SYNOPSIS
Name of Sponsor/Company

Daiichi Sankyo Co., Ltd.

Name of Finished Product

INAVIRⓇ DRY POWDER INHALER 20mg

Name of Active IngredientLaninamivir Octanoate Hydrate（JAN）

Title of Study

A Phase 3 Study of CS-8958− A randomized double-blind comparative study of CS-8958 inpatients with influenza virus infection aged 10 to 19 years −Investigators
Study Centre(s)Publication (reference)

Not published.

Studied Period
Phase of Development

Phase 3Objectives

A randomized, double-blind comparative study wasconducted to assess the efficacy and safety after a single
inhalation of CS-8958 20 mg or 40 mg in patients (aged 10to 19 years) with type A or B influenza virus infection.

Methodology

A2-arm,multicenter,randomized,uncontrolled,double-blind, parallel comparative study
Number of Patients (planned

Planned number of patients : 120 subjects

and analyzed)(CS-8958 20 mg group: 60 subjects, CS-8958 40 mg group:60 subjects)
Full analysis set (FAS): 120 subjects(CS-8958 20 mg group: 64 subjects, CS-8958 40 mg group: 56subjects)

Diagnosis and Main Criteria

Patients with type A or B influenza virus infection who met all offor Inclusion

the following inclusion criteria were enrolled in this study.
1)

Influenza virus-positive by an influenza rapid diagnostic kit,
and diagnosed with influenza virus infection by theinvestigators

2)

Body temperature (axillary) ≥ 37.5°C at the time of informed
consent

3)

Within 36 hours after the onset of any influenza symptoms(fever [feeling of fever], headache, myalgia/arthralgia,
fatigue, chill/sweating, nasal symptoms, sore throat, cough) at
the time of informed consent

4)Aged 10 to 19 years as of informed consent5)

Patients the investigators considered able to inhale the studydrug using the inhaler
Test Product, Dose and ModeCS-8958

of Administration

CS-8958 placebo
Subjects received a single inhalation of CS-8958 20 or 40 mg using
an inhaler.

Duration of Treatment

Single dose

Reference Therapy, Dose andNone

Mode of Administration
Criteria for Evaluation

Primary Endpoint: Time to Alleviation of Influenza Illness

Statistical Method

Efficacy Analysis;Primary analysis: Kaplan-Meier plots were prepared, summary
statistics including the median time to alleviation of influenza
illness and 95% confidence intervals (CIs) were calculated bygroup, and a generalized Wilcoxon test was performed between
CS-8958 doses. The inter-dose difference in the median (40 mggroup − 20 mg group) was calculated and its 95% CI was
calculated based on the statistics obtained by the generalized
Wilcoxon test.
Safety Analysis;
1) Adverse Events
The number of subjects with adverse events and their incidence
were presented by causal relationship (all/related) by treatmentgroup. Serious adverse events, severe adverse events anddiscontinuations due to adverse events were also calculated. The
number of subjects with each adverse event and the incidence werepresented for causal relationship (all/related) and for severity andcausal relationship (all/related) by treatment group.
2) Clinically Significant Adverse Events
The number of subjects with neuropsychiatric events during
influenza infection (all, by category) was calculated by treatmentgroup.

Summary - Conclusion

Efficacy (primary endpoint):
The median time to alleviation of influenza illness, which was theprimary endpoint, was 87.1 hours in the 20 mg group and 76.0
hours in the 40 mg group. The median difference (95% CI)
between the 20 mg group and 40 mg group was −11.1 (−32.9 to13.0) hours and the time to alleviation of influenza illness wasshorter in the 40 mg group compared to the 20 mg group, though it
was not statistically significant. The hazard ratio (95% CI) of the40 mg group to 20 mg group was 1.127 (0.782 to 1.624) and no
significant difference was noted.
Safety:The incidence of adverse events was 28.1% (18/64) in the 20 mggroup, 28.6% (16/56) in the 40 mg group and 28.3% (34/120) in
the overall population, and comparable between the 20 mg and 40mg groups. The incidence of neuropsychiatric events was 3.1%(2/64) in the 20 mg group, 7.1% (4/56) in the 40 mg group and5.0% (6/120) in the overall population.
Date of ReportAugust 30, 2011