A Study of S-033188 (Baloxavir Marboxil) Compared With Placebo or Oseltamivir in Otherwise Healthy Patients With Influenza
Condition: Influenza
MeSH terms: Influenza, Human
Intervention: Baloxavir Marboxil; Placebo to Baloxavir Marboxil; Oseltamivir; Placebo to Oseltamivir
Intervention description: 2 to4 X 20-mg tablets taken orally; 2 to4 X 20-mg tablets taken orally; 75 mg capsules taken orally; Placebo capsules matching oseltamivir 75 mg capsules
Intervention MeSH terms: Oseltamivir; Baloxavir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 1436.0
Sex: All
Minimum age: 12 Years
Maximum age: 64 Years
Healthy volunteers: No
Keywords: Flu; Baloxavir Marboxil; Oseltamivir; Tamiflu®

Summary:

      The primary objective of this study is to evaluate the efficacy of a single, oral dose of
      baloxavir marboxil compared with placebo by measuring the time to alleviation of symptoms in
      patients with uncomplicated influenza virus infection.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients who are able to understand the study and comply with all study procedures,
             and willing to provide written informed consent/assent prior to the predose
             examinations appropriately. As for adolescent patients, informed consent/assent of
             voluntary participation should be obtained in accordance with local requirements

          2. Male or female patients aged ≥ 12 to ≤ 64 years at the time of signing the informed
             consent/assent form.

          3. Patients with a diagnosis of influenza virus infection confirmed by all of the
             following:

               1. Fever ≥ 38ºC (axillary) in the predose examinations or > 4 hours after dosing of
                  antipyretics if they were taken

               2. At least one of the following general systemic symptoms associated with influenza
                  are present with a severity of moderate or greater

                    -  Headache

                    -  Feverishness or chills

                    -  Muscle or joint pain

                    -  Fatigue

               3. At least one of the following respiratory symptoms associated with influenza are
                  present with a severity of moderate or greater

                    -  Cough

                    -  Sore throat

                    -  Nasal congestion

          4. 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:

               1. Time of the first increase in body temperature (an increase of at least 1ºC from
                  normal body temperature)

               2. Time when the patient experiences at least one general or respiratory symptom

          5. Women of childbearing potential who agree to use a highly effective method of
             contraception for 3 months after the first dose of study drug

        Exclusion Criteria:

          1. Patients with severe influenza virus infection requiring inpatient treatment.

          2. Patients aged ≥ 20 years with known allergy to oseltamivir (Tamiflu®).

          3. Patients with any of the following risk factors

               1. Women who are pregnant or within 2 weeks post-partum

               2. Residents of long-term care facilities (eg, welfare facilities for the elderly,
                  nursing homes)

               3. Chronic respiratory diseases including bronchial asthma

               4. Neurological and neurodevelopmental disorders including disorders of the brain,
                  spinal cord, peripheral nerve, and muscle (eg, cerebral palsy, epilepsy [seizure
                  disorders], stroke, intellectual disability, moderate to severe developmental
                  delay, muscular dystrophy, or spinal cord injury)

               5. Heart disease (such as congenital heart disease, congestive heart failure, or
                  coronary artery disease), excluding hypertension without any other heart-related
                  symptoms)

               6. American Indians and Alaskan natives

               7. Blood disorders (such as sickle cell disease)

               8. Endocrine disorders (including diabetes mellitus)

               9. Kidney disorders

              10. Liver disorders

              11. Metabolic disorders

              12. Compromised immune system (including patients receiving immunosuppressant
                  therapy, or those with cancer or human immunodeficiency virus [HIV] infection)

              13. Morbid obesity (body mass index [BMI] ≥ 40)

          4. Patients unable to swallow tablets or capsules.

          5. Patients who have previously received Baloxavir Marboxil.

          6. Patients weighing < 40 kg

          7. Patients who have been exposed to an investigational drug within 30 days prior to the
             predose examinations.

          8. Women who are breastfeeding or have a positive pregnancy test in the predose
             examinations. The following female patients who have documentation of either a or b
             below do not need to undergo a pregnancy test in the predose examinations:

               1. Postmenopausal (defined as cessation of regular menstrual periods for 2 years or
                  more and confirmed by a follicle-stimulating hormone test) women

               2. Women who are surgically sterile by hysterectomy, bilateral oophorectomy, or
                  tubal ligation

          9. Patients with concurrent infections requiring systemic antimicrobial and/or antiviral
             therapy at the predose examinations.

         10. Patients who have received peramivir, laninamivir, oseltamivir, zanamivir,
             rimantadine, umifenovir, or amantadine within 30 days prior to the predose
             examinations.

         11. Patients who have received an investigational monoclonal antibody for a viral disease
             in the last year.

         12. Patients with severe underlying diseases.

         13. Patients with known creatinine clearance ≤ 60 mL/min.

         14. Patients who, in the opinion of the investigator, would be unlikely to comply with
             required study visits, self-assessments, and interventions