Study to Test the Efficacy and Safety of YM178 in Subjects With Symptoms of Overactive Bladder

NCT ID: NCT01604928

Last Updated: 2024-10-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-04-05
• Study Completion Date: 2005-01-25

Brief Summary

The study is intended to test efficacy, safety and tolerability of two doses of YM178 against placebo and tolterodine to treat patients with symptoms of over active bladder.

Detailed Description

This is a multinational, multicenter, double-blind, double-dummy,

randomized, parallel group, placebo and active controlled phase II proof-of concept study. Patients are enrolled into a single-blind, 2-week placebo run in

period after which they are randomized to 4 weeks of double-blind

treatment with YM178 (low dose and high dose), placebo or tolterodine. Subsequently patients will be followed for an additional 2 weeks

with single-blind placebo treatment. There are 6 visits in total: visit 1 at

enrolment, visit 2 (baseline) after the 2-week placebo run-in, visits 3, 4 and 5

after 1, 2 and 4 weeks of double-blind treatment respectively, and visit 6

after a 2-week follow-up.

Conditions

Urinary Bladder, Overactive

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

YM178 Dose 1

low dose

Group Type: EXPERIMENTAL

YM178

Intervention Type: DRUG

Oral

YM178 Dose 2

high dose

Group Type: EXPERIMENTAL

YM178

Intervention Type: DRUG

Oral

Tolterodine

Oral

Group Type: ACTIVE_COMPARATOR

tolterodine

Intervention Type: DRUG

Oral

Placebo

Oral

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Oral

Interventions

YM178

Oral

Intervention Type: DRUG

tolterodine

Oral

Intervention Type: DRUG

Placebo

Oral

Intervention Type: DRUG

Other Intervention Names

mirabegron; Detrusitol

Eligibility Criteria

Inclusion Criteria

• Patient is willing and able to complete the micturition diary correctly.
• Symptoms of overactive bladder (urinary frequency and urgency with or without incontinence) for ≥ 3 months

At randomization:

• Patient must experience frequency of micturition on average ≥ 8 times per 24-hour period during the 3-day micturition diary period
• Patient must experience at least 3 episodes of urgency (grade 3 or 4) with or without incontinence, during the 3-day micturition diary period

Exclusion Criteria

• Pregnant women or women who intend to become pregnant during the study or women of childbearing potential who are sexually active and practicing an unreliable method of birth control or will be lactating during the study. Reliable contraceptive methods are intra-uterine devices, contraceptive pills of combination type, hormonal implants, contraceptive patches and injectable contraceptives
• Clinically significant outflow obstruction (at the discretion of the investigator)
• Significant post void residual volume (PVR>200ml)
• Significant stress incontinence or mixed stress/urge incontinence where stress is the predominant factor as determined by the investigator (for female patients confirmed by a cough provocation test)
• Patients with a neurological cause for abnormal detrusor activity
• Diabetic neuropathy
• Evidence of a symptomatic urinary tract infection, chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs
• Uncontrolled narrow angle glaucoma, urinary or gastric retention, colitis ulcerosa, toxic megacolon, myasthenia gravis or any other medical condition which in the opinion of the investigator makes the use of anticholinergics contra-indicated
• Non-drug treatment including electrostimulation therapy

(a bladder training program or pelvic floor exercises which started more than 1 month prior to entry into the study can be continued)

• Use of medications intended to treat urinary incontinence or listed in Appendix 1 Part A. Part B lists medications that are restricted but accepted under certain conditions
• Known or suspected hypersensitivity to tolterodine, other anticholinergics, ß-adrenoceptor agonists, or lactose or any of the other inactive ingredients
• Any clinically significant cardiovascular complication including CVA, recent myocardial infarction and uncontrolled hypertension, indicated by a sitting systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 110 mmHg
• Any clinically significant condition, which in the opinion of the investigator makes the patient unsuitable for the trial
• Participation in any clinical trial within 30 (90 in the UK) days prior to randomization
• Employees of the sponsor, third parties associated with the study, or the study site

At randomization:

• Patient who did not complete the micturition diary according to the instructions
• Average total daily urine volume > 3000 ml as recorded in the micturition diary
• Clinically significant elevation of serum creatinine or liver enzymes as evidenced by creatinine >150 mmol/L, ASAT or ALAT > 2x upper limit of normal range (ULN), γ-GT > 3x ULN and/or abnormal serum total bilirubin (as assessed in visit 1 samples or alternative sampling within 4 weeks prior to visit 1)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma Europe B.V.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Study Manager

Role: STUDY_DIRECTOR

Astellas Pharma Europe B.V.

Locations

Site: 12

Brussels, , Belgium

Site: 13

Edegem, , Belgium

Site: 11

Ghent, , Belgium

Site: 10

Leuven, , Belgium

Site: 25

Mělník, , Czechia

Site: 22

Prague, , Czechia

Site: 24

Prague, , Czechia

Site: 20

Prague, , Czechia

Site: 21

Ústí nad Labem, , Czechia

Site: 23

Ústí nad Labem, , Czechia

Site: 32

Bad Ems, , Germany

Site: 30

Emmendingen, , Germany

Site: 35

Frankfurt, , Germany

Site: 34

Hagenow, , Germany

Site: 33

Hamburg, , Germany

Site: 36

Koblenz, , Germany

Site: 31

Trier, , Germany

Site: 42

Alzira-Valencia, , Spain

Site: 40

Madrid, , Spain

Site: 43

Miranda de Ebro, , Spain

Site: 55

Gothenburg, , Sweden

Site: 53

Linköping, , Sweden

Site: 50

Lund, , Sweden

Site: 51

Stockholm, , Sweden

Site: 52

Uppsala, , Sweden

Site: 64

Bimingham, , United Kingdom

Site: 62

London, , United Kingdom

Site: 63

London, , United Kingdom

Site: 60

Sheffield, , United Kingdom

Site: 61

Swansea, , United Kingdom

Countries

Belgium; Czechia; Germany; Spain; Sweden; United Kingdom

References

Chapple CR, Amarenco G, Lopez Aramburu MA, Everaert K, Liehne J, Lucas M, Vik V, Ridder A, Snijder R, Yamaguchi O; BLOSSOM Investigator Group. A proof-of-concept study: mirabegron, a new therapy for overactive bladder. Neurourol Urodyn. 2013 Nov;32(8):1116-22. doi: 10.1002/nau.22373. Epub 2013 Feb 19.

Reference Type: DERIVED

PMID: 23424164 (View on PubMed)

Related Links

https://www.astellasclinicalstudyresults.com/hcp/study.aspx?ID=194

Link to results on Astellas Clinical Study Results website

Other Identifiers

178-CL-008

Identifier Type: -

Identifier Source: org_study_id