A Study With Mirabegron 50 mg and 25 mg in Chinese Participants With Overactive Bladder
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy of mirabegron for the treatment of overactive blsdder (OAB) in Chinese participants. This study will also evaluate the safety of mirabegron for the treatment of OAB in Chinese participants, evaluate other efficacy variables of mirabegron for the treatment of OAB and explore different mirabegron starting doses.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed Description
The study follows an open-label, randomized, 12-week, prospective, interventional postauthorization design for the treatment of OAB in approximately 249 Chinese participants. Each participant will take part in one 12-week treatment period. Treatments will be administered once daily orally after a meal during a 12-week, open-label treatment period. Study visits will take place at weeks 4, 8 and 12. For 25 mg mirabegron group, a dose escalation to 50 mg is permitted on visit 3 and visit 4 at investigators' discretion. Approximately 10 study sites across China are planned.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Mirabegron 25 mg Participants will receive 25 mg of mirabegron, once daily orally in the morning around the same time of day and around time of food intake (i.e., within 1 hour after breakfast). |
Drug: mirabegron
Mirabegron will be administered as single oral dose of 25 mg or 50 mg sustained-release tablet
Other Names:
|
| Experimental: Mirabegron 50 mg Participants will receive 50 mg of mirabegron, once daily orally in the morning around the same time of day and around time of food intake (i.e., within 1 hour after breakfast). |
Drug: mirabegron
Mirabegron will be administered as single oral dose of 25 mg or 50 mg sustained-release tablet
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change from baseline to week 12 in mean number of micturitions per 24 hours [Baseline and week 12]
Participants will complete a 3-day bladder e-diary, at least 3 and not more than 7 days before each visit. Micturition is defined as the passing of urine. The mean number of micturitions per 24 hours will be calculated by taking the sum of all urination episodes documented in the participant diary, divided by the number of valid diary days.
Secondary Outcome Measures
- Change from baseline in mean number of micturitions per 24 hours with either 50 mg or 25 mg dose [Baseline and week 4, week 8]
Participants will complete a 3-day bladder e-diary, at least 3 and not more than 7 days before each visit. Micturition is defined as the passing of urine. The mean number of micturitions per 24 hours will be calculated by taking the sum of all urination episodes documented in the participant diary, divided by the number of valid diary days.
- Frequency of Adverse Events (AE) [Up to 14 weeks]
AEs will be coded using MedDRA. An AE is any untoward medical occurrence in a participant, temporally associated with the use of study investigational product (IP) whether or not considered related to the study IP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study IP. This includes events related to the comparator and events related to the (study) procedures. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect.
- Severity of Adverse Events [Up to 14 weeks]
AEs will be coded using MedDRA. An AE is any untoward medical occurrence in a participant, temporally associated with the use of study investigational product (IP) whether or not considered related to the study IP. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study IP. This includes events related to the comparator and events related to the (study) procedures. An SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect.
- Number of participants with laboratory value abnormalities and/or adverse events (AEs) [Baseline and week 12]
Number of participants with potentially clinically significant laboratory values.
- Number of participants with vital sign abnormalities and/or adverse events (AEs) [Baseline up to week 12]
Number of participants with potentially clinically significant vital sign values.
- Number of participants with electrocardiogram (ECG) abnormalities and/or Adverse Events (AEs) [Baseline and week 12]
Number of participants with potentially clinically significant ECG values.
- Change From Baseline to Week 12 in Post Void Residual (PVR) Volume [Baseline and week 12]
PVR will be measured by ultrasonography.
- Change from baseline in mean number of grade 3 or 4 (PPIUS) urgency episodes per 24 hours with either 50 mg or 25 mg dose [Baseline and week 4, 8, and 12]
Participants will complete a 3-day bladder e-diary, at least 3 and not more than 7 days before each visit. An urgency episode is defined as a complaint of a sudden, compelling desire to pass urine, which is difficult to defer. The mean number of urgency episodes per 24 hours will be calculated by taking the sum of all urgency episodes documented in the participant diary, divided by the number of days of valid diary days.
- Change from baseline in mean number of daytime incontinence episodes per 24 hours with either 50 mg or 25 mg dose [Baseline and week 4, 8, and 12]
Participants will complete a 3-day bladder e-diary, at least 3 and not more than 7 days before each visit. A daytime incontinence episode is defined as the complaint of any involuntary leakage of urine during daytime hours. The mean number of daytime incontinence episodes per 24 hours will be calculated by taking the sum of all daytime urinary incontinence episodes documented in the participant diary, divided by the number of valid diary days.
- Change from baseline in mean number of nighttime incontinence episodes per 24 hours with either 50 mg or 25 mg dose [Baseline and week 4, 8, and 12]
Participants will complete a 3-day bladder e-diary, at least 3 and not more than 7 days before each visit. A nighttime incontinence episode is defined as the complaint of any involuntary leakage of urine during nighttime hours. The mean number of nighttime incontinence episodes per 24 hours will be calculated by taking the sum of all nighttime urinary incontinence episodes documented in the participant diary, divided by the number of valid diary days.
