A Study With Mirabegron 50 mg and 25 mg in Chinese Participants With Overactive Bladder
Condition: Urge Incontinence; Overactive Bladder (OAB)
MeSH terms: Urinary Bladder, Overactive; Urinary Incontinence, Urge
Intervention: mirabegron
Intervention description: Mirabegron was administered as single oral dose of 25 mg or 50 mg sustained-release tablet
Intervention MeSH terms: Mirabegron
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants fulfilling the screening inclusion/exclusion criteria were randomized in a 2:1 ratio, 50 mg mirabegron and 25 mg mirabegron, using a computer-generated randomization to reduce selection bias.
Masking: None (Open Label)
Masking description: This was an open label study.
Enrollment: 249.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: mirabegron

Summary:

      The purpose of this study was to evaluate the efficacy of mirabegron for the treatment of
      overactive bladder (OAB) in Chinese participants. This study also evaluated the safety of
      mirabegron for the treatment of OAB in Chinese participants, evaluated other efficacy
      variables of mirabegron for the treatment of OAB and explored different mirabegron starting
      doses.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participant should exhibit symptoms of OAB for at least 12 weeks before initiation of
             the screening period.

          -  Participant should have an average of ≥ 8 micturitions/24 hours.

          -  Participant should have an average of ≥ 1 episode of grade 3 or 4 (PPIUS) urgency or
             urgency incontinence/24 hours, during a 3-day micturition diary period.

          -  Female participant is not pregnant and at least one of the following conditions apply:

               -  Not a woman of childbearing potential (WOCBP)

               -  WOCBP who agrees to follow the contraceptive guidance from the time of informed
                  consent through at least 30 days after final investigational product (IP)
                  administration.

          -  Female participant must agree not to breastfeed starting at screening and throughout
             the study period and for 30 days after final IP administration.

          -  Female participant must not donate ova starting at first dose of investigational
             product (IP) and throughout the study period and for 30 days after final IP
             administration.

          -  Male participant with female partner(s) of childbearing potential (including
             breastfeeding partner) must agree to use contraception throughout the treatment period
             and 30 days after final IP administration.

          -  Male participant must not donate sperm during the treatment period and for 30 days
             after final IP administration.

          -  Male participant with pregnant partner(s) must agree to remain abstinent or use a
             condom for the duration of the pregnancy throughout the study period and for 30 days
             after final IP administration.

          -  Participant agrees not to participate in another interventional study while
             participating in the present study, defined as 28 days prior screening until
             completion of the last study visit.

        Exclusion Criteria:

        Exclusion at Visit 1/Week -2 (Screening)

          -  Participant has stress urinary incontinence as a predominant symptom.

          -  Participant has an average total daily urine volume > 3000 mL (as recorded in a 3-day
             voiding diary period).

          -  Participant has indwelling catheter or practices intermittent self-catheterization.

          -  Participant has neurogenic detrusor overactivity or indicated pathology other than
             OAB.

          -  Participant as monosymptomatic enuresis.

          -  Participant has post void residual (PVR) volume of ≥ 100 mL or a clinically
             significant lower urinary tract obstructive disease, except if successfully treated.

          -  Participant has anatomical anomalies (surgically treated or untreated) that affect
             lower urinary tract function.

          -  Participant with hematuria on dipstick test. In the case of hematuria on dipstick test
             in a female during menstruation, the test can be repeated before randomization (after
             the end of menstruation).

          -  Participant has lower urinary tract stones or clinically significant kidney stones
             requiring treatment.

          -  Participant has interstitial cystitis.

          -  Participant has suffered from chronic urinary tract infection (UTI) or has had more
             than 3 ETIs in the 2 months prior to visit 1/week -1 to -2 (screening).

          -  Participant has uncontrolled hypertension (sitting systolic blood pressure [SBP] ≥ 180
             mmHg or diastolic blood pressure [DBP] ≥ 110 mmHg).

          -  Participant has pulse rate ≥ 110 beats per minute (bpm) or <50 bpm.

