Clinical trial NCT00688688: Study to Test the Long Term Safety and Efficacy of the Beta-3 Agonist Mirabegron (YM178) in Patients With Symptoms of Overactive Bladder
Official title: A Randomized, Double-Blind, Parallel Group, Active Controlled, Multi-center Long-term Study to Assess the Safety and Efficacy of the Beta-3 Agonist Mirabegron (YM178) 50 mg qd and 100 mg qd in Subjects With Symptoms of Overactive Bladder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Urinary Bladder, Overactive
Keywords: Frequency
Overactive Bladder
Urgency
Urinary urge incontinence
Urinary incontinence
Micturition
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2008-06-03
Enrollment: 2792
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 the safety, tolerability, efficacy of two doses of long term once daily (qd) treatment of Mirabegron in patients with symptoms of overactive bladder and secondly to compare these with active comparator.

Detailed description: Patients who completed 178-CL-046 (NCT00689104) or 178-CL-047 (NCT00662909) or new patients could be enrolled in this study if eligible.

Eligibility criteria: Inclusion Criteria:

* Patient is willing and able to complete the micturition diary and questionnaires correctly
* Patient has symptoms of overactive bladder for ≥ 3 months
* Patient experiences 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:

* Patient 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
* Patient has significant stress incontinence or mixed stress/urge incontinence where stress is the predominant factor
* Patient has an indwelling catheter or practices intermittent self-catheterization
* Patient has diabetic neuropathy
* Patient 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
* Patient receives non-drug treatment including electro-stimulation therapy
* Patient has severe hypertension
* Patient 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
* Patient has been treated with any investigational drug or device within 30 days (90 days in the UK for all clinical studies except 178-CL-046)
* Patient had an average total daily urine volume \> 3000 mL as recorded in the 3-day micturition diary period
* Patient has serum creatinine \>150 umol/L, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 2x upper limit of normal range (ULN), or gamma-glutamyl transpeptidase (γ-GT) \> 3x ULN
* Patient has a clinically significant abnormal electrocardiogram (ECG)

Primary outcomes:
measure: Number of Participants With and Severity of Treatment-emergent Adverse Events (TEAEs)
timeFrame: From the first dose of double-blind study drug up until 30 days after the last dose of study drug, up to 13 months.
Secondary outcomes:
measure: Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Micturitions Per 24 Hours
timeFrame: Baseline and Months 1, 3, 6, 9 and 12
measure: Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Incontinence Episodes Per 24 Hours
timeFrame: Baseline and Months 1, 3, 6, 9 and 12
measure: Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Volume Voided Per Micturition
timeFrame: Baseline and Months 1, 3, 6, 9 and 12
measure: Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Incontinence Episodes Per 24 Hours
timeFrame: Baseline and Months 1, 3, 6, 9 and 12
measure: Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Urgency Episodes (Grade 3 and/or 4) Per 24 Hours
timeFrame: Baseline and Months 1, 3, 6, 9 and 12
measure: Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Level of Urgency
timeFrame: Baseline and Months 1, 3, 6, 9 and 12
measure: Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the Mean Number of Pads Used Per 24 Hours
timeFrame: Baseline and Months 1, 3, 6, 9 and 12
measure: Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Mean Number of Nocturia Episodes Per 24 Hours
timeFrame: Baseline and Months 1, 3, 6, 9 and 12
measure: Percentage of Participants With Zero Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit
timeFrame: Months 1, 3, 6, 9 and 12
measure: Percentage of Participants With ≥ 50% Reduction in Incontinence Episodes at Months 1, 3, 6, 9 and 12 and the Final Visit
timeFrame: Baseline and Months 1, 3, 6, 9 and 12
measure: Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Symptom Bother Score
timeFrame: Baseline and Months 1, 3, 6, 9 and 12
measure: Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in Health-related Quality of Life (HRQL) Total Score
timeFrame: Baseline and Months 1, 3, 6, 9 and 12
measure: Change From Baseline to Month 12 and Final Visit in Patient Perception of Bladder Condition (PPBC)
timeFrame: Baseline and Month 12
measure: Change From Baseline to Month 12 and Final Visit in Treatment Satisfaction-visual Analog Scale (TS-VAS)
timeFrame: Baseline and Month 12
measure: Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Work Time Missed
timeFrame: Baseline and Months 3, 6 and 12
measure: Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Impairment While Working
timeFrame: Baseline and Months 3, 6 and 12
measure: Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Overall Work Impairment
timeFrame: Baseline and Months 3, 6 and 12
measure: Change From Baseline to Months 3, 6, 12 and Final Visit in Work Productivity and Activity Impairment (WPAI): Percent Activity Impairment
timeFrame: Baseline and Months 3, 6 and 12
measure: Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Mobility Score
timeFrame: Baseline and Month 12
measure: Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Self-Care Score
timeFrame: Baseline and Month 12
measure: Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Usual Activities Score
timeFrame: Baseline and Month 12
measure: Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Pain/Discomfort Score
timeFrame: Baseline and Month 12
measure: Change From Baseline to Final Visit in European Quality of Life-5 Dimensions (EQ-5D) Anxiety/Depression Score
timeFrame: Baseline and Month 12
measure: Change From Baseline to Months 1, 3, 6, 9, 12 and Final Visit in the European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS)
timeFrame: Baseline and Months 1, 3, 6, 9 and 12
measure: Change From Baseline to Months 3, 6, 12 and Final Visit in Number of Non-study Related Visits to Physician
timeFrame: Baseline and Months 3, 6 and 12
measure: Percentage of Participants With Improvement in Patient Perception of Bladder Condition (PPBC)
timeFrame: Baseline and Month 12
measure: Safety as Assessed by Adverse Events (AEs), Vital Signs, Laboratory Tests, Physical Examination and Electrocardiogram
timeFrame: From the first dose of double-blind study drug up until 30 days after the last dose of study drug, up to 13 months.
Other outcomes:
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country: Portugal
city: Porto
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city: Tomar
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country: Romania
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country: Romania
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city: Moscow
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city: Moscow
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city: St Petersburg
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: Hatfield
country: South Africa
city: Lyttelton
country: South Africa
city: Paarl
country: South Africa
city: Pietermaritzburg
country: South Africa
city: Roodepoort
country: South Africa
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Bilbao
country: Spain
city: Getafe
country: Spain
city: Madrid
country: Spain
city: Madrid
country: Spain
city: Mataro
country: Spain
city: Miranda de Ebro
country: Spain
city: Sevilla
country: Spain
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country: Spain
city: Valencia
country: Spain
city: Huddinge
country: Sweden
city: Orebro
country: Sweden
city: Skovde
country: Sweden
city: Sonkoping
country: Sweden
city: Stockholm
country: Sweden
city: Stockholm
country: Sweden
city: Stockholm
country: Sweden
city: Umea
country: Sweden
city: Frauenfeld
country: Switzerland
city: Luzern
country: Switzerland
city: Kiev
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city: Kiev
country: Ukraine
city: Bristol
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city: Chorley
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city: Croydon
country: United Kingdom
city: Liverpool
country: United Kingdom
city: London
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city: London
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city: Manchester
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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: Chapple CR, Kaplan SA, Mitcheson D, Klecka J, Cummings J, Drogendijk T, Dorrepaal C, Martin N. Randomized double-blind, active-controlled phase 3 study to assess 12-month safety and efficacy of mirabegron, a beta(3)-adrenoceptor agonist, in overactive bladder. Eur Urol. 2013 Feb;63(2):296-305. doi: 10.1016/j.eururo.2012.10.048. Epub 2012 Nov 6.