E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Treatment of influenza caused by viruses type A and B |
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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 | 16.1 |
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 | 16.1 |
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.1.3 | 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 efficacy of two doses of inhaled laninamivir octanoate (40 and 80 mg) delivered via TwinCaps® DPI in adults with symptomatic presumptive influenza A or B infection |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the safety and tolerability of laninamivir octanoate
- To evaluate the incidence of secondary bacterial infections and the use of antibiotics
- To evaluate the efficacy of laninamivir octanoate
- To evaluate the quantitative changes in virus shedding
- To investigate the development of resistance to laninamivir by phenotypic and genotypic analyses
- To investigate the impact of treatment of influenza with laninamivir octanoate on quality of life
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Pharmacokinetic sub-study (selected sites only) |
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E.3 | Principal inclusion criteria |
1. Provide written informed consent
2. Males or females aged 18–64 years, inclusive
3. A female subject is eligible to enter the study if she meets following criteria:
- not pregnant or breast feeding / lactating
- females of non-childbearing potential
- females of child bearing potential must have a negative urine pregnancy test at screening
- females of childbearing potential must agree to use adequate and highly effective methods of contraception throughout the study (See Section 4.5).
4. Male subjects with female partners of childbearing potential must use adequate and highly effective methods of contraception such as double-barrier method, from screening until 1 month after their last dose of study drug (See section 4.5).
5. Symptomatic presumptive influenza A or B infection defined as the presence of:
a. a fever of ≥38.0 ºC (≥100.4 ºF) at the screening
AND
b. ≥1 moderate systemic symptom (headache, feeling feverish, body aches and pains, and fatigue)
AND
c. ≥1 moderate respiratory symptom (cough, sore throat and nasal congestion)
6. Onset of illness no more than 40 hours prior to randomization. Onset of illness is defined as the time, the first of any one of the following, occurred:
a. time when the subjects’ temperature was measured as elevated (≥38.0 °C (≥100.4 ºF)
OR
b. time when the subject first experienced at least one respiratory symptom (cough, sore throat and nasal congestion)
OR
c. time when the subject first experienced at least one systemic symptom (headache, feeling feverish, body aches and pains, and fatigue) |
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E.4 | Principal exclusion criteria |
1. Use of antiviral treatment for influenza (e.g. zanamivir, oseltamivir, rimantadine, or amantadine) within 14 days prior to screening
2. Received live attenuated or trivalent inactivated influenza virus vaccine in the previous 3 weeks
3. History or presence of clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, cystic fibrosis, or bronchiectasis) or asthma
4. History of congestive heart failure with symptoms consistent with New York Heart Association Class III or IV functional status (See Appendix A: ) within the past 12 months
5. Presence of an immune compromised status due to chronic illness, organ transplantation or use of daily systemic immunosuppressants within 30 days prior to screening
6. Presence of clinically significant signs of acute respiratory distress during screening
7. Current use of inhaled medications (nasal or oral) or anticipated use of inhaled medications (nasal or oral) at any time during the study
8. Current or a history of acute or chronic renal impairment requiring hemodialysis and/or a known calculated creatinine clearance (CLCR) of <60 mL/min
9. Presence of clinically significant abnormalities on ECG at screening which, in the investigator's clinical judgment, may affect either the subject’s ability to participate in the study or the study results
10. History or presence of any clinical condition or evidence of organ dysfunction on examination which, in the opinion of the investigator, may affect either the subject’s ability to participate in the study or the study results
11. Currently hospitalized or any planned hospitalizations within 1 month following the last dose of study drug
12. Current clinical evidence of otitis, bronchitis, sinusitis, pneumonia or active bacterial infection at any body site, that requires treatment with oral or parenteral antibiotics
13. Documented or reported (known) history of hepatitis B, hepatitis C, TB or HIV infection
14. Severe infection within 30 days prior to screening which required parenteral antibiotic use or hospitalization
15. History of or known clinically significant liver disease
16. History of, or current evidence of, abuse (in the investigator’s opinion) of alcohol or any licit or illicit drug substance within the past 12 months
17. History of adverse reaction or known hypersensitivity to lactose or neuraminidase inhibitors
18. Received an investigational drug within 30 days prior to screening
19. Subjects who in the opinion of the investigator are unable to independently complete study documentation e.g. Flu-iiQ™ or self-administer laninamivir octanoate TwinCaps® DPI |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary end point for this study is time to alleviation of influenza symptoms (cough, sore throat, nasal congestion, headache, feeling feverish, body aches and pains and fatigue) and fever for ≥24 hours. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The time of symptom alleviation is defined as the period from start of study drug to the start of the first 24 hour period (three consecutive measurements) in which the influenza symptoms are scored as mild or absent and fever is absent (<38.0 °C / <100.4 ºF). |
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E.5.2 | Secondary end point(s) |
- Time to return to body temperature of <37.2 °C /99.0 ºF
- Time to alleviation of systemic symptoms
- Time to alleviation of respiratory symptoms
- Flu-iiQ symptom domain scores; systemic symptoms, respiratory symptoms and all flu symptoms
- Area under the curve (AUC) of the duration and severity of the mean all symptom score
- Determination of dose-response relationship in influenza infected subjects
- Determination of the incidence of secondary bacterial infections and the use antibiotics
- Incidence of SAEs, AEs leading treatment discontinuation, clinically significant changes in haematology, biochemistry and urinalysis laboratory tests
- Use of concomitant medications
- Changes on clinical assessments; vital signs, ECGs, physical examinations and spirometry
- Quantitative changes in virus shedding based on qRT-PCR and viral culture
- Determination of the emergence of resistance to laninamivir by phenotypic and genotypic analyses
- Quality of Life; impact on daily activities, impact on emotions and impact on others |
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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 | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 74 |
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 |
Belgium |
Bulgaria |
Canada |
France |
New Zealand |
Australia |
Colombia |
Estonia |
Germany |
Hungary |
Latvia |
Mexico |
Peru |
South Africa |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |