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 |
Simple influenza infection. |
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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 | 17.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060078 |
E.1.2 | Term | Influenza serology positive |
E.1.2 | System Organ Class | 100000004848 |
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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 |
The primary objective of the study is to evaluate the clinical efficacy of favipiravir compared with placebo in treating adult subjects who have confirmed influenza. |
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E.2.2 | Secondary objectives of the trial |
• To further evaluate the clinical and anti-viral effects of favipiravir.
• To evaluate the safety of favipiravir in adult subjects with symptoms consistent with uncomplicated influenza.
• To characterize the PK of favipiravir when used under clinical conditions.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Understands the requirements of the study and provides written informed consent prior to undergoing any study-related procedures.
2. Is an adult male or female between the ages of 18 and 80 years old,inclusive (or according to national standards in each country).
3. Has 2 or more of the following symptoms (moderate to severe in intensity) at the time of enrollment that began 48 hours or less prior to the first dose of study medication:
a. Cough
b. Sore throat
c. Headache
d. Nasal congestion
e. Body aches and pains
f. Fatigue
4. Has a fever at the first visit or in the 6 hours prior if antipyretics were taken, defined as
a. ≥ 38.0°C (≥ 100.4°F) for subjects < 65 years old; or
b. ≥ 37.8°C (≥ 100.0°F) for subjects ≥ 65 years old.
5. Tests positive for influenza A or B during the 48 hours between onset of symptoms and anticipated dosing with study medication
a. Confirmed at the site by a Rapid Antigen Test (RAT) provided for the study or real time polymerase chain reaction (PCR) OR
b. Confirmed by diagnostic assay (e.g. non-study RAT or PCR) from another clinic OR
c. A subject testing negative by RAT may still be enrolled if the Medical Monitor and Investigator agree that there is a known influenza outbreak circulating in the community or the subject has been in close contact with a person who was recently confirmed to have influenza by RAT or another laboratory test.
6. If male, subject must:
a. Be sterile (e.g., have had a vasectomy at least 6 months prior to Day 1 dosing) OR
b. Agree he will not donate sperm during the study and for 3 months following the last dose of study medication, AND
c. Will strictly adhere to the following contraceptive measures during the study and for 3 months following the last dose of study medication:
i. Abstain from sexual intercourse OR
ii. Use a condom during sexual intercourse with a female of child-bearing potential. In addition, the female partner must use another form of contraception (e.g. intrauterine device [IUD], diaphragm with spermicide, oral contraceptives, injectable progesterone, or subdermal implants).
iii. The final decision of effective contraception will be made in accordance with local regulations.
7. If female, subject must:
a. Be unable to bear children (have not had a period for ≥ 12 consecutive months, have had her uterus or ovaries removed, or have had a tubal ligation) OR
b. Have a male partner incapable of fathering a child (e.g., has had a vasectomy at least 6 months prior to study entry) OR
c. Have a negative pregnancy test at Screening AND
d. Not have had unprotected sex within the last month or used a medically approved method of contraception within the last month AND
e. If she is of childbearing potential, will strictly adhere to the following contraceptive measures during the study and for 3 months following the last dose of study medication:
i. Abstain from sexual intercourse OR
ii. Her male partner agrees to use a condom during sexual intercourse AND
iii. Agree to use an approved method of contraception (e.g., IUD, diaphragm with spermicide, oral contraceptives, injectable progesterone, or subdermal implants).
iv. The final decision of effective contraception will be made in accordance with local regulations.
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E.4 | Principal exclusion criteria |
1. Female subjects who are pregnant, currently breast-feeding, or have a positive pregnancy test at Screening.
2. Has taken an anti-influenza drug (e.g., amantadine hydrochloride, rimantadine, oseltamivir phosphate, zanamivir hydrate, peramivir or other) within 4 weeks prior to signing the informed consent.
