Study to Test the Long Term Safety and Efficacy of the Beta-3 Agonist Mirabegron (YM178) in Patients With Symptoms of Overactive Bladder (TAURUS)

Astellas

Status and phase: Completed; Phase 3

Conditions: Urinary Bladder, Overactive

Treatments: Drug: Mirabegron; Drug: Placebo to Mirabegron; Drug: Placebo to Tolterodine; Drug: Tolterodine

Study type: Interventional

Funder types: Industry

Identifiers

NCT00688688

2007-001452-39 (EudraCT Number)

178-CL-049

Details and patient eligibility

About

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.

Full description

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

Enrollment: 2,792 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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2,792 participants in 3 patient groups

Mirabegron 50 mg

Experimental group

Description:

Participants received mirabegron 50 mg tablets and matching tolterodine extended release (ER) placebo capsules orally once a day for 12 months.

Treatment:

Drug: Placebo to Tolterodine

Drug: Mirabegron

Mirabegron 100 mg

Experimental group

Description:

Participants received mirabegron 100 mg tablets and matching tolterodine ER placebo capsules orally once a day for 12 months.

Treatment:

Drug: Placebo to Tolterodine

Drug: Mirabegron

Tolterodine ER 4 mg

Active Comparator group

Description:

Participants received tolterodine ER 4 mg capsules and matching mirabegron placebo tablets orally once a day for 12 months.

Treatment:

Drug: Tolterodine

Drug: Placebo to Mirabegron