SYNOPSIS
Name of Sponsor/Company
Name of Finished ProductName of Active Ingredient
Title of Study
Investigators
Study Centre(s)Publication (reference)
Studied Period
Phase of Development
Objectives

Methodology
Number of Patients(planned and analyzed)

Daiichi Sankyo Co., Ltd.
CRAVIT ® INTRAVENOUS DRIP INFUSION
Levofloxacin
Comparative study of DR-3355 injection and pazufloxacin injection
in patients with urinary tract infection
61 sites
None
Date of obtaining first consent: May, 2012
Date of last observation: February, 2014
Phase 3The purpose of this study is to compare the bacteriological efficacy
and safety of DR-3355 injection and pazufloxacin (PZFX) injection
on urinary tract infection at the end of intravenous treatment, and toverify the non-inferiority of DR-3355 injection to PZFX injection.
Additionally, the efficacy and safety is evaluated after switching from
DR-3355 injection to levofloxacin (LVFX) oral agent.
Open-label, multicentre, randomized study
Planned: 324 patients
Registered: 325 patients (DR-3355 group: 162 patients, PZFX group:
163 patients)
Analyzed:
Per protocol set (PPS)
Evaluation of safety

Diagnosis and Main Criteria
for Inclusion

Test Product, Dose andMode of Administration,
Batch Number

Duration of Treatment
Reference Therapy, Doseand Mode ofAdministration, Batch
Number

252 patients (DR-3355 group: 127 patients, PZFX
group: 125 patients)
324 patients (DR-3355 group: 162 patients, PZFX
group: 162 patients)

Diagnosis:
Urinary tract infection (acute uncomplicated pyelonephritis,complicated pyelonephritis, complicated cystitis)
Inclusion:
1) Patients between the ages of 20 to 79 at the time of obtaining
informed consents.
2) Patients who require hospitalization at the time of enrollment.
3) Patients with symptoms of pyelonephritis or cystitis.
4) Patients who meet the criteria for pyuria and have bacteria in theurine5) Patients who require an injection treatment.(any of the following
symptoms: temperature of 38°C or more, nausea or vomiting,dehydration, suspicion of bacteremia, urine flow disorder,anorexia, diarrhea)
Test product (batch number):
DR-3355 injection (D3355I0H11T01A)
Oral LVFX (D3355F0S11T01A)
Dosage and administration:
Intravenous administration of DR-3355inj at 500 mg, once daily
Oral administration of LVFX at 500 mg, once daily
Intravenous therapy for 5 days could be followed by LVFX for 5days.
Control drug (batch number):
PZFX injection (D3355I0H11T02A)
Oral LVFX (D3355F0S11T01A)
Dosage and administration:
Intravenous administration of PZFX inj at 500 mg, twice daily

Criteria for Evaluation

Statistical Method

Summary - Conclusion

Date of Report

Oral administration of LVFX at 500 mg, once daily
Primary endpoint:
Bacteriological efficacy at the end of intravenous treatment (PPS)
Secondary endpoint:Clinical efficacy at the end of intravenous treatment (PPS)
Clinical efficacy and bacteriological efficacy at the test of cure
Clinical efficacy and bacteriological efficacy at the evaluation ofrecurrence
Bacteriological response by causative bacteria
Antipyretic potency
As the primary endpoint, the point estimate and the two-sided 95%
confidence interval (CI) based on the normal approximation were
estimated for the difference in bacteriological efficacy between theDR-3355 group and the PZFX group at the end of intravenoustreatment.
When the lower limit of the two-sided 95% CI was above −10%, it
was judged that non-inferiority of the DR-3355 group to the PZFX
group was confirmed.
Efficacy summary:The bacteriological efficacy rate at the end of intravenous
treatment was 93.7% (119/127, 95% CI: 89.5 to 97.9) in theDR-3355 group, 89.5% (111/124, 95% CI: 84.1 to 94.9) in thePZFX group, and the between-group difference was 4.2% (95% CI:−2.7 to 11.0). The lower limit of 95% CI of the between-groupdifference was above the non-inferiority margin (−10%),
non-inferiority of DR-3355 versus PZFX was confirmed.
Switch therapy from DR-3355 injection to LVFX oral agent
showed the comparable therapeutic effect in switch therapy fromPZFX injection to LVFX oral agent.
Safety summary:
The incidence of adverse events up to the end of intravenous
treatment was 44.4% (72/162, 95% CI: 36.8 to 52.1) in theDR-3355 group, 45.1% (73/162, 95% CI: 37.4 to 52.7) in thePZFX group. The between-group difference was −0.6% (95% CI:−11.4 to 10.2), no clinically significant difference was observed
between the groups.
The incidence of adverse drug reactions up to the end of
intravenous treatment was 30.2% (49/162, 95% CI: 23.2 to 37.3) inthe DR-3355 group, 26.5% (43/162, 95% CI: 19.7 to 33.3) in thePZFX group. The between-group difference was 3.7% (95% CI:−6.1 to 13.5), no clinically significant difference was observed
between the groups.
There was no difference in the type and incidence of adverse
events by severity, adverse event that led to withdrawal between
the groups. No adverse events that were considered related to thestudy drug reported among the serious adverse events in the bothgroups.
Conclusion:
From these results, DR-3355 injection is useful for treatment ofacute uncomplicated pyelonephritis, complicated pyelonephritis, orcomplicated cystitis, and there is no important problem in thesafety.
December, 2014