Safety & Pharmacokinetics Study of Inhaled Laninamivir Octanoate TwinCaps® Dry Powder Inhaler in Children With Influenza

Study Overview
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Brief Summary
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This Phase 1/2 protocol is designed to collect safety, tolerability and pharmacokinetic data of two doses of Laninamivir Octanoate in children and adolescents. The protocol will also explore virology and efficacy endpoints.

Detailed Description
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Approximately 48 subjects aged 5-17 years inclusive will be randomised into the study. Subjects with recent onset of presumptive influenza will have influenza A or B infection confirm by Rapid Antigen Test. The study will be conducted on an outpatient basis. The dose is administered in a single session in the clinic on Day 1. The subject will return to the clinic for assessments and follow up.

Official Title
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Randomised, Parallel Dose, Phase 1/2 Safety and Pharmacokinetics Study of Inhaled Laninamivir Octanoate TwinCaps® Dry Powder Inhaler in Children With Naturally Acquired Influenza A or B

Conditions
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Influenza

Intervention / Treatment
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* Drug: 20 mg laninamivir octanoate
* Drug: Placebo
* Drug: 40 mg laninamivir octanoate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects' parent/legally acceptable representative/guardian must give written informed consent to participate in the study and must understand the nature of the study and must be willing to comply with all protocol requirements. Subjects over 12 must provide assent to participate in the study and potential subjects below this age should provide assent if deemed appropriate to the maturity level of the subject or if required according to local guidance/regulations. Males or females aged between 5 and 17 years inclusive, who weigh at least 15 kg at screening. Confirmed influenza infection based on positive rapid antigen test (RAT) for Influenza A or B. Fever, defined as either: Otic temperature ≥38.0° C (100.4°F) 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. Presence on the Screening questionnaire of, at least two, of the following influenza symptoms: Non-productive Cough, of at least moderate severity, Sore throat, of at least moderate severity, Nasal congestion/runny nose, of at least moderate severity, Headache, of at least moderate severity, Muscle aches and pain, of at least moderate severity, Feeling feverish, of at least moderate severity, Low energy, tired, fatigue, of at least moderate severity; Onset of illness no more than 40 hours before randomization, defined as: time when the temperature was first measured as elevated ≥38.0°C (oral or otic) OR time when the subject first experienced at least one influenza symptom (non-productive cough, sore throat or nasal congestion/runny nose, headache, muscle aches and pain, feeling feverish, or low energy/tired/fatigue) In the Investigator's opinion able to complete the required inhalations of the investigational medicinal product. Exclusion Criteria: Use of antiviral treatment for influenza (e.g., zanamivir, oseltamivir, peramivir, rimantadine, or amantadine) within 14 days prior to screening Received influenza virus vaccine in the previous 3 weeks. History or presence of clinically significant pulmonary disease (e.g., chronic obstructive pulmonary disease, cystic fibrosis, or bronchiectasis) Current asthma requiring treatment, or history of asthma requiring treatment in the last 5 years, or episode of wheezing in the 12 months prior to randomization. History of congestive heart failure with symptoms consistent with New York Heart Association Class III or IV functional status. Presence of an immune compromised status due to chronic illness, organ transplantation or use of daily systemic immunosuppressants Presence of clinically significant signs of acute respiratory distress during screening. Current use of inhaled medications (nasal or oral) or anticipated use of inhaled medications (nasal or oral) at any time during the study. Current or a history of acute or chronic renal impairment/disease Currently hospitalized or any planned hospitalizations within 1 month following the last dose of IMP. Current clinical evidence of otitis, bronchitis, sinusitis, or pneumonia or active bacterial infection at any body site Severe infection within 30 days prior to screening which required parenteral antibiotic use or hospitalization.

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 20mg Laninamivir Octanoate<br>Dry Powder plus placebo | Drug: 20 mg laninamivir octanoate<br> <br> * Other names: CS-8958;Drug: Placebo<br> <br> * Other names: Lactose;|
| Experimental: 40mg Laninamivir Octanoate<br>Dry Powder | Drug: 40 mg laninamivir octanoate<br> <br> * Other names: CS-8958;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the safety and tolerability of laninamivir octanoate following administration of the dose by inhalation in children with influenza A or B infection | Safety data will be presented according to dose group and age strata. All safety data will be summarized with descriptive statistics, and include assessment of SAEs, AEs, Clinically Significant changes in routine labs, O2 Saturation, ECG, Vitals, Con Meds, Physical Exam findings. | Subjects are assessed at clinic visits and followed up to 28-days post dose. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the pharmacokinetic (PK) profiles of the prodrug, laninamivir octanoate, and its active metabolite, laninamivir, following administration of a single dose (20 or 40 mg) | Pharmacokinetic parameters will be calculated and summarized, PK concentration data will add to population models. | Samples are collected at clinic visits over 5 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza treatment, pediatric, laninamivir