UMIN-CTR Clinical Trial

Public title

A Double-Blind, Single-Dose, 2-period Crossover Exploratory Study to Evaluate the Effects of Single Oral Dose of Duloxetine on Urethral Pressure in Japanese Female Patients with Stress Urinary Incontinence

Acronym

A Double-Blind, Single-Dose, 2-period Crossover Exploratory Study to Evaluate the Effects of Single Oral Dose of Duloxetine on Urethral Pressure in Japanese Female Patients with Stress Urinary Incontinence

Scientific Title

A Double-Blind, Single-Dose, 2-period Crossover Exploratory Study to Evaluate the Effects of Single Oral Dose of Duloxetine on Urethral Pressure in Japanese Female Patients with Stress Urinary Incontinence

Scientific Title:Acronym

A Double-Blind, Single-Dose, 2-period Crossover Exploratory Study to Evaluate the Effects of Single Oral Dose of Duloxetine on Urethral Pressure in Japanese Female Patients with Stress Urinary Incontinence

Region

Japan

Condition

Stress urinary incontinence

Classification by specialty

Urology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

The objective of this exploratory study is to evaluate the effects of single oral dose of duloxetine on urethral pressure under transcranial magnetic stimulation (TMS), sacral root magnetic stimulation (SMS) and cough stimulation in Japanese female patients with SUI, adopting a randomized double-blind single-dose 2-period crossover design

Basic objectives2

Pharmacodynamics

Basic objectives -Others

Trial characteristics_1

Exploratory

Trial characteristics_2

Developmental phase

Not applicable

Primary outcomes

-Intensity (threshold) of TMS causing urethral sphincter contraction (elevation in urethral pressure)
-Urethral pressure measured under SMS
-Urethral pressure measured under cough stimulation
-Leak Point Pressure (LPP)
-Volume of incontinence in the 20-minute pad test

Key secondary outcomes

Safety of magnetic stimulator, urodynamics equipment, and administration of Duloxetine.

Study type

Interventional

Basic design

Cross-over

Randomization

Randomized

Randomization unit

Individual

Blinding

Double blind -all involved are blinded

Control

Placebo

Stratification

NO

Dynamic allocation

NO

Institution consideration

Blocking

YES

Concealment

No need to know

No. of arms

2

Purpose of intervention

Prevention

Type of intervention

Medicine

Interventions/Control_1

Measurement of urethral, and bladder pressure in response to transcranial, sacral root magnetic and cough stimulation using micro-tip transducer catheter, before and after single oral administration of duloxetine hydrochloride (40 mg on a Duloxetine basis)

Interventions/Control_2

Measurement of urethral, and bladder pressure in response to transcranial, sacral root magnetic and cough stimulation using micro-tip transducer catheter, before and after single oral administration of placebo.

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

Not applicable

Gender

Female

Key inclusion criteria

At the time of screening
1.In the opinion of the primary investigator or the sub-investigator, the subject is capable of understanding and complying with protocol requirements.
2.The subject is a Japanese female patient with urinary incontinence, who signed the written informed consent, is not pregnant or lactating, and has prevailing symptoms of SUI.
3.The subject is aged 20 or higher at the time of signing the informed consent form.
4.The subject weights at least 45 kg and has BMI between 18.0 and 30.0 kg/m2, inclusive, at Screening.
5.The subject has no clinically significant abnormalities in accordance with the study site's criteria and is judged eligible to participate in this study by the investigator.
6.The subject presents symptoms of SUI beginning 3 months or more before consent acquisition.
7.The subject experiences SUI once or more per week.
8.The subject is positive in one-hour pad test.
9.A subject of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and 4 weeks (28 days) after the last dose of study medication.

On the day of medication
1.The subject presents symptoms of SUI beginning 3 months or more before consent acquisition.
2.The subject experiences SUI once or more per week

Key exclusion criteria

Subject who/with
-received study drug within 16 weeks before the study.
-is related to the study site or its employees, or may consent under duress.
-a history of disease considered to be unsuitable for the study.
-a history of convulsive disease and/or cardiac arrhythmias.
-carries an implant type medical device.
-an indwelling magnetic body in the cranial cavity.
-a history of gastrointestinal surgery that may affect the drug absorption, or a history of surgery for intrapelvic organ that may injure nerve related to lower urethra or other nerve.
-has chronic urinary tract infection or has had an episode within 4 weeks or evidence of current urinary tract infection.
-is hypersensitive to drugs including duloxetine and levofloxacin.
-has taken any medication that may affect the urinary tract function.
-has a history of alcohol abuse within 52 weeks prior and is unable to abstain from alcohol during the study.
-has a positive test result for HBsAg, HCV, HIV antibody/antigen or syphilis.
-smokes excessively routinely (unable to refrain from smoking during the hospitalization).
-has donated blood component within 2 weeks , or received blood collection in a volume exceeding 200 mL within 4 weeks or in a volume exceeding 400 mL within 12 weeks before hospitalization.
-has a history of drug therapy for urinary incontinence within 3 months.
-the pelvic floor muscles training has not stabilized or may not stabilize during the study period.
-is a patient with urinary incontinence in whom symptoms of urge incontinence are prevailing.
-has a supine blood pressure over 140 mm Hg for systolic, or 90 mm Hg for diastolic, or is taking medication for hypertention.
-is considered unsuitable for this study by the principal investigator or the sub-investigator.

Target sample size

10

Name of lead principal investigator

1st name
Middle name
Last name	Makoto Yono

Organization

Medical Co. LTA Nishikumamoto Hospital

Division name

Clinical Pharmacology Department

Zip code

Address

1012 Koga, Tomiai-machi, Minami-ku, Kumamoto-shi,Kumamoto 861-4157,Japan

TEL

096-358-1116

Email

m-yonou@nishikuma.com

Name of contact person

1st name
Middle name
Last name	Makoto Yono

Organization

Medical Co. LTA Nishikumamoto Hospital

Division name

Clinical Pharmacology Department

Zip code

Address

1012 Koga, Tomiai-machi, Minami-ku, Kumamoto-shi,Kumamoto 861-4157,Japan

TEL

096-358-1116

Homepage URL

Email

m-yonou@nishikuma.com

Institute

Medical Co. LTA Nishikumamoto Hospital

Institute

Department

Personal name

Organization

Takeda Pharmaceutical Company Limited

Organization

Division

Category of Funding Organization

Other

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Address

Tel

Email

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

医療法人相生会　にしくまもと病院（熊本県）

Date of disclosure of the study information

2013

Year

09

Month

17

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Single oral administration of duloxetine significantly increased the mean and maximal urethral pressures at rest over the proximal, middle and distal third of the urethra. During coughing, duloxetine significantly increased the mean distal urethral pressure.
All adverse events were mild and were resolved without further treatments.

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2013

Year

08

Month

14

Day

Date of IRB

Anticipated trial start date

2013

Year

09

Month

02

Day

Last follow-up date

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2013

Year

08

Month

31

Day

Last modified on

2014

Year

07

Month

08

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013582