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)

Diagnosis and Main Criteria
for Inclusion

Daiichi Sankyo Co., Ltd.
CRAVIT ® INTRAVENOUS DRIP INFUSION
Levofloxacin
Clinical trial of DR-3355 injection in patients with gynecologicalinfection
9 sites
None
Date of obtaining first consent: July, 2012
Date of last observation: October, 2013
Phase 3To evaluate the efficacy and safety in patients with gynecologicalinfection receiving a dose of 500 mg DR-3355 injection once a day.
To confirm the utility of switching therapy from DR-3355 injection tolevofloxacin oral agent.
Multicenter, Open-label study
Planned: 30 patients (As the patient that a bacteriological evaluationis possible: more than 15 subjects)
Registered: 23 patients
Analyzed:
Analysis set of efficacy (PPS) 19 subjects
Analysis set of bacteriological efficacy 18 subjects
Analysis set of PK 8 subjects
Analysis set of safety 22 subjects
Diagnosis: intrauterine infection, uterine adnexitis
Inclusion criteria:
1) Patients with age of 18 or older at the time of obtaining informedconsents
2) Inpatients or outpatients
3) Patients who meet the following criteria and have diagnosis of
intrauterine infection or uterine adnexitisa) Patients who have a fever of over 37.0°Cb) Patients who have lower abdominal pain (spontaneous pain orpressure pain)c) Patients who have at least one of the following- white blood cell count increase- C-reaction protein (CRP) level increase- presence of purulent vaginal discharge or secretory fluid- presence of pelvic abscess confirmed by an imaging test4) Patients with 14 points or more of clinical symptoms score
Exclusion criteria:
1) Pregnant or breastfeeding patients, patients who have thepossibility of being pregnant or patients who hope for cyesis in thestudy drug exposure period
2) Patients with a history of allergy or dermatological disorder toquinolone antibacterial agents.
3) Patients with severe nervous system disorder, severe cardiac
impairment, severe hepatic impairment, or severe renal impairment
4) Patients with infections caused by single pathogens which are
known to be resistant or ineffective to the study drug.
5) Patients administrated other antibacterial drugs within 7 days prior

Test Product, Dose andMode of Administration,
Batch Number

Duration of Treatment

Reference Therapy, Doseand Mode ofAdministration, Batch
NumberCriteria for Evaluation

Statistical Method
Summary - Conclusion

to the start of the test drug, and whose symptoms have shown
improvement.
6) Patients who have received levofloxacin, azithromycin, or otherantibacterial drugs (more than twice, except clinical failure
patients) within 7 days prior to the start of test drug administration.
7) Patients who require prohibited concomitant medications in thisstudy.
8) Patients who participated in any other clinical trials within theprevious 30 days.
9) Patients who have participated in the clinical trial of DR-3355
injection previously, and have been treated with the test drug.
10) Patients who are judged to be inappropriate by the investigator.
Test product (batch number):
DR-3355 injection (D3355I0H11T01A)
Oral levofloxacin (D3355F0S11T01A)
Dosage and administration:- Intravenous administration of DR-3355 injection at 500 mg, oncea day- Oral administration of levofloxacin at 500 mg, once a day
Three to fourteen days
DR-3355 injection (500 mg once daily for 60 min) was continuously
administered at least three days, with a switchover from intravenous
to oral levofloxacin (500 mg once daily) at the discretion of theinvestigator in accordance with clinical symptoms.
None

Primary endpoint: Clinical efficacy at the test of cure (TOC)
Secondary endpoint:- Clinical efficacy and bacteriological efficacy at the end oftreatment (EOT)- Bacteriological efficacy at the test of cure (TOC)
The point estimate of the efficacy rate and the two-sided 95%
confidence interval were calculated by diagnosis.
Efficacy summary:
The rate of clinical efficacy at TOC in the intrauterine infection anduterine adnexitis patients was 85.7% (6/7) and 80.0% (8/10),
respectively. The rate of bacterial eradication rate at TOC in theintrauterine infection and uterine adnexitis patients was 85.7% (6/7)
and 63.6% (7/11), respectively. The patients of switchover fromintravenous to oral agent in the intrauterine infection and uterine
adnexitis patients was 71.4% (5/7),75.0% (9/12), respectively. Except
for 1 patient in the uterine adnexitis, those patients were improvementall.
The vaginal discharge/plasma drug concentration ratio at two to six
hours after end of treatment of DR-3355 injection was 1.46.
Safety summary:
The incidence of adverse events was 76.2% (16/21) up to the TOC,
and 57.1% (12/21) up to the end of intravenous treatment. The
incidence of adverse drug reactions was 38.1% (8/21) up to the TOC,
and 23.8% (5/21) up to the end of intravenous treatment.
Conclusion:Date of Report

From these results, DR-3355 injection is useful for treatment ofintrauterine infection and uterine adnexitis, and there is no important
problem in the safety. In addition, it was confirmed the utility ofswitching therapy from DR-3355 injection to levofloxacin oral agent.
January 23, 2015