E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Respiratory Viral Infections due to influenza A or B virus, RSV, adenovirus, or parainfluenza virus 1 or 3 |
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E.1.1.1 | Medical condition in easily understood language |
Infections due to influenza |
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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 | 17.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10022005 |
E.1.2 | Term | Influenza viral infections |
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 evaluate the clinical efficacy of Isoprinosine compared with placebo in subjects with laboratory confirmed acute respiratory viral infections due to influenza A or B virus, RSV, adenovirus, or parainfluenza virus 1 or 3. |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the clinical efficacy of Isoprinosine compared with placebo in subjects with clinically diagnosed influenza-like illnesses.
• To evaluate the effect of Isoprinosine compared with placebo:
- on ability to perform activities of daily living in subjects with laboratory confirmed acute respiratory viral infections due to influenza A or B virus, RSV, adenovirus, or parainfluenza virus 1 or 3.
- on the ability to perform activities of daily living in subjects with clinically diagnosed influenza-like illnesses.
- on the incidence of complications of influenza-like illness and laboratory confirmed acute respiratory viral infections due to influenza A or B virus, RSV, adenovirus, or parainfluenza virus 1 or 3.
• To assess the safety of Isoprinosine compared with placebo in the treatment of influenza-like illnesses. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or nonpregnant female subjects aged 18 to 55 years.
Female subjects must be either surgically sterile, postmenopausal (no menses during the previous 12 months), or must be practicing an effective method of birth control as determined by the investigator (eg, oral contraceptives, double barrier methods, injectable or implanted hormonal contraceptives, tubal ligation, or male partner with vasectomy or complete abstinence).
2. Has an influenza-like illness defined as:
• oral temperature of ≥38°C obtained at study site. If oral temperature measured at screening is <38°C, then the subject will still be eligible if he or she has self-measured the oral temperature at home as ≥38°C within 12 hours prior to screening and have taken an antipyretic within 4 hours prior to screening
• at least 1 of the following respiratory symptoms: cough, sore throat, or nasal obstruction that is considered by the subject to be moderate or severe in intensity (rated greater than “mild” on a 4-point scale , and
• at least 1 of the following constitutional symptoms: fatigue, headache, myalgia, or feverishness that is considered by the subject to be moderate or severe in intensity (rated greater than “mild” on a 4-point scale ).
3. Has onset of influenza-like illness no more than 36 hours prior to screening, defined as when the subject experienced fever and at least 1 respiratory symptom and at least 1 constitutional symptom.
4. Is capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements, including completion of the subject diary.
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E.4 | Principal exclusion criteria |
1. Has immunosuppressive disorder or who is receiving immunosuppressive therapy (eg, immunosuppressants, antitumour agents).
2. Is receiving treatment with xanthine oxidase inhibitors (allopurinol) or uricosuric agents, or treatment with thiazide diuretics (eg, hydrochlorothiazide, chlorthalidone, and indapamide) or loop diuretics (eg, furosemide, torsemide, and ethacrynic acid).
3. Has chronic renal dysfunction (creatinine clearance <50 mL/min).
4. Has liver disorder (severe liver function impairment; aspartate aminotransferase and alanine aminotransferase values greater than 3 times the upper limit of normal).
5. Is lactose intolerant.
6. Has cancer in a nonremission stage (subject with nonmetastatic basal cell or squamous cell skin cancer or other early cancer for which surgical resection is considered to be completely curative is eligible for enrolment).
7. Is a resident of a nursing home or other long-term care institution.
8. Is receiving treatment with zidovudine.
9. Is pregnant or lactating/breastfeeding female.
10. Has received any dose of Isoprinosine, oseltamivir, zanamivir, amantadine, or rimantadine during this period of influenza-like illness.
11. Has received prior treatment with any investigational drug or vaccine within 30 days prior to screening.
12. Has known hypersensitivity to inosine acedoben dimepranol or any of the excipients comprising Isoprinosine from the 500 mg Isoprinosine tablets.
13. Has a medical history of hyperuricaemia or gout.
14. Is unable to take oral medications.
15. Has any preexisting illness that, in the opinion of the investigator, would place the subject at an increased risk through participation in this study.
16. Is a subject who, in the judgment of the investigator, will be unlikely to comply with the requirements of this protocol.
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to resolution of all influenza-like symptoms present at baseline to none (ie, score of 0 on influenza-like symptoms assessment scale) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Subjects will be instructed to record the presence of influenza like illness respiratory and constitutional symptoms once daily in the evening using the 4 point scale on subject diary cards. |
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E.5.2 | Secondary end point(s) |
• Time to resolution of all constitutional symptoms present at baseline to none (ie, score of 0 on influenza-like symptoms assessment scale)
• Time to resolution of cough present at baseline to none (ie, score of 0 on influenza-like symptoms assessment scale)
• Time to resolution of sore throat present at baseline to none (ie, score of 0 on influenza-like symptoms assessment scale)
• Time to resolution of nasal obstruction present at baseline to none (ie, score of 0 on influenza-like symptoms assessment scale)
• Time to absence of fever (oral temperature of ≤37.5°C for at least 2 consecutive readings at least 12 hours apart)
• Time to resumption of normal activity (ie, score of 0 on daily activities assessment scale)
• Frequency of viral respiratory infection complications of hospitalisation, death due to influenza-like illness or complications of influenza-like illness, and requirement for antibiotics to treat secondary bacterial infections
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Subjects will be instructed to measure oral temperature using a digital thermometer 3 times daily and record these readings in the subject diary cards starting from Day 1 after the first dose of study drug until the EOT Visit. |
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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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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) | 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 | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 25 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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Last Patient Last Visit (LPLV) |
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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 | |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 9 |