A Study With Mirabegron 50 mg and 25 mg in Chinese Participants With Overactive Bladder

Launched by ASTELLAS PHARMA CHINA, INC. · Sep 18, 2020

Keywords

ClinConnect Summary

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.

Gender

ALL

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.