E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
Influenza, commonly known as "the flu", is an infectious respiratory disease caused by influenza viruses. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022001 |
E.1.2 | Term | Influenza (epidemic) |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022003 |
E.1.2 | Term | Influenza B virus infection |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022002 |
E.1.2 | Term | Influenza A virus infection |
E.1.2 | System Organ Class | 100000004862 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10016790 |
E.1.2 | Term | Flu |
E.1.2 | System Organ Class | 100000004862 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
• To compare the safety of a single dose of baloxavir marboxil with 5 days of oseltamivir administered twice daily |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the PK of baloxavir marboxil and baloxavir after single dose of baloxavir marboxil • To evaluate the clinical efficacy of baloxavir marboxil compared with oseltamivir • To evaluate the antiviral activity of baloxavir marboxil compared with oseltamivir
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Aged 1 to < 12 years at randomization (Day 1) - Parent/guardian willing and able to comply with study requirements, in the investigator’s judgment - Patient able to comply with study requirements, depending on the patient’s level of understanding - Patient with a diagnosis of influenza virus infection confirmed by the presence of all of the following: ● Fever >=38 degrees C (tympanic temperature) at screening ● At least one respiratory symptom (either cough or nasal congestion) - The time interval between the onset of symptoms and screening is <= 48 hours (the onset of symptoms is defined as the time when body temperature first exceeded 37.5 degrees C if known, or the time when the first symptom was noticed by patient, parent or caregiver) |
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E.4 | Principal exclusion criteria |
- Severe symptoms of influenza virus infection requiring inpatient treatment - Concurrent infections requiring systemic antiviral therapy at screening - Require, in the opinion of the investigator, any of the prohibited medication during the study - Previous treatment with peramivir, laninamivir, oseltamivir, zanamivir, or amantadine within 2 weeks prior to screening - Immunization with a live/attenuated influenza vaccine in the 2 weeks prior to randomization - Concomitant treatment with steroids or other immuno-suppressant therapy - Known HIV infection or other immunosuppressive disorder - Uncontrolled renal, vascular, neurologic, or metabolic disease (e.g., diabetes, thyroid disorders, adrenal disease), hepatitis, cirrhosis, or pulmonary disease or patients with known chronic renal failure - Active cancer at any site - History of organ transplantation - Known allergy to either study drug (i.e., baloxavir marboxil and oseltamivir) or to acetaminophen - Females who have commenced menarche (i.e., child-bearing potential) - Participation in a clinical trial within 4 weeks or 5 half-lives of exposure to an investigational drug prior to screening, whichever is longer
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E.5 End points |
E.5.1 | Primary end point(s) |
Incidence, severity, and timing of adverse events, serious adverse events, vital sign measurements, and clinical laboratory test results |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
PK Endpoints 1. Plasma concentrations of baloxavir marboxil (pro-drug) and S-033447 (active metabolite) will be summarized by time (C24 and C72) and body weight 2. Area under the concentration-time curve from Time 0 to infinity (AUCinf) of baloxavir 3. Maximum plasma concentration (Cmax) of baloxavir 4. Time to maximum plasma concentration (Tmax) of baloxavir 5. Half-life (t1/2) of baloxavir Secondary efficacy Endpoints 6. Time to alleviation of influenza signs, symptoms 7. Time to return to normal health and activity 8. Duration of fever 9. Duration of symptoms 10. Frequency of influenza-related complications 11. Proportion of patients requiring antibiotics Virology Endpoints 12. Time to cessation of viral shedding by virus titer and by reverse transcriptase-polymerase chain reaction (RT-PCR) 13. Change from baseline in influenza virus titer and in the amount of virus RNA (RT-PCR) at each time point 14. Proportion of patients with positive influenza virus titer and proportion of patients positive by RT-PCR at each time point 15. Area under the curve in virus titer and in the amount of virus RNA (RT-PCR)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-5. Up to day 10 6-8. Days 1 to 15 9-15. Up to Day 29 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Costa Rica |
Israel |
Mexico |
Panama |
Poland |
South Africa |
Spain |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of this study is defined as the date when the last patient, last visit (LPLV) occurs or the date at which the last data point required for statistical analysis or safety follow-up is received from the last patient, whichever occurs later. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |