Clinical trial NCT04562090: A Study With Mirabegron 50 mg and 25 mg in Chinese Participants With Overactive Bladder
Official title: A Phase 4, Open-label, Randomized, Prospective, Interventional Post-authorization Efficacy and Safety Study of Mirabegron 50 mg and 25 mg for the Treatment of Overactive Bladder in Chinese Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Urge Incontinence
Overactive Bladder (OAB)
Keywords: mirabegron
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2020-09-24
Enrollment: 249
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

Brief 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.

Detailed description: The study followed an open-label, randomized, 12-week, prospective, interventional post-authorization design for the treatment of OAB in 249 Chinese participants. Each eligible participant took part in a 12-week treatment period. Treatments were administered once daily orally after a meal during a 12-week, open-label treatment period. Study visits took place at weeks 4, 8 and 12. For the 25 mg mirabegron group, a dose escalation to 50 mg was permitted on visit 3 and visit 4 at the investigators' discretion. 15 study sites across China enrolled participants.

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.

Primary outcomes:
measure: Change From Baseline (CFB) to the End of 12-Week Treatment Period in Mean Number of Micturition/24 Hours in Mirabegron 50 mg Group
timeFrame: Baseline, week 12
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events
timeFrame: From first dose up to 30 days after last dose (up to week 16)
measure: Change From Baseline to Week 12 in Post Void Residual (PVR) Volume
timeFrame: Baseline, week 12
measure: Change From Baseline in Mean Number of Grade 3 or 4 Patient Perception of Intensity of Urgency Scale (PPIUS) Urgency Episodes Per 24 Hours
timeFrame: Baseline and weeks 4, 8, and 12
measure: Change From Baseline in Mean Number of Daytime Incontinence Episodes Per 24 Hours
timeFrame: Baseline and weeks 4, 8, and 12
measure: Change From Baseline in Mean Number of Nighttime Incontinence Episodes Per 24 Hours
timeFrame: Baseline and weeks 4, 8, and 12
measure: Change From Baseline in Mean Number of Urge Incontinence Episodes Per 24 Hours
timeFrame: Baseline and weeks 4, 8, and 12
measure: Change From Baseline in OAB Symptom Score (OABSS)
timeFrame: Baseline and weeks 4, 8, and 12
measure: Change From Baseline in Mean Number of Micturition Per 24 Hours
timeFrame: Baseline and weeks 4 and 8
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Site CN86020
state: Hubei
city: Beijing
country: China
facility: Site CN86001
city: Beijing
country: China
facility: Site CN86004
city: Beijing
country: China
facility: Site CN86014
city: Chengdu
country: China
facility: Site CN86010
city: Guangzhou
country: China
facility: Site CN86009
city: Guangzhou
country: China
facility: Site CN86018
city: Lanzhou
country: China
facility: Site CN86003
city: Shanghai
country: China
facility: Site CN86013
city: Suzhou
country: China
facility: Site CN86002
city: Taiyuan
country: China
facility: Site CN86021
city: Wuhan
country: China
facility: Site CN86011
city: Wuxi
country: China
facility: Site CN86022
city: Xi'an
country: China
facility: Site CN86012
city: Zhengzhou
country: China
facility: Site CN86007
Study officials:
affiliation: Astellas Pharma China, Inc.
name: Executive Director
role: STUDY_DIRECTOR
References: