E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of Influenza [seasonal or pandemic (H1N1) 2009] |
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E.1.1.1 | Medical condition in easily understood language |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10022001 |
E.1.2 | Term | Influenza (epidemic) |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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 | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10022000 |
E.1.2 | Term | Influenza |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
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 | 10021881 - Infections and infestations |
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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 safety of oseltamivir administered by intravenous infusion in the treatment of influenza [seasonal or pandemic (H1N1) 2009 influenza] |
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E.2.2 | Secondary objectives of the trial |
• To evaluate the pharmacokinetics of oseltamivir and oseltamivir carboxylate following IV administration of oseltamivir in patients with influenza
• To evaluate viral load and shedding
• To evaluate all isolates for phenotypic and, where necessary, genotypic resistance |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male and female adults and adolescents, 13 years of age and older, except in Germany and Denmark, where the subjects enrolled should be 18 years of age or older.
• In France, patients enrolled into the renal impairment arm must be 18 years of age or older.
• Diagnosis of influenza (in Spain, Denmark and Germany: severe influenza requiring hospitalization) by virology testing or clinical diagnosis based on symptoms suggestive of influenza
• In Spain, Denmark and Germany: Hospitalized patients or requiring hospitalization and/or who are medically evaluated to not be good candidates for oral treatment and/or who might benefit from the IV administration of oseltamivir.
• Less than or equal to 144 hours between the onset of influenza-like illness and first dose of study medication
• Patient is willing and able to comply with study requirements and give consent, or, if applicable, consent may be given by a parent, legal guardian or legal representative
• Except in Spain, Denmark, and Germany: Patients who are pregnant may be enrolled only if the potential benefit justifies the potential risk to the fetus
• Except in Spain and Denmark: Patients who are lactating may be enrolled only if the potential benefit for the lactating mother justifies the potential risk to the breast-fed infant. In Germany, patients who are
lactating must also be unable to receive oral oseltamivir.
• In Spain and Denmark: Subjects who are in the reproductive age group and sexually active must agree to utilize and an effective method of contraception throughout the study period and for one reproductive cycle following cessation of the study therapy. |
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E.4 | Principal exclusion criteria |
• Patients with clinical evidence of severe hepatic decompensation at the time of randomization (e.g., evidence of jaundice, ascites, hepatic encephalopathy, and coagulation disturbances-Child-Pugh score above 9).
• Electrocardiogram showing acute ischemia or significant arrhythmia
• Allergy to test medication
• Patients taking probenicid medication within 7 days before starting study medication
• Participation in a clinical trial or expanded access trial with an investigational drug in the 4 weeks prior to randomization (for renally impaired patients: 4 weeks prior to first dose of study medication).
• In Germany: Pregnant women
• In Spain and Denmark: Pregnant and lactating women |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoints for safety will be assessments of adverse events, laboratory tests, vital signs and ECG measurements |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Adverse Events are evaluated throughout the study. Vital signs are
evaluated at study visits Day 1, 6, 11, 15, 30 as well as at each IV dose.
Laboratory tests are on Day 1, Day 3 or 4, within 24 hours of last IV dose
and at Day 30. ECGs are before and after the 1st and 5th or 6th infusion
as well as at Day 30. |
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E.5.2 | Secondary end point(s) |
1) Occurrence or non-occurrence of shedding virus by culture
2) Occurrence or non-occurrence of shedding virus by RT-PCR
3) Viral load by culture
4) Body temperature
5) Absence or presence of fever, where fever is defined as a body
temperature ≥ 37.8°C
6) Absence or presence of symptoms of influenza—for example, nasal
congestion, sore throat, cough, aches and pains, fatigue, headache or
chills/sweats (feverish), vomiting, diarrhea |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) On Days 1, 4, 6, 11, 15 and 30
2) On Days 1, 4, 6, 11, 15 and 30
3) On Days 1, 4, 6, 11, 15, and 30
4) Twice daily
5) Twice daily
6) On Days 1, 11, 15 and 30
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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) | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
100mg group compared with 200mg group |
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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 | Information not present in EudraCT |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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 |
Denmark |
France |
Germany |
Hungary |
Italy |
Lithuania |
Poland |
Romania |
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 NV25118 is defined as the last observation of all patients enrolled. These observations include safety laboratory and virology laboratory results. |
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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 | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 0 |