Clinical trial NCT00689104: Study to Assess the Efficacy and Safety of the Beta-3 Agonist Mirabegron (YM178) in Patients With Symptoms of Overactive Bladder
Official title: A Randomized, Double-Blind, Parallel Group, Placebo and Active Controlled, Multicenter Study to Assess the Efficacy and Safety of Mirabegron in Subjects With Symptoms of Overactive Bladder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Urinary Bladder, Overactive
Keywords: Micturition
Urinary incontinence
Urinary urge incontinence
Overactive bladder (OAB)
Urgency
YM178
Frequency
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2008-06-03
Enrollment: 2336
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is intended to test efficacy, safety and tolerability of two doses of Mirabegron against placebo and compare the efficacy and safety with active comparator in patients with symptoms of overactive bladder.


Eligibility criteria: Inclusion Criteria:

* Subject is willing and able to complete the micturition diary and questionnaires correctly
* Subject has symptoms of overactive bladder (urinary frequency and urgency with or without urge incontinence) for ≥ 3 months
* Subject experiences frequency of micturition on average ≥ 8 times per 24-hour period during the 3-day micturition diary period
* Subject 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:

* Subject is breastfeeding, pregnant, intends to become pregnant during the study, or of childbearing potential, sexually active and not practicing a highly reliable method of birth control
* Subject has significant stress incontinence or mixed stress/urge incontinence where stress is the predominant factor
* Subject has an indwelling catheter or practices intermittent self-catheterization
* Subject has diabetic neuropathy
* Subject has 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
* Subject receives non-drug treatment including electro-stimulation therapy
* Subject has severe hypertension
* Subject has a known or suspected hypersensitivity to tolterodine, other anticholinergics, YM178, other beta-adrenoreceptor (ß-AR) agonists, or lactose or any of the other inactive ingredients
* Subject has been treated with any investigational drug or device within 30 days (90 days in the UK)
* Subject had an average total daily urine volume \> 3000 mL as recorded in the 3-day micturition diary period
* Subject has serum creatinine \>150 umol/L, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 2x upper limit of normal range (ULN), or gamma glutamyl transferase (γ-GT) \> 3x ULN
* Subject has a clinically significant abnormal electrocardiogram (ECG)

Primary outcomes:
measure: Change From Baseline to End of Treatment (Final Visit) in Mean Number of Incontinence Episodes Per 24 Hours
timeFrame: Baseline and Week 12 (final visit)
measure: Change From Baseline to End of Treatment (Final Visit) in Mean Number of Micturitions Per 24 Hours
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change From Baseline to Final Visit in Mean Volume Voided Per Micturition
timeFrame: Baseline and Week 12
measure: Change From Baseline to Week 4 in Mean Number of Incontinence Episodes Per 24 Hours
timeFrame: Baseline and Week 4
measure: Change From Baseline to Week 4 in Mean Number of Micturitions Per 24 Hours
timeFrame: Baseline and Week 4
measure: Change From Baseline to Week 8 and Week 12 in Mean Number of Incontinence Episodes Per 24 Hours
timeFrame: Baseline and Weeks 8 and 12
measure: Change From Baseline to Week 8 and Week 12 in Mean Number of Micturitions Per 24 Hours
timeFrame: Baseline and Weeks 8 and 12
measure: Change From Baseline to Week 4, Week 8 and Week 12 in Mean Volume Voided Per Micturition
timeFrame: Baseline and Weeks 4, 8 and 12
measure: Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours
timeFrame: Baseline and Weeks 4, 8 and 12
measure: Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Urgency Episodes (Grades 3 or 4) Per 24 Hours
timeFrame: Baseline and Weeks 4, 8 and 12
measure: Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Level of Urgency
timeFrame: Baseline and Weeks 4, 8 and 12
measure: Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours
timeFrame: Baseline and Weeks 4, 8 and 12
measure: Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Mean Number of Pads Used Per 24 Hours
timeFrame: Baseline and Weeks 4, 8 and 12
measure: Percentage of Participants With Zero Incontinence Episodes at Week 4, Week 8, Week 12 and the Final Visit
timeFrame: Weeks 4, 8 and 12
measure: Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Weeks 4, 8, 12 and the Final Visit