          -  Participant has corrected QT interval by Fredericia (QTcF) > 440 msec on screening ECG
             or a risk of QT prolongation (e.g., hypokalemia, long QT syndrome [LQTS] or family
             history of LQTS or exercise-induced syncope).

          -  Participant's aspartate aminotransferase (AST) or alanine aminotransferase (ALT) is ≥
             2 × upper limit of normal (ULN) or total bilirubin (TBL) is ≥ 1.5 × ULN according to
             age and sex (participants with Gilbert's syndrome are excepted from the bilirubin
             threshold).

          -  Participant has moderate or severe renal impairment.

          -  Participant has a symptomatic (symptoms can include pain, fever, hematuria, new onset
             foul-smelling urine) UTI. Note: if the UTI is treated successfully (clinical recovery:
             confirmed by dipstick test and repeated dipstick test after 14 days [both should be
             negative]), the participant can be rescreened.

          -  Participant has a history or presence of any malignancy (previous or current diagnosis
             of bladder or prostate cancer).

          -  Participant uses any drugs that are sensitive cytochrome P450 2D6 (CYP2D6) substrates
             with a narrow therapeutic index or sensitive P-glycoprotein (P-gp) substrates after
             the start of washout.

          -  Participant is using or has used prohibited prior and/or concomitant medication(s). In
             case α1-AR antagonists, 5α-reductase inhibitors (5-ARIs) and Phosphodiesterase type 5
             inhibitors (PED-Is) are used for Benign Prostatic Hyperplasia(BPH), participant can be
             included in the study.

          -  Participant has known or suspected hypersensitivity to mirabegron or any components of
             the formulations used.

          -  Participants previously treated for OAB including medication and nondrug treatment. If
             the treatment stopped for 2 weeks or more prior to the screening visit, participants
             can be included in the study.

          -  Participant has participated in another clinical study (and/or participant has
             received any investigational therapy within 30 days (or 5 half-lives of the drug, or
             the limit set by national law, whichever is longer) prior to visit 1/week -1 to -2
             (screening).

          -  Participant has constipation as defined by the Rome IV criteria that cannot be
             successfully treated prior to study entry.

          -  Female participant who has been pregnant within 6 months prior to screening or
             breastfeeding within 3 months prior to screening.

          -  Participants has a positive serology test for hepatitis A virus (HAV) antibodies
             (immunoglobulin M [IgM]), hepatitis B core (HBc) antibodies, hepatitis B surface
             antigen (HBsAg), hepatitis C virus (HCV) antibodies, antibodies to human
             immunodeficiency virus (HIV) or syphilis at screening.

          -  Participant is an employee of Astellas, the study-related contract research
             organizations (CROs) or the clinical unit.

          -  Participant has any condition which makes the participant unsuitable for study
             participation.

        Additional Exclusion at Visit 2/Week 0 (Baseline)

          -  Participant has stress urinary incontinence as a predominant symptom.

          -  Participant has an average total daily urine volume > 3000 mL (as recorded in a 3-day
             voiding diary period).

          -  Participant has monosymptomatic enuresis confirmed by the bladder e-diary.

          -  Participant suffers from a symptomatic (symptoms can include pain, fever, hematuria,
             new onset foul-smelling urine) UTI. Note: if a symptomatic UTI is present, all visit
             2/week 0 (baseline) assessments must be postponed until the UTI is successfully
             treated (clinical recovery: confirmed by dipstick test and repeated dipstick test
             after 14 days [both should be negative]). The postponed visit 2/week 0 (baseline)
             should be within 14 days of the intended visit 2/week 0 (baseline).

          -  Participant with hematuria on dipstick test. In the case of hematuria on dipstick test
             in a female during menstruation, the test can be repeated before randomization (after
             the end of menstruation).

          -  Participant has uncontrolled hypertension (sitting SBP ≥ 180 mmHg or DBP ≥ 110 mmHg).

          -  Any reason that makes the participant unsuitable for study participation.