- Change from baseline in mean number of urge incontinence episodes per 24 hours with either 50 mg or 25 mg dose [Baseline and week 4, 8, and 12]
Participants will complete a 3-day bladder e-diary, at least 3 and not more than 7 days before each visit. An urge incontinence episode is defined as any episode when both urgency and incontinence occurred concurrently. The mean number of urge incontinence episodes per 24 hours will be calculated by taking the sum of all urge incontinence episodes documented in the participant diary, divided by the number of valid diary days.
- Change from baseline in OAB Symptom Score (OABSS) with either 50 mg or 25 mg dose [Baseline and week 4, 8, and 12]
The OABSS questionnaire is designed to quantify OAB symptoms as a single score, and contains questions that address 4 symptoms of overactive bladder: Daytime frequency, Nighttime frequency, Urgency, and Urge incontinence. The OABSS has a maximum score of 15 with more weight assigned to urgency and urgency incontinence than on frequency. The OABSS total score will be calculated from the sum total of the score of each question. The total score ranges from 0 to 15 with higher score indicating more symptoms.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Subject should exhibit symptoms of OAB for at least 12 weeks before initiation of the screening period.
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Subject should have an average of ≥ 8 micturitions/24 hours.
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Subject 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.
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Female subject is not pregnant and at least one of the following conditions apply:
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Not a woman of childbearing potential (WOCBP)
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WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 30 days after final IP administration.
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Female subject must agree not to breastfeed starting at screening and throughout the study period and for 30 days after final IP administration.
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Female subject 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.
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Male subject 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.
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Male subject must not donate sperm during the treatment period and for 30 days after final IP administration.
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Male subject 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.
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Subject 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)
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Subject has stress urinary incontinence as a predominant symptom.
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Subject has an average total daily urine volume > 3000 mL (as recorded in a 3-day voiding diary period).
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Subject has indwelling catheter or practices intermittent self-catheterization.
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Subject has neurogenic detrusor overactivity or indicated pathology other than OAB.
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Subject as monosymptomatic enuresis.
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Subject has post void residual (PVR) volume of ≥ 100 mL or a clinically significant lower urinary tract obstructive disease, except if successfully treated.
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Subject has anatomical anomalies (surgically treated or untreated) that affect lower urinary tract function.
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Subject 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).
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Subject has lower urinary tract stones or clinically significant kidney stones requiring treatment.
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Subject has interstitial cystitis.
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Subject has suffered from chronic UTI or has had more than 3 ETIs in the 2 months prior to visit 1/week -1 to -2 (screening).
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Subject has uncontrolled hypertension (sitting systolic blood pressure [SBP] ≥ 180 mmHg or diastolic blood pressure [DBP] ≥ 110 mmHg).
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Subject has pulse rate ≥ 110 beats per minute (bpm) or <50 bpm.
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Subject 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).
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Subject'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 (subjects with Gilbert's syndrome are excepted from the bilirubin threshold).
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Subject has moderate or severe renal impairment.
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Subject 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 subject can be rescreened.
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Subject has a history or presence of any malignancy (previous or current diagnosis of bladder or prostate cancer).
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Subject 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.
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Subject 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), Subject can be included in the study.
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Subject has known or suspected hypersensitivity to mirabegron or any components of the formulations used.
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Subjects previously treated for OAB including medication and nondrug treatment. If the treatment stopped for 2 weeks or more prior to the screening visit, Subjects can be included in the study.
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Subject has participated in another clinical study (and/or subject 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).
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Subject has constipation as defined by the Rome IV criteria that cannot be successfully treated prior to study entry.
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Female subject who has been pregnant within 6 months prior to screening or breastfeeding within 3 months prior to screening.
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Subjects 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.
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Subject is an employee of Astellas, the study-related contract research organizations (CROs) or the clinical unit.
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Subject has any condition which makes the subject unsuitable for study participation.
Additional Exclusion at Visit 2/Week 0 (Baseline)
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Subject has stress urinary incontinence as a predominant symptom.
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Subject has an average total daily urine volume > 3000 mL (as recorded in a 3-day voiding diary period).
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Subject has monosymptomatic enuresis confirmed by the bladder e-diary.
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Subject 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).
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Subject 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).
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Subject has uncontrolled hypertension (sitting SBP ≥ 180 mmHg or DBP ≥ 110 mmHg).
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Any reason that makes the subject unsuitable for study participation.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Site CN86020 | Wuhan | Hubei | China | |
| 2 | Site CN86001 | Beijing | China | ||
| 3 | Site CN86004 | Beijing | China | ||
| 4 | Site CN86014 | Beijing | China | ||
| 5 | Site CN86010 | Chengdu | China | ||
| 6 | Site CN86009 | Guangzhou | China | ||
| 7 | Site CN86018 | Guangzhou | China | ||
| 8 | Site CN86003 | Lanzhou | China | ||
| 9 | Site CN86013 | Shanghai | China | ||
| 10 | Site CN86002 | Suzhou | China | ||
| 11 | Site CN86021 | Taiyuan | China | ||
| 12 | Site CN86011 | Wuhan | China | ||
| 13 | Site CN86022 | Wuxi | China | ||
| 14 | Site CN86012 | Xi'an | China | ||
| 15 | Site CN86007 | Zhengzhou | China |
Sponsors and Collaborators
- Astellas Pharma China, Inc.
Investigators
- Study Director: Executive Director, Astellas Pharma China, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 178-MA-2295
- CTR20202160