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

Sponsor

Astellas Pharma Europe B.V. (Industry)

Overall Status

Completed

CT.gov ID

NCT01604928

Collaborator

(none)

260

Enrollment

Locations

Arms

Duration (Months)

8.7

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Urinary Bladder, Overactive	Drug: YM178 Drug: tolterodine Drug: Placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

260 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

A Randomized, Double-blind, Parallel Group, Proof of Concept Study of YM178 in Comparison With Placebo and Tolterodine in Patients With Symptomatic Overactive Bladder

Study Start Date :

Apr 1, 2004

Actual Primary Completion Date :

Jan 1, 2005

Actual Study Completion Date :

Jan 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: YM178 Dose 1 low dose	Drug: YM178 Oral Other Names: mirabegron
Experimental: YM178 Dose 2 high dose	Drug: YM178 Oral Other Names: mirabegron
Active Comparator: Tolterodine Oral	Drug: tolterodine Oral Other Names: Detrusitol
Placebo Comparator: Placebo Oral	Drug: Placebo Oral

Outcome Measures

Primary Outcome Measures

Change from baseline in mean number of micturitions per 24 hours [Baseline and 4 weeks (end of treatment)]

Secondary Outcome Measures

Change from baseline in mean number of urgency episodes/24 hours [Baseline and 4 weeks (end of treatment)]
Change from baseline in mean volume voided per micturition [Baseline and 4 weeks (end of treatment)]
Change from baseline in mean number of urge incontinence episodes/24 hours [Baseline and 4 weeks (end of treatment)]
Change from baseline in mean number of incontinence episodes/24 hours [Baseline and 4 weeks (end of treatment)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

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)

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Site: 12	Brussels	Belgium	1090
2	Site: 13	Edegem	Belgium	2650
3	Site: 11	Gent	Belgium	9000
4	Site: 10	Leuven	Belgium	3000
5	Site: 25	Melnik	Czech Republic	276 01
6	Site: 22	Prague	Czech Republic	128 08
7	Site: 24	Prague	Czech Republic	140 59
8	Site: 20	Prague	Czech Republic	180 81
9	Site: 21	Usti nad Labem	Czech Republic	40001
10	Site: 23	Usti nad Labem	Czech Republic	401 13
11	Site: 32	Bad Ems	Germany	56130
12	Site: 30	Emmendingen	Germany	79312
13	Site: 35	Frankfurt	Germany	60326
14	Site: 34	Hagenow	Germany	19230
15	Site: 33	Hamburg	Germany	20253
16	Site: 36	Koblenz	Germany	56068
17	Site: 31	Trier	Germany	54290
18	Site: 42	Alzira-Valencia	Spain	46600
19	Site: 40	Madrid	Spain	28046
20	Site: 43	Miranda de Ebro	Spain	09200
21	Site: 55	Gotenburg	Sweden	413 45
22	Site: 53	Linkoping	Sweden	582 24
23	Site: 50	Lund	Sweden	221 85
24	Site: 51	Stockholm	Sweden	141 86
25	Site: 52	Uppsala	Sweden	751 85
26	Site: 64	Bimingham	United Kingdom	B15 2TG
27	Site: 62	London	United Kingdom	N19 5LW
28	Site: 63	London	United Kingdom	W1P 7PN
29	Site: 60	Sheffield	United Kingdom	S10 2JF
30	Site: 61	Swansea	United Kingdom	SA6 6NL