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 St udy

A Phase 3 Study of CS-8958− A randomized study of CS-8958 comparing two inhalers inpatients with influenza virus infection −Investigators
Study Centre(s)Publication (reference)

Not published.

Studied Period
Phase of Development

Phase 3

Objectives

The objective of this study is to assess and compare theefficacy, safety and pharmacokinetics of a single inhalationof CS-8958 40 mg between an inhaler for commercial use(TwinCaps) and an inhaler for investigational use inpatients with type A or B influenza virus infection.

Methodology

A multicenter, randomized, open-label comparative study

Number of Patients (planned

Planned number of patients : 140 subjects (70 in theand analyzed)

TwinCaps group and 70 in the investigational use group)
The target number of subjects required forpharmacokinetic evaluation was 10 for each group.
Full analysis set (FAS): 182 subjects(90 in the TwinCaps group and 92 in the investigational use group)

Diagnosis and Main Criteria

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

the following criteria: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 consent4)
Test Product, Dose and Mode

Aged ≥ 20 years as of informed consent drug using the inhaler

CS-8958-20TC

of Administration

CS-8958
Subjects received a single inhalation of CS-8958 40 mg using
either TwinCaps or the investigational use inhalers.

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: The TwinCaps and the investigational use groups
were compared using the generalized Wilcoxon test.The mediandifference (the TwinCaps group − the investigational use group)and the 95% CI was calculated based on the generalized Wilcoxon
test statistics.
Safety Analysis;
Adverse Events:
The number of subjects and the incidence by treatment group werecalculated for all adverse events and adverse events consideredrelated to the study drug. They were also summarized by event andseverity. The number of subjects with serious adverse events andadverse events considered related to the study drug and theirincidences were calculated by treatment group.

Summary - Conclusion

Efficacy (primary endpoint):
A Kaplan-Meier plot of the time to alleviation of influenza illness,the primary endpoint, showed that recovery from influenza illness
was similar in the TwinCaps and the investigational use groups.
The median time to alleviation of influenza illness was 72.0 hours
in the TwinCaps group and 78.0 hours in the investigational use
group. The median difference (95% CI) was −6.0 (−23.9 to 6.7)
hours and the time to alleviation of influenza illness wascomparable between the two groups.
Safety:The incidence of adverse events was 20.9% (19/91) in theTwinCaps group and 12.1% (11/91) in the investigational use
group.

Date of ReportAugust 30, 2011