Efficacy and Safety Study of Laninamivir Octanoate TwinCaps® Dry Powder Inhaler in Adults With Influenza

This Phase 2 protocol is designed to compare two dose levels of laninamivir octanoate versus placebo. The objectives are to obtain safety and efficacy in adults aged 18 to 64 years who present to clinic with symptomatic presumptive influenza A or B infection.

Approximately 636 subjects will be randomized into the Study.

Following confirmation of circulating influenza in the local area, eligible subjects with recent onset of symptomatic presumptive influenza A or B infection will be enrolled in the study. Subjects must be randomized within 40 hours of the first symptom onset. Subjects will be randomized to placebo, 40 or 80 mg of laninamivir octanoate.

The study will be conducted on an outpatient basis. The first dose of study drug will be administered via inhalation within 4 hours of randomization in the clinic, followed by a second dose at home. Participants will be followed for 14 days to assess efficacy, virology and safety. Outpatient visits to the investigational site are scheduled on Days 2 (optional PK Sub-study Visit) 3, 5, 8, 15. An End of study visit will be performed on Day 29.

Eligibility Criteria:
Main Inclusion Criteria:

1. Provide written informed consent
2. Males or females aged 18-64 years, inclusive
3. Symptomatic presumptive influenza A or B infection defined as the presence of:

   1. a fever of ≥38.0ºC (≥100.4 ºF) at the screening visit OR a history of fever within the 24 hours prior to the screening visit and has administered antipyretic(s) in the 6 hours prior to the screening visit AND
   2. ≥1 moderate systemic symptom (headache, feeling feverish, body aches and pains, and fatigue) AND
   3. ≥1 moderate respiratory symptom (cough, sore throat and nasal congestion)
4. 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:

   1. time when the subjects' temperature was measured as elevated (≥38.0°C (≥100.4ºF) OR
   2. time when the subject first experienced at least one respiratory symptom (cough, sore throat and nasal congestion) OR
   3. time when the subject first experienced at least one systemic symptom (headache, feeling feverish, body aches and pains, and fatigue)

Main 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
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 or calculated creatinine clearance (CLCR) of \<60 mL/min
9. 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