timeFrame: Baseline and Weeks 4, 8 and 12
measure: Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Symptom Bother Score
timeFrame: Baseline and Weeks 4, 8 and 12
measure: Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score
timeFrame: Baseline and Weeks 4, 8 and 12
measure: Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed
timeFrame: Baseline and Week 12
measure: Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working
timeFrame: Baseline and Week 12
measure: Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment
timeFrame: Baseline and Week 12
measure: Change From Baseline to Week 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment
timeFrame: Baseline and Week 12
measure: Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score
timeFrame: Baseline and Week 12
measure: Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-care Score
timeFrame: Baseline and Week 12
measure: Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score
timeFrame: Baseline and Week 12
measure: Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score
timeFrame: Baseline and Week 12
measure: Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D)Anxiety/Depression Score
timeFrame: Baseline and Week 12
measure: Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS)
timeFrame: Baseline and Weeks 4, 8 and 12
measure: Change From Baseline to Week 12 and Final Visit in Patient Perception of Bladder Condition (PPBC)
timeFrame: Baseline and Week 12
measure: Change From Baseline to Week 12 and Final Visit in Treatment Satisfaction on Visual Analog Scale (TS-VAS)
timeFrame: Baseline and Week 12
measure: Change From Baseline to Week 4, Week 8, Week 12 and Final Visit in Number of Non-study Related Visits to Physician
timeFrame: Baseline and Weeks 4, 8 and 12
measure: Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC) at Week 12 and Final Visit
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
city: Auchenflower
country: Australia
city: Clayton
country: Australia
city: Kogarah
country: Australia
city: Randwick
country: Australia
city: Woolloongabba
country: Australia
city: Graz
country: Austria
city: Innsbruck
country: Austria
city: Linz
country: Austria
city: Minsk
country: Belarus
city: Minsk
country: Belarus
city: Minsk
country: Belarus
city: Antwerp
country: Belgium
city: Antwerp
country: Belgium
city: Brussels
country: Belgium
city: Brussels
country: Belgium
city: Edegem
country: Belgium
city: Gent
country: Belgium
city: Kortrijk
country: Belgium
city: Leper
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Sint Truiden
country: Belgium
city: Pleven
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Brno
country: Czechia
city: Melnik
country: Czechia
city: Olomouc
country: Czechia
city: Ostrava-Poruba
country: Czechia
city: Plzen
country: Czechia
city: Prague
country: Czechia
city: Prague
country: Czechia
city: Prague
country: Czechia
city: Steti
country: Czechia
city: Usti nad Labem
country: Czechia
city: Aalborg
country: Denmark
city: Aarhus
country: Denmark
city: Glostrup
country: Denmark
city: Roskilde
country: Denmark
city: Helsinki
country: Finland
city: Oulu
country: Finland
city: Tampere
country: Finland
city: Turku
country: Finland
city: Bordeaux
country: France
city: Colmar
country: France
city: Marseille Cedex 9
country: France
city: Marseille
country: France
city: Mulhouse
country: France
city: Nantes
country: France
city: Nimes Cedex 9
country: France
city: Orleans Cedex 2
country: France
city: Paris-Cedex 12
country: France
city: Paris
country: France
city: Rouen
country: France
city: Saint Priest en Jarez
country: France
city: Strasbourg
country: France
city: Toulouse Cedex 9
country: France
city: Aichach
country: Germany
city: Bad Ems
country: Germany
city: Bautzen
country: Germany
city: Berlin
country: Germany
city: Duisburg
country: Germany
city: Frankfurt
country: Germany
city: Ganderkesee
country: Germany
city: Hagenow
country: Germany
city: Halle/Saale
country: Germany
city: Hamburg
country: Germany
city: Henningsdorf
country: Germany
city: Hettstedt
country: Germany
city: Koblenz
country: Germany
city: Leipzig
country: Germany
city: Lutherstadt Eisleben
country: Germany
city: Muenchen-Bogenhausen
country: Germany
city: Neustadt I. Sachsen
country: Germany
city: Oranienburg
country: Germany
city: Radebeul
country: Germany
city: Sangerhausen
country: Germany
city: Trier
country: Germany
city: Uetersen
country: Germany
city: Athens
country: Greece
city: Nikaias-Piraeus
country: Greece
city: Patras
country: Greece
city: Thessaloniki
country: Greece
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Eger
