Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized, Double-Blind, Factorial, Parallel-Group, Active and Placebo-Controlled, Multicenter Dose-Ranging Study to Evaluate the Efficacy, Safety and Tolerability of Six Dose Combinations of Solifenacin Succinate and Mirabegron Compared to Mirabegron and Solifenacin Succinate Monotherapies in the Treatment of Overactive Bladder.
Brief Summary: The purpose of this study is to examine how well two medicines in combination (solifenacin succinate and mirabegron) work in the treatment of bladder problems over a 12-week period.


Options:
A: Inclusion Criteria:

* At least 1 urinary urgency episode/24h (on average) documented in a 3-day patient diary in the screening phase with or without urge incontinence, and usually with frequency and nocturia, described as OAB
* Patients may be included if they were never exposed to anticholinergic agents specified for the treatment of OAB. Patients may also be included if they have previously been treated with FDA-approved anticholinergic agents for the treatment of OAB such as oxybutynin chloride and are no longer receiving such treatment for a minimum of 14 days immediately preceding entry into the study. These previously treated patients must present at the investigative site on no anticholinergic agents and with the desire to receive treatment for OAB. Previous non-drug treatment of OAB is allowed if it has been established at least 4 weeks prior to study entry and is continued throughout the study.
* Patients having urgency with or without urge incontinence accompanied by frequency of ≥8 episodes per 24 hours, and/or nocturia, for a period of ≥3 months prior to screening.

Exclusion Criteria:

* Previous treatment with darifenacin
* Duration of urgency with or without urge incontinence, usually accompanied with frequency and nocturia for \<3 months
* Significant stress incontinence or mixed stress/urge incontinence where stress is the predominant factor as determined by the Investigator
* Evidence of a urinary tract infection; chronic inflammation such as interstitial cystitis and bladder stones
* Clinically significant outflow obstruction (benign prostatic hyperplasia) as determined by the Investigator
B: Inclusion Criteria:

* Ambulatory and able to use the toilet without difficulty
* History of OAB symptoms for ≥ 3 months
* An average of ≥ 8 micturitions per 24 hours and ≥ 1 urgency episode (with or without incontinence) per 24 hours as documented in a 3-day micturition diary
* Subjects are bothered by symptoms as reflected by OAB-questionnaire

Exclusion Criteria:

* Patient has stress or mixed incontinence
* Patient has Benign Prostatic Hyperplasia with severe lower urinary tract symptoms based on IPSS score
* Patient has uncontrolled Diabetes Mellitus Type II Patient has Diabetes Insipidus, UTI
* Patient has history of interstitial cystitis, painful bladder syndrome, or chronic pelvic pain
* Patient has a history of stroke, seizures, or major neurological disorders
* Patient has a history of fecal incontinence and or continual urine leakage
* Patient has had surgery to correct stress urinary incontinence or pelvic organ prolapse within 6 months of study start
* Patient received bladder training of electrostimulation within 2 weeks of study start
* Patient requires a catheter
* Patient is taking medications that cannot be stopped for the duration of the trial including certain anticholinergics or smooth muscle relaxants
* Patient began taking tricyclic antidepressants, serotonin/norepinephrine reuptake inhibitors, calcium channel blockers, ephedrine/pseudoephedrine, or diuretic therapy less than 8 weeks before study start
* Patient has been on hormone replacement therapy for less than 12 weeks at study start
* Patient must take medication for arrhythmia, contraindicated for Solifenacin or Gabapentin
* Patient has multiple and/or severe allergies to foods and drugs
* Patient regularly uses any illegal drugs
C: Inclusion Criteria:

* Overactive Bladder Syndrome

Exclusion Criteria:

* less than 8 micturitions in 24 hours
D: Inclusion Criteria:

* Inclusion Criteria at Visit 1/Screening:

  * Subject has a Body Mass Index (BMI) of between 18 and 35 kg/m\^2 and a total body weight between 50 and 95 kg;
  * 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;
  * Subject has symptoms of overactive bladder (OAB; urinary frequency, urgency and/or urgency incontinence) for at least 3 months.
* Inclusion Criteria at Visit 3/Baseline:

  * 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);
  * 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.

Exclusion Criteria:

* Exclusion Criteria at Visit 1/Screening:

  * Subject is breastfeeding, pregnant or intends to become pregnant during the study. The pregnancy test (Beta Human Chorionic Gonadotropin in serum) at Screening must be negative in women of childbearing potential;
  * 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.
  * 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.
  * Subject has significant post-void residual (PVR) volume (\> 150 mL);
  * 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);
  * Subject has a neurological cause for detrusor overactivity;
  * Subject has an indwelling catheter or practices intermittent self-catheterization;
  * Subject has diabetic neuropathy;
  * Subject has chronic inflammation such as interstitial cystitis, bladder stones, previous pelvic radiation therapy or previous or current malignant disease of the pelvic organs;
  * Subject has had previous lower urinary tract or pelvic floor surgery (except cystoscopy);
  * Subject has had intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin;
  * 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;
  * 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;
  * 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);
  * Subject is using medications intended to treat OAB or prohibited medications.
  * Subject has known or suspected hypersensitivity to solifenacin succinate, mirabegron or any of their excipients;
  * 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);
  * 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;
* Exclusion Criteria at Visit 2/Placebo Run-In:

  * Subject has evidence of a urinary tract infection (UTI) (urine culture containing \> 100,000 cfu/mL). The subject can be enrolled into the study after successful treatment of the UTI (confirmed by a laboratory result of negative urine culture). However, the subject must be re screened if the initial screening visit was \> 28 days;
  * Subject has a QT interval \> 450 ms or is at risk of QT prolongation (e.g., family history of long QT syndrome, hypokalaemia) or is on drug treatment known to be associated with QT prolongation;
  * Subject has clinically significant abnormalities on the 12 lead electrocardiogram (ECG);
  * Subject has serum creatinine \> 150 µmol/L, aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 2x upper limit of normal (ULN), gamma-glutamyltransferase (γ-GT) \> 3x ULN, or total bilirubin \> 2x ULN, as assessed in Screening samples;
* Exclusion Criteria at Visit 3/Baseline:

  * Subject had an average total daily urine volume \> 3000 mL as recorded in the micturition diary period;
  * 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.

Answer: D