With Influenza at High Risk of Influenza Complications

Inclusion Criteria

• Patients or their legal guardians who provide written informed consent to participate in the study on a voluntary basis. For adolescent patients, informed consent/assent of voluntary participation should be obtained in accordance with local requirements.
• Male or female patients ≥ 12 years at the time of signing the informed consent/assent form.
• Patients with a diagnosis of influenza confirmed by all of the following:
• Fever ≥ 38ºC (axillary) during the predose examinations or within the 4 hours prior if antipyretics were taken
• A positive rapid influenza diagnostic test (RIDT) result OR A patient with a negative RIDT may be enrolled if the patient reports contact with a known case of influenza within the prior 7 days and all other inclusion criteria are met.
• At least 1 each of the following general and respiratory symptoms associated with influenza is present with a severity of moderate or greater:

i. General symptoms (headache, feverishness or chills, muscle or joint pain, or fatigue) ii. Respiratory symptoms (cough, sore throat, or nasal congestion)

• The time interval between the onset of symptoms and the predose examinations is 48 hours or less. The onset of symptoms is defined as either:
• Time of the first increase in body temperature (an increase of at least 1ºC from normal body temperature)
• Time when the patient experiences at least 1 new general or respiratory symptom
• If a women of childbearing potential, agrees to use a highly effective method of contraception for 3 months after the first dose of study drug
• Patients will be considered at high risk* of influenza complications due to the presence of at least 1 of the following inclusion criteria:
• Asthma or chronic lung disease (such as chronic obstructive pulmonary disease or cystic fibrosis)
• Endocrine disorders (including diabetes mellitus)
• Residents of long-term care facilities (eg, nursing homes)
• Compromised immune system (including patients receiving corticosteroids not exceeding 20 mg of prednisolone or equivalent, and patients being treated for human immunodeficiency virus [HIV] infection with a CD4 count > 350 cells/mm³ within the last 6 months)
• Neurological and neurodevelopmental disorders (including disorders of the brain, spinal cord, peripheral nerve, and muscle, eg, cerebral palsy, epilepsy [seizure disorders], stroke, muscular dystrophy, or spinal cord injury)
• Heart disease (such as congenital heart disease, congestive heart failure, or coronary artery disease), excluding hypertension without any other heart-related symptoms
• Adults aged ≥ 65 years
• American Indians and Alaskan Natives
• Blood disorders (such as sickle cell disease)
• Metabolic disorders (such as inherited metabolic disorders and mitochondrial disorders)
• Morbid obesity (body mass index ≥ 40 kg/m²)
• Women who are within 2 weeks postpartum and are not breastfeeding

Exclusion Criteria

• Patients with severe influenza virus infection requiring inpatient treatment.
• Patients with known allergy to oseltamivir (Tamiflu®).
• Patients unable to swallow tablets or capsules.
• Patients who have previously received baloxavir marboxil.
• Patients weighing ≤ 40 kg.
• Patients who have been exposed to an investigational drug within 30 days prior to the predose examinations.
• Women who are pregnant, breastfeeding, or have a positive pregnancy test at the predose examinations. The following female patients who have documentation of either a or b below do not need to undergo a pregnancy test at the predose examinations:
• Postmenopausal women (defined as cessation of regular menstrual periods for 2 years or more and confirmed by a follicle-stimulating hormone test)
• Women who are surgically sterile by hysterectomy, bilateral oophorectomy, or tubal ligation
• Patients with concurrent infections at the predose examinations requiring systemic antimicrobial therapy.
• Patients with liver disease associated with