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 4 Study of CS-8958− A randomized double-blind controlled study of laninamivir
comparing with oseltamivir for the treatment of influenza inpatients with chronic respiratory diseases −Investigators
Study Centre(s)Publication (reference)

J Infect Chemother. (Accepted: 17 July 2012, Published
online: 21 August 2012)

Studied Period
Phase of Development

Phase IV

Objectives

The objective of this study is to evaluate the safety andefficacyofCS-8958

inhaledoncecomparing

withoseltamivir in patients with type A or type B influenza
virus

infectioncomplicatedbychronic

respiratory

diseases.
Methodology

Multi-center, randomized, 2-parallel-group, double-blind,
active-controlled study

Number of Patients (planned

Planned number of subjects: 200 subjectsand analyzed)(100 subjects in the CS-8958 group, 100 subjects in theoseltamivir group)
Full analysis set (FAS): 201 subjects(101 subjects in the CS-8958 group, 100 subjects in the oseltamivirgroup)Diagnosis and Main Criteria

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

the following inclusion criteria were eligible to participate in thestudy.
1)

Patients 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)

Patients diagnosed with chronic respiratory diseases (e.g.,bronchial asthma and chronic obstructive pulmonary disease).

5)

Aged ≥ 20 years as of informed consent

Test Product, Dose and ModeCS-8958

of Administration

CS-8958 placebo
Subjects inhaled a single dose of CS-8958 or CS-8958 placebo as asingle inhalation on Day1.

Duration of Treatment

1) CS-8958 group: Single dose (5 days for the control drug)2) Oseltamivir group: 5 days

Reference Therapy, Dose andOseltamivir phosphate 75 mg capsule

Mode of Administration

Oseltamivir phosphate placebo capsuleSubjects in the oseltamivir phosphate group received 75 mg (asoseltamivir) orally twice daily for 5 days.

Criteria for Evaluation

Primary Endpoint: Time to Alleviation of Influenza Illness

Statistical Method

Efficacy Analysis;Primary analysis: The difference in the median time to alleviationof influenza illness between the CS-8958 group and the oseltamivirgroup (CS-8958 group − oseltamivir group) was calculated, andthe 95% confidence interval (CI) was then calculated based on thegeneralized Wilcoxon test statistics. A generalized Wilcoxon test
was performed with the oseltamivir group as the comparator.
Safety Analysis;
Adverse Events: The number of subjects with adverse events andthe incidence of adverse events were presented by causal
relationship (all/drug-related) for each treatment group. Serious
adverse events, severe adverse events, and adverse events leading
to discontinuation were summarized in the same manner. The
number of subjects with individual adverse events and theincidence of individual adverse events were also presented bycausal relationship (all/drug-related) as well as by severity andcausal relationship (all/drug-related) for each treatment group.

Summary - Conclusion

The median time to illness alleviation was 64.7 h in the laninamivirgroup and 59.7 h in the oseltamivir group no significant difference
was found between the treatment groups. The incidence of
influenza-associated complications (pneumonia, bronchitis, otitis
media, and sinusitis) was 5.9% (6/101) in the laninamivir groupand 7.0% (7/100) in the oseltamivir group. The rate of exacerbationof the underlying disease was 7.9% (8/101) in the laninamivirgroup and 7.0% (7/100) in the oseltamivir group. Laninamivir
octanoate showed similar efficacy and safety to oseltamivir in thetreatment of influenza in patients with chronic respiratory diseases.
Date of Report

September 5, 2012