3. Has received any live attenuated influenza vaccine within 4 weeks prior to signing the informed consent.
4. Has underlying chronic respiratory disease (e.g., chronic obstructive pulmonary disease [COPD], chronic bronchitis, diffuse panbronchiolitis, bronchiectasis, pulmonary emphysema, pulmonary fibrosis, or active tuberculosis). Subjects with bronchial asthma will be excluded from the study if they presently experience asthma symptoms, are currently requiring treatment, or have had an asthma attack in the past year.
5. At the beginning of the study, is suspected of having bacterial respiratory infection (i.e., expectoration of purulent or mucopurulent sputum and/or infiltrate in lung observed on chest x ray, or is on antibiotics for pulmonary disease).
6. Has a history of gout or is under treatment for gout or hyperuricemia.
7. Has hereditary xanthinuria.
8. Has a history of hypouricemia (under 1 mg/dL) or xanthine calculi of the urinary tract.
9. Has a history of hypersensitivity to an anti-viral nucleoside-analog drug targeting a viral RNA polymerase.
10. Is using adrenocorticosteroids (except topical preparation) or immunosuppressive drugs (e.g., immunosuppressants, anticancer drugs).
11. Has an allergy to acetaminophen (paracetamol) or has a contraindication for acetaminophen (paracetamol).
12. Has a serious chronic disease (e.g., human immunodeficiency virus [HIV], cancer requiring chemotherapy within the preceding 6 months, moderate or severe hepatic insufficiency and/or unstable renal, cardiac, pulmonary, neurologic, vascular, or endocrinologic disease states requiring medication dose adjustments within the last 30 days).
13. Has previously received favipiravir (T-705a).
14. Has renal insufficiency requiring hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).
15. Has a history of alcohol or drug abuse in the preceding 2 years.
16. Has a psychiatric disease that is not well controlled (not on a stable regimen for greater than one year).
17. Has taken another investigational drug within 30 days prior to signing the informed consent.
18. Is deemed by the Investigator to be ineligible for any reason.
19. Is employed by or is related to an employee of the clinical study site.
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E.5 End points |
E.5.1 | Primary end point(s) |
Time from the start of study treatment until alleviation of all primary influenza symptoms (i.e. cough, sore throat, headache, nasal congestion, body aches and pains, fatigue) and to resolution of fever by temperature (oral) measurements to be < 38.0°C (< 100.4°F) for subjects < 65 years old and < 37.8°C (< 100.0°F) for subjects ≥ 65 years old. |
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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) |
• Time from the start of study treatment until alleviation of each of the following influenza symptoms (cough, sore throat, headache, nasal congestion, body aches and pains, and fatigue)
• Time from the start of study treatment until resolution of fever by temperature (oral) to be < 38.0°C (<100.4°F) for subjects < 65 years old and < 37.8°C (<100.0°F) for subjects ≥ 65 years old
• Changes in log-transformed viral load as measured by quantitative polymerase chain reaction (qPCR) and in the determination of median tissue culture infective dose (TCID50), from nasopharyngeal swabs at Visits 2, 3, 4, and 5; and log-transformed viral load (by qPCR and TCID50) area under the curves (AUCs)
• The total dose of acetaminophen (paracetamol) used during the study
• Incidence of physician-diagnosed secondary respiratory tract infections leading to a prescription for antibiotic therapy
• Time to return to normal activity
• Safety: Adverse events (AEs) and clinical laboratory tests for systemic safety including hematology, clinical chemistry, and urinalysis
• Population PK analysis of favipiravir with assessment of maximum plasma concentration (Cmax), minimum plasma concentration (Cmin), and total daily exposure AUC(0-24h) on Visits 1, 2, 3, 4 and 5
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | No |
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) | No |
E.8.2.2 | Placebo | Yes |
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
| No |
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 | 20 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 72 |
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 |
Australia |
Belgium |
Bulgaria |
Hungary |
Netherlands |
New Zealand |
Poland |
Russian Federation |
South Africa |
Spain |
Sweden |
Turkey |
Ukraine |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |