E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of experimental influenza |
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MedDRA Classification |
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 virologic activity of peramivir by intravenous administration compared to placebo against experimental challenge with A/Panama/2007/99. |
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E.2.2 | Secondary objectives of the trial |
To assess the safety and tolerability of peramivir 400 mg administered intravenously once daily for five days to healthy adults aged 18 to 49 years who are selected based on serologic evidence of susceptibility to A/Panama/2007/99.
To assess the frequency and severity of influenza symptoms in subjects receiving either peramivir or placebo following experimental challenge with A/Panama/2007/99.
To assess the time to resolution of fever in subjects receiving either peramivir or placebo following experimental challenge with A/Panama/2007/99.
To assess the pharmacodynamic relationship between exposure to peramivir (as measured by plasma drug concentrations) and virological response. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
A subject will be eligible for enrollment if all of the following apply:
1. Male or Female (non-pregnant, non-lactating), age 18 to 49 years, inclusive. 2. Comprehension of the study requirements; availability for the required study period, ability to attend scheduled study visits, and willingness to participate in the inpatient challenge. 3. Willingness to provide written consent for participation after reading the Consent Form and after having adequate opportunity to discuss the study with an Investigator or qualified deputy. 4. Good general health status as determined by a screening evaluation completed ≤ 42 days prior to challenge. 5. For female subjects, provision of a history of reliable contraceptive practices (hysterectomy or bilateral tubal ligation, oral or implanted contraceptive use, intrauterine device, barrier method plus spermicide, history of a single male partner with vasectomy, or a history of sexual abstinence deemed credible by the Investigator). Males enrolled must ensure that their female partners of childbearing potential utilize approved contraceptive methods to avoid pregnancy. 6. Reciprocal serum titer of serum haemagglutinationinhibiting (HAI) antibody to A/Panama/2007/99 that is ≤ 10. |
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E.4 | Principal exclusion criteria |
Subjects with any of the following will be excluded from possible enrolment in the study: 1. Presence of significant acute or chronic, uncontrolled medical or neuropsychiatric illness (subjects with uncomplicated chronic conditions or diseases that are deemed stable and under satisfactory treatment for ≥ three (3) months (e.g., mild hypertension well-controlled with medication) may be enrolled, provided neither the condition and/or the therapy being received are known to be associated with an immunocompromised state or increased risk of complications of influenza). 2. Venous access deemed inadequate for the administration of intravenous study drug or the phlebotomy requirements of the study. 3. Positive serologic test for HIV infection, or evidence of illicit drug use as determined by urine screening. 4. ALT or AST > 2x the upper limit of normal; serum creatinine > 1.6 mg/dL, or any clinical laboratory test value deemed by the Investigator to indicate or suggest significant undiagnosed acute or chronic illness. 5. Abnormal ECG at the screening visit demonstrating medically significant dysrhythmia and/or suggestive of ischemia or myocardial disease. 6. In female subjects, a positive urine β-HCG during screening, or on the day of influenza virus challenge. 7. During the 4 weeks prior to challenge, daily use for at least 14 days of any oral medication or other product (prescription or over-the-counter), for symptoms of rhinitis or nasal congestion; or chronic use of any intranasal medication for any indication. 8. Any history during adulthood of Asthma or Chronic Obstructive Pulmonary Disease (COPD) of any etiology; and any history of chronic nasopharyngeal disease or complaint (e.g. nasal polyps, chronic rhinitis). 9. Subjects who are habitual smokers. Occasional smokers (defined as ≤ 4 cigarettes/week) who are willing to desist for the duration of the inpatient challenge component of the study may be eligible. 10. Acute use of any medication or other product, prescription or over-the-counter, for symptoms of rhinitis or nasal congestion within seven (7) days prior to the first study drug dose. 11. Any anatomic or neurologic abnormality impairing the pharyngeal gag reflex or condition associated with an increased risk of aspiration, or a history suggestive of such a problem. 12. Receipt of systemic (oral or injectable) glucocorticoids (in a dose ≥ 5 mg prednisone daily or equivalent) within one (1) month of challenge, or receipt of any other cytotoxic or immunosuppressive drug within six (6) months of challenge. 13. Receipt of any investigational drug within one (1) month, or prior participation in any clinical trial evaluating treatment or prevention of influenza virus infection within six (6) months. 14. Presence of any febrile illness or symptoms of upper respiratory infection (greater than grade 1, “mild”) at a time after admission to the CRU and up to the time of planned influenza virus challenge (Such subjects may be re-evaluated for enrollment after resolution of the illness). |
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E.5 End points |
E.5.1 | Primary end point(s) |
The change (reduction) from baseline in influenza virus titer by serial measurements of tissue culture infective dose (TCID50). |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
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.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
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 | Information not present in EudraCT |
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
| |
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 | 3 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 0 |