Influenza
Conditions
Keywords
Influenza Laninamivir Octanoate
Brief summary
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.
Detailed description
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.
Interventions
Sponsors
Department of Health and Human Services
Biota Scientific Management Pty Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 64 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Alleviation of Influenza Symptoms | Efficacy will be assessed over 14 days post-randomization. | Time to alleviation of influenza will be assessed through Flu-iiQ (Influenza intensity and impact Questionnaire) and diary cards from Day 1 to 14. |
Countries
Australia, Belgium, Bulgaria, Canada, Colombia, Estonia, France, Germany, Hungary, Latvia, Mexico, New Zealand, Peru, South Africa, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 40 mg Laninamivir Octanoate DPI 40 mg Laninamivir Octanoate and matching placebo
40 mg Laninamivir Octanoate
Placebo | 213 |
| 80 mg Laninamivir Octanoate DPI 80 mg Laninamivir
80 mg Laninamivir Octanoate | 214 |
| Placebo Matching Placebo
Placebo | 212 |
| Total | 639 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Dosing error | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 5 | 1 | 3 |
| Overall Study | Met exclusion criteria | 1 | 0 | 0 |
| Overall Study | Randomized in error | 1 | 0 | 0 |
| Overall Study | Respiratory distress during spirometry | 0 | 0 | 1 |
| Overall Study | Subject noncompliance | 0 | 1 | 1 |
| Overall Study | Unable to complete measurements | 1 | 0 | 0 |
| Overall Study | Unable to complete spriometry | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 7 | 3 |
Baseline characteristics
| Characteristic | 40 mg Laninamivir Octanoate DPI | 80 mg Laninamivir Octanoate DPI | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 38.5 years STANDARD_DEVIATION 11.95 | 39.2 years STANDARD_DEVIATION 12.49 | 40.3 years STANDARD_DEVIATION 13.31 | 39.3 years STANDARD_DEVIATION 12.6 |
| Region of Enrollment Belgium | 13 participants | 8 participants | 14 participants | 35 participants |
| Region of Enrollment Bulgaria | 27 participants | 32 participants | 36 participants | 95 participants |
| Region of Enrollment Canada | 2 participants | 2 participants | 3 participants | 7 participants |
| Region of Enrollment Estonia | 11 participants | 13 participants | 15 participants | 39 participants |
| Region of Enrollment Germany | 6 participants | 4 participants | 3 participants | 13 participants |
| Region of Enrollment Hungary | 1 participants | 1 participants | 1 participants | 3 participants |
| Region of Enrollment Latvia | 1 participants | 3 participants | 4 participants | 8 participants |
| Region of Enrollment Mexico | 7 participants | 12 participants | 10 participants | 29 participants |
| Region of Enrollment New Zealand | 2 participants | 4 participants | 3 participants | 9 participants |
| Region of Enrollment South Africa | 40 participants | 38 participants | 39 participants | 117 participants |
| Region of Enrollment United Kingdom | 1 participants | 0 participants | 0 participants | 1 participants |
| Region of Enrollment United States | 102 participants | 97 participants | 84 participants | 283 participants |
| Sex: Female, Male Female | 119 Participants | 128 Participants | 115 Participants | 362 Participants |
| Sex: Female, Male Male | 94 Participants | 86 Participants | 97 Participants | 277 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 213 | 0 / 214 | 0 / 212 |
| other Total, other adverse events | 31 / 212 | 27 / 211 | 21 / 211 |
| serious Total, serious adverse events | 1 / 212 | 1 / 211 | 1 / 211 |
Outcome results
Primary
Time to Alleviation of Influenza Symptoms
Time to alleviation of influenza will be assessed through Flu-iiQ (Influenza intensity and impact Questionnaire) and diary cards from Day 1 to 14.
Time frame: Efficacy will be assessed over 14 days post-randomization.
Population: Intent-to-treat-infected (ITT-I) population - all ITT subjects with laboratory confirmed influenza A or B infection by at least one virological method (qRT-PCR or qCulture) on either Day 1 or 3
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 40 mg Laninamivir Octanoate DPI | Time to Alleviation of Influenza Symptoms | 102.30 hours |
| 80 mg Laninamivir Octanoate DPI | Time to Alleviation of Influenza Symptoms | 103.20 hours |
| Placebo | Time to Alleviation of Influenza Symptoms | 104.10 hours |
p-value: 0.251Log Rank
p-value: 0.818Log Rank