SYNOPSIS
Name of Sponsor/CompanyDaiichi Sankyo Co., Ltd.

Name of Finished Productto be determined

Name of Active Ingredient

Levofloxacin hydrate (JAN)

Title of Study

A phase III, randomized, parallel-group, confirmatory study ofDR-3355 injection in patients with community-acquired pneumonia

Study Centre(s)87 Study Sites

Publication (reference)

None

Studied Period

Date of obtaining first consent: November 22, 2007
Date of last observation: October 1, 2008

Phase of Development

Phase III

Objectives

To confirm the non-inferiority of the efficacy of DR-3355 injection inpatients with community-acquired pneumonia using ceftriaxone
sodium hydrate (ceftriaxone sodium, i.e., ceftriaxone) as a control.
The safety of DR-3355 injection will also be evaluated.

Methodology

Multicenter, randomized (central registration), open-label (primary
efficacy endpoint to be evaluated by a third party (hereinafterreferred to as end-point assessment committee) under blindedcondition), non-inferiority confirmatory study.

Number of Patients (plannedPlanned subjects: 240and analyzed)(DR-3355inj group: 120, ceftriaxone group: 120)
Registered subjects and Randomized subjects: 260(DR-3355inj group: 136, ceftriaxone group: 124)
Analyzed subjects:
Safety analysis set:259(DR-3355inj group: 136, ceftriaxone group: 123)
Per protocol set (PPS): 200(DR-3355inj group: 108, ceftriaxone group: 92)

Diagnosis and Main Criteria

Subjects with community-acquired pneumonia (bacterialfor Inclusion

pneumonia) who met all of the inclusion criteria, did not fulfill anyof the exclusion criteria, and gave written consent (signed) of theirown free will were enrolled in the study.
(1)Men and women aged 20-79 years at the time of giving informedconsent.
(2)Patients who developed symptoms diagnosed as bacterial
pneumonia outside of the hospital and for whom inpatient
treatment was judged necessary by the investigator orsubinvestigator.
(3)Patients who met the following symptoms/findings criteria on theday of or the day before the start of study drug treatment:1)Presence of acute and new infiltrative shadow identified by chest
X-ray or chest CT scanning2)Body temperature ≥37.0°C (axillary)3)Patients who met at least one of the two following:i)CRP increased (≥1.0 mg/dL)ii)White blood cell count increased (≥9,000/mm3)4)Presence of respiratory symptoms such as cough, sputum(purulent sputum), chest pain, and dyspnea, or moist rales.

Test Product, Dose and Mode

Investigational product (lot No.):DR-3355 inj (060551)

of Administration, Batch

Dosage and administration:Intravenous drip infusion of DR-3355 at

Numbera dose of 500 mg once daily over 60 minutes.

Duration of Treatment

Intravenous drip infusion of DR-3355 500 mg once daily orceftriaxone 1 g (potency) twice daily for 7 to 14 days.

Reference Therapy, Dose andComparator (lot No.):Ceftriaxone (Ad3355X0-07T01,ModeAd3355X0-07T02)

ofAdministration,Batch Number

Dosage and administration:Intravenous drip infusion of ceftriaxone
at a dose of 1 g (potency) twice daily (morning and evening) over 30
minutes after dissolving in the attached solution.

Criteria for Evaluation【Efficacy endpoints】
Primary endpoint
Clinical response at completion/discontinuation of treatment
evaluated by the end-point assessment committee (success rate)
Secondary endpoints(1)Clinical response at completion/discontinuation of treatment
evaluated by the investigator or subinvestigator (success rate)(2)Clinical response on Days 3 and 7 and at the last observation
evaluated by the end-point assessment committee (success rate)(3)Microbiologic response at completion/discontinuation oftreatment evaluated by the end-point assessment committee(negative conversion rate)(4)Microbiologic response at completion/discontinuation oftreatment evaluated by the end-point assessment committee(eradication rate)【Safety endpoints】

(1)Incidence of adverse events and of adverse drug reactions(2)Incidence of adverse events and of adverse drug reactions by major
background factors(3)Changes in clinical laboratory values

Statistical Method【Efficacy analysis】
As the primary endpoint, point estimation was obtained for thedifference in clinical response (success rate) atcompletion/discontinuation of treatment evaluated by the end-point
assessment committee between the DR-3355inj group and theceftriaxone group to calculate the two-sided 95% confidence interval
based on the normal approximation. When the lower limit of thetwo-sided 95% confidence interval was ≥-10%, it was judged thatnon-inferiority of the DR-3355inj group to the ceftriaxone group wasconfirmed.
As secondary endpoints, point estimation and the two-sided 95%
confidence interval were calculated for both groups.
【Safety analysis】
The number, the percentage, two-sided 95% confidence interval ofsubjects with adverse events and adverse drug reactions, and thenumber of events in each group were shown for the safety analysis
set. Tabulation was also conducted for the safety data by systemorgan class/preferred terms.

Summary - Conclusion【Results of efficacy】
Primary endpoint: Clinical response at completion/discontinuationof treatment evaluated by the end-point assessment committee(success rate)
The success rate at completion/discontinuation of treatment was
88.5% (92/104) in the DR-3355inj group and 88.8% (79/89) in theceftriaxone group. Because the lower limit of the 95% confidence
interval of the intergroup difference exceeded -10%, non-inferiorityof DR-3355 to ceftriaxone was confirmed.
Secondary endpoints（1）Clinical response at completion/discontinuation of treatmentevaluated by the investigator or subinvestigator (success rate)
The success rate at completion/discontinuation of treatment was
93.5% (101/108) in the DR-3355inj group and 91.2% (83/91) in theceftriaxone group.

（2）Clinical response on Days 3 and 7 and at the last observation(success rate)
The success rate on Days 3, 7 and at the last observation evaluatedby the end-point assessment committee was 45.2% (47/104), 68.0%(34/50), 88.9% (80/90) in the DR-3355inj group and 33.7% (30/89),
78.0% (32/41), 83.8% (62/74) in the ceftriaxone group, respectively.
（3）Microbiologic response at completion/discontinuation oftreatment (negative conversion rate)
Microbiologic response at completion/discontinuation of treatment
evaluated by the end-point assessment committee (negativeconversion rate) was 96.7% (59/61) in the DR-3355inj group and
97.8% (44/45) in the ceftriaxone group.
（4）Microbiologic response at completion/discontinuation of treatment(eradication rate)
Microbiologic response of the pathogen evaluated by the end-point
assessment committee (eradication rate) was 97.2% (69/71) in theDR-3355inj group and 98.0% (50/51) in the ceftriaxone group.
【Results of safety】
Incidence of adverse events was 72.8% (99/136, 340 events) in theDR-3355inj group and 71.5% (88/123, 275 events) in the ceftriaxone
group.
The incidence of adverse drug reactions was 53.7% (73/136, 223events) in the DR-3355inj group and 56.9% (70/123, 150 events) in theceftriaxone group.
【Conclusions】
The clinical response at completion/discontinuation of treatment(success rate) of the DR-3355inj group was 88.5% (92/104). Because
the lower limit of the 95% confidence interval of the intergroupdifference with the ceftriaxone group exceeded -10%, non-inferiorityof DR-3355 to ceftriaxone was confirmed. No clinically relevant
safety problems were observed with DR-3355 injection. Intravenous
administration of DR-3355 500 mg once daily for 7 to 14 days istherefore considered to demonstrate sufficient therapeutic effect forcommunity-acquired pneumonia (bacterial pneumonia) in adults.

Date of Report

Jun 1, 2010