A Randomized, Double-Blind, Multi-Centre Study to Evaluate the Efficacy and Safety of Adding Mirabegron to Solifenacin in Incontinent OAB Subjects who have Received Solifenacin for 4 Weeks and Warrant Additional Relief for their OAB Symptoms.
- Conditions
- Overactive bladderincontinence10004994
- Registration Number
- NL-OMON38806
- Lead Sponsor
- Astellas Pharma B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 40
Inclusion At screening Visit (visit 1):
1. Subject is male or female and at least 18 years of age;
2. Subject has symptoms of OAB (urinary frequency and urgency with urgency incontinence)
for >= 3 months prior to the screening visit
3. Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)-approved written Informed Consent (IC) and privacy language as per national regulations has been obtained from the subject prior to any study-related procedures (including discontinuation of prohibited medication, if applicable);
4. Female subject must be either:
• Of non child bearing potential:
- post-menopausal (defined as at least 1 year without any menses in the absence of other plausible aetiology) prior to Screening or
- documented surgically sterile or status post hysterectomy (at least 1 month prior to Screening)
• Or, if of childbearing potential,
-must have a negative serum pregnancy test at Screening and must use a highly effective method of birth control, which include established use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), or barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository. Birth control must be practiced from the Screening visit, throughout the study period and for 28 days after final study drug administration;
5. Female subject must not be breastfeeding at Screening or during the study period and for 28 days after final study drug administration;
6. Female subject must not donate ova starting at Screening and throughout the study period and for 28 days after final study drug administration;
7. Male subjects and their female spouse/partners who are of childbearing potential must be using highly effective contraception (see criteria 4 above) starting at Screening and continue throughout the study period and for 90 days after final study drug administration;
8. Male subject must not donate sperm starting at Screening and throughout the study period and for at least 90 days after final study drug administration;
9. Subject is willing and able to complete the micturition diary and questionnaires correctly, including collection and measurement of urine output for 3 days prior to each visit;
10. Subject has symptoms of *wet* OAB (urinary frequency and urgency with incontinence or mixed incontinence with predominant urgency incontinence), and reports an average of at least 2 incontinence episodes per 24 hour period. ;At run-in (visit 2):
11. Subject experiences on average at least 1 episode of urgency (grade 3 or 4) with or without incontinence per 24-hour period during the 3-day micturition diary period.
12. Subject experiences on average at least 2 incontinence episodes per 24-hour period during the 3-day micturition diary period.
13. Subject experiences on average at least 8 micturitions (excluding incontinence episodes) per 24-hour period during the 3-day micturition diary period. ;At randomization (visit 3):
14. Subject experiences at least 1 incontinence episode during the 3-day micturition diary period and wishes to increase their treatment for OAB symptoms.
Subjects will be excluded from participation if any of the following apply:
At screening (visit 1):
1. Subject in the opinion of the investigator has clinically significant Bladder Outlet Obstruction (BOO).
2. Subject has significant PVR volume (PVR > 150 ml).
3.Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the investigator
4. Subject has an indwelling catheter or practices intermittent self-catheterization.
5.Subject has evidence of a Urinary Tract Infection (UTI). If a urine dipstick shows positive for nitrite, this must be followed up with a urine sediment and then culture (if the sediment is positive). The subject should be treated with an appropriate course of antibiotics. The subject can be enrolled into the study after successful treatment of the UTI, which is confirmed by a dipstick test negative for nitrites. If more than 28 days has passed since the initial screening visit, the subject must repeat the screening assesments.
6.Subject has chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy, or previous or current malignant disease of the pelvic organs (i.e., within the confines of the pelvis including the bladder and rectum in both sexes, the prostate in males and the uterus, ovaries, and fallopian tubes in females; organs of the lower gastrointestinal tract are not necessarily considered pelvic organs as the distal ascending colon, the full transverse colon and proximal portion of the descending colon are in the abdomen).
7. Subject has received intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin;
8. Subject has uncontrolled narrow angle glaucoma, urinary or gastric retention, severe ulcerative colitis, toxic megacolon, myasthenia gravis or any other medical condition which in the opinion of the investigator makes the use of anticholinergics contraindicated.
9. Subject receives non-drug treatment including sacral nerve stimulation therapy (a bladder training program or pelvic floor exercises which started more than 30 days prior to entry into the study can be continued).
10. Subject has moderate to severe hepatic impairment defined as Child Pugh Class B or C.
11. Subject has severe renal impairment or End Stage Renal disease defined as eGFR < 30 ml/min/1.73 m2.
12. Subject has serum creatinine > 150 µmol/L, AST and/or ALT > 2x upper limit of normal (ULN), γ-GT > 3x ULN, or total bilirubin 2x ULN, as assessed in screening samples.
13. Subject has severe uncontrolled hypertension, which is defined as a sitting average systolic blood pressure >= 180 mmHg and/or average diastolic blood pressure >= 110 mmHg.
14. Subject has a QTcF interval > 450 ms for males or > 470 ms for females or is at risk of QT prolongation (e.g., family history of long QT syndrome, hypokalaemia);
15. Subject has a clinically significant abnormal ECG;
16. Subject has a known or suspected hypersensitivity to solifenacin, mirabegron or any of the inactive ingredients. This includes subjects with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorbtion.
17. Subject has any other clinically significant condition, which in the opinion of the investigator makes the subject unsuitable for the study.
18. Subject has been treated with an exper
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary time point comparison for all variables is from Baseline Visit<br /><br>(Visit 3/Randomization) to End of Treatment (Visit 6).<br /><br><br /><br>Primary variable:<br /><br>Change from Baseline in mean number of incontinence episodes </p><br>
- Secondary Outcome Measures
Name Time Method