SYNOPSIS
Name ofDaiichi Sankyo Co., Ltd.

Sponsor/Company
Name of Finished Product

SONAZOID® 16 µL vial for injection

Name of Active Ingredient

perflubutane

Title of Study

DD-723 Phase II Clinical Trial- Dose-response study in patients with suspected prostatecancer -Investigators

4 investigators

Study Centre(s)4 centers

Publication (reference)

Uemura H, Sano F, Nomiya A, et al. Usefulness of
perflubutane

microbubble-enhanced

ultrasoundin

imaging and detection of prostate cancer: phase II
multicenter clinical trial. World Journal of Urology, 2013,31(5): 1123-1128.
Studied Period

9 months (March 2009 -December 2009 )Phase of Development

Phase II

Objectives

Examination of the recommended dose based on thedose-response relationship, by assessing the contrast
effect, as well as safety of DD-723 in subjects withsuspected prostate cancer.

Methodology

Multicenter, randomized, and single-blind controlled trial:
Dose-response study on three doses, parallel group, andblindedassessment

by

threeindependent

blindedreviewers with respect to images that were randomized
the order of assessment.
Number of Patients

Planned: 75 subjects（60 subjects for efficacy assessment,(planned and analyzed)

15 subjects for training and inter-rater reliability
confirmation）
Treatment: 75 subjects
Analyzed: 58 subjects
Training and inter-rater reliability confirmation：15
subjects

Diagnosis and Main

1) Subjects with suspected prostate cancer

Criteria for Inclusion2) Subjects whose most recent PSA level is between 4.0
ng/mL and 20 ng/mL3) Subjects aged between 20 and 80 years at the time ofinformed consent
Test Product, Dose andA single dose of 0.024 µL MB/kg, 0.12 µL MB/kg, or 0.36

Mode of Administration,µL MB/kg delivered via a forearm vein

Batch Number

Lot number: DD723L0S08T01A

Duration of Treatment

Single injection

Reference Therapy, DoseN.A.

andModeofAdministration,

Batch

NumberCriteria for Evaluation

Rate showed enough imaging effect by blinded reviewers:
Results of multiple evaluations by three blinded
reviewers were used to assess as the primary endpoint.

Statistical Method

The main target groups for the efficacy analysis was PPS,
and the dose-response relationship of the efficacy rate oftheoverall

contrast

contrast-enhanced

effectwasultrasonographyevaluatedininbyPPS

Cochran-Armitage test using contrast coefficient (-2,1,1).
Summary - Conclusion

The primary endpoint was assessed in the efficacy
analysis set, which comprised 58 (low dose group: 20subjects, intermediate dose group: 20 subjects, high dosegroup: 18 subjects) of the 75 patients (low dose group: 27subjects, intermediate dose group: 25 subjects, high dosegroup: 23 subjects).
The efficacy rates in the overall contrast effect were 35.0%(7/20, 95%CI: 14.1 - 55.9) in the low dose group, 95.0%（19/20, 95%CI: 85.4 -100.0） in the intermediate dosegroup, and 77.8%（14/18, 95%CI:58.6 - 97.0） in the highdose group, respectively. That means that the highest
efficacy rate was showed in the intermediate dose of 0.12
µL MB/kg and also it was saturated in the intermediate
dose [Cochrane–Armitage test using contrast coefficients(-2, 1, 1): P<0.001].
Analysis of safety revealed no dose-dependence in terms of
the incidence of adverse events, and all of the adverse
events that occurred were mild.

Date of Report

Sep, 2014