country: Hungary
city: Nyiregyhaza
country: Hungary
city: Papa
country: Hungary
city: Sopron
country: Hungary
city: Szeged
country: Hungary
city: Szekesfehervar
country: Hungary
city: Szekszard
country: Hungary
city: Tatabanya
country: Hungary
city: Veszprem
country: Hungary
city: Reykjavik
country: Iceland
city: Cork
country: Ireland
city: Dublin 9
country: Ireland
city: Dublin
country: Ireland
city: Mullingar
country: Ireland
city: Tralee
country: Ireland
city: Bari
country: Italy
city: Catanzaro
country: Italy
city: Florence
country: Italy
city: Florence
country: Italy
city: Genoa
country: Italy
city: Latina
country: Italy
city: Magenta
country: Italy
city: Milan
country: Italy
city: Milan
country: Italy
city: Modena
country: Italy
city: Naples
country: Italy
city: Perugia
country: Italy
city: Teramo
country: Italy
city: Treviglio
country: Italy
city: Varese
country: Italy
city: Liepaja
country: Latvia
city: Riga
country: Latvia
city: Kaunas
country: Lithuania
city: Vilnius
country: Lithuania
city: Amsterdam
country: Netherlands
city: Apeldoorn
country: Netherlands
city: Apeldoorn
country: Netherlands
city: Eindhoven
country: Netherlands
city: Enschede
country: Netherlands
city: Leiden
country: Netherlands
city: Maastricht
country: Netherlands
city: Nijmegen
country: Netherlands
city: Sneek
country: Netherlands
city: Tilburg
country: Netherlands
city: Winterswijk
country: Netherlands
city: Bergen
country: Norway
city: Drammen
country: Norway
city: Hamar
country: Norway
city: Oslo
country: Norway
city: Tonsberg
country: Norway
city: Bialystok
country: Poland
city: Chorzow
country: Poland
city: Lodz
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Warsaw
country: Poland
city: Warsaw
country: Poland
city: Warsaw
country: Poland
city: Wroclaw
country: Poland
city: Amadora
country: Portugal
city: Porto
country: Portugal
city: Tomar
country: Portugal
city: Viana do Castelo
country: Portugal
city: Bucharest
country: Romania
city: Bucharest
country: Romania
city: Lasi
country: Romania
city: Oradea
country: Romania
city: Timisoara
country: Romania
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Martin
country: Slovakia
city: Poprad
country: Slovakia
city: Skalica
country: Slovakia
city: Trencin
country: Slovakia
city: Zilina
country: Slovakia
city: Bloemfontein
country: South Africa
city: Hatfield
country: South Africa
city: Lyttelton
country: South Africa
city: Paarl
country: South Africa
city: Pietermaritzburg
country: South Africa
city: Barcelona
country: Spain
city: Bilbao
country: Spain
city: Esplugues De Llobregat-Barcelo
country: Spain
city: Fuenlabrada
country: Spain
city: Getafe
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Mataro
country: Spain
city: Miranda de Ebro
country: Spain
city: Palma de Mallorca
country: Spain
city: Sevilla
country: Spain
city: Toledo
country: Spain
city: Valencia
country: Spain
city: Villareal
country: Spain
city: Boras
country: Sweden
city: Helsingborg
country: Sweden
city: Orebro
country: Sweden
city: Skovde
country: Sweden
city: Stockholm
country: Sweden
city: Stockholm
country: Sweden
city: Stockholm
country: Sweden
city: Stockholm
country: Sweden
city: Umea
country: Sweden
city: Uppsala
country: Sweden
city: Frauenfeld
country: Switzerland
city: Luzern
country: Switzerland
city: Kiev
country: Ukraine
city: Kiev
country: Ukraine
city: Birmingham
country: United Kingdom
city: Chorley
country: United Kingdom
city: Croydon
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
country: United Kingdom
city: London
country: United Kingdom
city: Manchester
country: United Kingdom
city: Newcastle Upon Tyne
country: United Kingdom
city: Northwood
country: United Kingdom
city: Reading
country: United Kingdom
city: Reading
country: United Kingdom
city: Sheffield
country: United Kingdom
city: Swansea
country: United Kingdom
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Central Contact
role: STUDY_DIRECTOR
References:
citation: Khullar V, Amarenco G, Angulo JC, Cambronero J, Hoye K, Milsom I, Radziszewski P, Rechberger T, Boerrigter P, Drogendijk T, Wooning M, Chapple C. Efficacy and tolerability of mirabegron, a beta(3)-adrenoceptor agonist, in patients with overactive bladder: results from a randomised European-Australian phase 3 trial. Eur Urol. 2013 Feb;63(2):283-95. doi: 10.1016/j.eururo.2012.10.016. Epub 2012 Nov 6.
citation: Desroziers K, Aballea S, Maman K, Nazir J, Odeyemi I, Hakimi Z. Estimating EQ-5D and OAB-5D health state utilities for patients with overactive bladder. Health Qual Life Outcomes. 2013 Nov 19;11:200. doi: 10.1186/1477-7525-11-200.