A study in patients with overactive bladder to evaluate the efficacy,safety and tolerability of a combination of two drugs (solifenacinsuccinate and mirabegron) with either drug alone, and to find the bestdose for each of the drugs in combinatio
- Conditions
- Overactive bladderMedDRA version: 13.1Level: LLTClassification code 10059617Term: Overactive bladderSystem Organ Class: 10038359 - Renal and urinary disordersTherapeutic area: Body processes [G] - Physical Phenomena [G01]
- Registration Number
- EUCTR2010-020601-32-NO
- Lead Sponsor
- Astellas Pharma Europe BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 1658
Inclusion Criteria at Visit 1/Screening
1.Subject is male or female and at least 18 years of age;
2.Subject has a Body Mass Index (BMI) of between 18 and 35 kg/m2 and a total body weight between 50 and 95 kg;
3.Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent 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. Subject is willing and able to complete the micturition diary and questionnaires correctly and is willing and able to measure his/her vital signs at home at stipulated time points, using the device provided by the study personnel, and to adequately record the readings
5. Subject has symptoms of OAB (urinary frequency, urgency and/or urgency incontinence) for at least 3 months
Inclusion Criteria at Visit 2/Placebo Run-In
6. Subject must still fulfill all inclusion criteria and none of the exclusion criteria for Visit 1;
7. Subject is willing and able to complete the micturition diary correctly and is willing and able to measure his/her vital signs at home at stipulated time points, using the device provided by the study personnel, and to adequately record the readings
Inclusion Criteria at Visit 3/Baseline
8. Subject continues to meet all inclusion criteria and none of the exclusion criteria for Visit 1;
9. Subject has experienced frequency of micturition on average = 8 times per 24-hour period during the 3-day micturition diary period (incontinence episode should not be counted as a micturition);
10. Subject must experience at least 1 episode of urgency (grade 3 or 4) per 24-hour period (with or without urgency incontinence) during the 3 day micturition diary period.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1045
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 613
Exclusion Criteria at Visit 1/Screening
1. Subject is breastfeeding, pregnant or intends to become pregnant during the study. The pregnancy test (ß-HCG in serum) at Screening must be negative in women of childbearing potential;
2. Female subjects of childbearing potential and not using a highly effective method of birth control during the study and for 30 days after final study drug administration.
3. Male subjects (unless surgically sterile) with female spouses/partners who are of childbearing potential, and not using a barrier method of contraception during the study and for 30 days after final study drug administration. In addition, female spouses/partners of male subjects and who are of childbearing potential should also use a highly effective method of birth control during the study and for 30 days after final study drug administration. Highly effective methods of birth control are defined as those, alone or in combination, that result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly.
4. In the opinion of the Investigator, the subject has clinically significant bladder outflow obstruction at risk of urinary retention;
5. Subject has significant PVR volume (> 150 mL);
6. Subject has significant stress incontinence or mixed stress/urgency incontinence where stress is the predominant factor as determined by the Investigator (for female subjects confirmed by the cough provocation test
7. Subject has a neurological cause for detrusor overactivity;
8. Subject has an indwelling catheter or practices intermittent self-catheterization;
9. Subject has diabetic neuropathy;
10. Subject has chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs;
11. Subject has had previous lower urinary tract or pelvic floor surgery (except cystoscopy);
12. Subject has had intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin;
13. Subject has uncontrolled narrow angle glaucoma, urinary or gastric retention, severe ulcerative colitis or Crohn’s Disease, toxic megacolon, myasthenia gravis or any other condition which makes the use of anticholinergics contraindicated;
14. Subject has clinically significant cardiovascular or cerebrovascular diseases within 6 months prior to Screening, such as myocardial infarction, uncontrolled angina, significant ventricular arrhythmias, heart failure and stroke;
15. Subject is receiving current non-drug treatment including electro-stimulation therapy (with the exception of a bladder training program or pelvic floor exercises which started more than 30 days prior to Screening);
16. Subject is using medications intended to treat OAB or prohibited medications. Subject is excluded if using restricted medications under conditions different to those specified in the Concomitant Medication” section;
17. Subject has known or suspected hypersensitivity to solifenacin succinate, mirabegron or any of their excipients;
18. Subject has any significant neurological disease or defect affecting bladder function (e.g., neurogenic bladder, systemic or central neurological disease such as multiple sclerosis [MS] and Parkinson’s disease);
19. Subject has severe hypertension which is defined as a sitting average systolic blood pressure = 180 mmHg and/or an average diastolic blood pressure = 110 mmHg;
20. Subject has any clinically sig
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of four combinations of solifenacin succinate (2.5 mg or 5 mg) plus mirabegron (25 mg or 50 mg) vs. solifenacin succinate 5 mg monotherapy<br>;Secondary Objective: To investigate the dose-response surface of combinations of solifenacin succinate (0 mg, 2.5 mg, 5 mg and 10 mg) and mirabegron (0 mg, 25 mg and 50 mg) doses;<br><br>To compare the safety and tolerability of six combinations of solifenacin succinate and mirabegron vs. solifenacin succinate monotherapy, mirabegron monotherapy, and placebo;<br><br>To investigate the population pharmacokinetics (PK) and PK/pharmacodynamic (PD) relationship of six combinations of solifenacin succinate and mirabegron and the mirabegron and solifenacin succinate monotherapies.<br>;Primary end point(s): Change from baseline in mean volume voided per micturition after 12 weeks of treatment <br><br>;Timepoint(s) of evaluation of this end point: After 12 weeks of treatment
- Secondary Outcome Measures
Name Time Method Secondary end point(s): Change from baseline in mean number of micturitions/24 h<br>Change from baseline in mean number of incontinence episodes/24 h;Timepoint(s) of evaluation of this end point: Every 24 hours