Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Study to Evaluate the Overall Effect of Solifenacin 5mg and 10mg on Bladder Wall Thickness and Urinary Nerve Growth Factor in Female Subjects With Overactive Bladder and a Diagnosis of Detrusor Overactivity - A Double-blind, Randomised, Placebo-controlled, Parallel Group, Multi-centre Study.
Brief Summary: The purpose is to see if solifenacin has any effect on bladder wall thickness and urine inflammatory marker measurements after 12 weeks of treatment.


Options:
A: Inclusion Criteria:

* Ambulatory females ≥ 18 years old
* Urge Urinary Incontinence (subject-reported) for ≥ 3 months prior to Screening (Visit 1)
* On the 3IQ: Response b to Question 3: During the last 3 months, did you leak urine most often: b. When you had the urge or the feeling that you needed to empty your bladder, but could not get to the toilet fast enough?
* On a 3-day bladder diary, documentation of an average of 1 UUI episode per 24 hours (3 UUI episodes in 3 days)
* Capability of understanding and having signed the informed consent form after full discussion of the research nature of the treatment and its risk and benefits
* Ability to perform all procedures and tests required by the protocol
* Willingness to remain on stable medication regime for duration of the randomized controlled trial. Participants will be asked to not add new medications during the randomized controlled trial, such as diuretics and other medications which may affect their voiding pattern.

Exclusion Criteria:

* Any condition that would contraindicate their usage of fesoterodine including: hypersensitivity to the active drug (fesoterodine fumarate) and its ingredients or any of the excipients, history of urinary retention, gastric retention, uncontrolled narrow angle glaucoma, myasthenia gravis, severe hepatic impairment (Child Pugh C), severe ulcerative colitis, toxic megacolon, fistula or a hole in your bladder or rectum, birth defect leading to urine leakage, and urine leakage starting in childhood.
* Clinically significant hepatic or renal disease.
* Neurologic conditions such as stroke, multiple sclerosis, spinal cord injury, or Parkinson's disease.
* Symptomatic pelvic organ prolapse defined as participant report of feeling or seeing a bulge outside the vagina within the past 3 months.
* History of lower urinary tract/pelvic surgery (e.g. surgery for incontinence in the past 5 years, surgery in the past 6 months for prolapse or hysterectomy), intra-vesical therapy (botox), and/or bulk injections within the past 6 months.
* A known history of interstitial cystitis or a significant pain component associated with OAB symptoms, uninvestigated hematuria, urogenital cancer, interstitial or external radiation to the pelvis or external genitalia.
* Urinary tract infection (UTI) as shown by the results of the urinalysis at screening or recurrent urinary tract infection (RUTIs) defined as treatment for UTI \>3 times in the last year.
* Use of any electrostimulation, bladder training, or pelvic floor exercises (with certified incontinence practitioners) within 4 weeks of Screening.
* Received study medication in any previous fesoterodine clinical trial.
* Prior failure for either efficacy or tolerability of ≥ 2 OAB medications in the last year. (failure: inadequate symptom control after two medications for a minimum of one month each)
* Has been treated within 2 weeks prior to Screening and/or is currently being treated with: - Any drug treatment for overactive bladder, including antimuscarinic OAB medications.
* Any drugs with significant anticholinergic and antispasmodic effects (see exception for tricyclic antidepressants below)
* Has started treatment with tricyclic antidepressants or estrogens within 4 weeks prior to Screening and/or is not on a stable dose.
* Intermittent or unstable use of diuretics. Treatment with diuretics initiated within 2 weeks prior to baseline is not permitted.
* Treatment with potent CYP3A4 inhibitors, such as clarithromycin, ketoconazole, and itraconazole within 2 weeks prior to Screening.
* Administration of medications capable of inducing hepatic enzyme metabolism or transport (e.g., barbiturates, rifampicin, carbamazepine, phenytoin, primidone, or St. John's Wort) in the past 30 days.
* Previously received any investigational drug within 30 days prior to trial entry.
* Alcohol and/or any other drug abuse in the opinion of the investigator.
* Participants who are pregnant, nursing, or with a positive urine pregnancy test or who are intending to become pregnant within 3 months after the completion of the trial.
* Participants that have been pregnant (\> 20 weeks gestation) in the previous 6 months.
* Participants of childbearing potential who are heterosexually active but unwilling or unable to use an adequate form of contraception to prevent pregnancy during the study. Reliable contraceptive methods may include intrauterine devices (IUD), contraceptive pills of combination type, hormonal implants, injectable contraceptives or latex condoms with a spermicide.
* Participants who have any medical (including known history of major hematological, renal, cardiovascular, or hepatic abnormalities) or psychological condition or social circumstances that would impair their ability to participate reliably in the trial, or those who may increase the risk to themselves or others by participating.
* Participants who, in the opinion of the investigator, are not likely to complete the trial for whatever reason.
B: Inclusion Criteria:

* Symptoms of overactive bladder (OAB), including urinary frequency, urgency or urge incontinence, for greater than or equal to 3 months
* Urodynamic diagnosis of detrusor overactivity (DO)
* Either naïve to anti-muscarinic treatment (i.e. no prior history of use of anti-muscarinic agents) or 6-months anti-muscarinic treatment free (i.e. have had no anti-muscarinic treatment within 6 months) prior to the screening visit
* Bladder post-void residual volume of less than 30 ml
* Available to complete the study

Exclusion Criteria:

* History of stress urinary incontinence, urethral sphincter incompetence or neurogenic detrusor overactivity
* History, signs or symptoms suggestive of urinary tract infection (confirmed by positive urine analysis), obstruction or urogenital pro-lapse (greater than grade II)
* History of urinary tract operation within 6 months prior to screening
* Indwelling catheter or permanent catheter fitted
* History of pelvic area radiotherapy treatment
* Uncontrolled diabetes mellitus
* History of fibromyalgia
* Post-partum or breast-feeding within 3 months prior to screening visit
* Either pregnant or intends to become pregnant during the study or sexually active, of childbearing potential and is unwilling to utilize a reliable method of birth control (note: reliable methods are contraceptive pills of combination type, hormonal implants or injectable contraceptives)
* Positive pre-study hepatitis B surface antigen, hepatitis C antibody or human immunodeficiency virus (HIV) result at time of screening
* History of drug and / or alcohol abuse at time of screening
* History of urinary retention, severe gastrointestinal obstruction (including paralytic ileus or intestinal atony or toxic megacolon or severe ulcerative colitis), myasthenia gravis, uncontrolled narrow angle glaucoma or shallow anterior chamber or deemed to be at risk for these conditions
* Undergoing hemodialysis or has severe renal impairment or moderate hepatic impairment or who are on treatment with a potent cytochrome p450 (CYP) 3A4 inhibitor, e.g. Ketoconazole
* Currently dosing with medication(s) intended to treat overactive bladder symptoms or has a history of non-drug treatment, such as electrical therapy, magnetic field stimulation, pelvic floor treatment or bladder training intended to treat overactive bladder symptoms within 6 months prior to screening, as described in the list of prohibited medications
* Currently receiving or has a history of treatment with alpha blockers, botulinum toxin (cosmetic use is acceptable), resiniferatoxin or pelvic floor muscle relaxants within 9 months prior to screening
* Participated in any clinical study less than or equal to 3 months prior to screening
C: Inclusion Criteria:

* The subject has mild cognitive impairment as determined by mini-mental state examination (MMSE) ≥ grade 24
* The subject conforms to the Stockholm criteria for mild cognitive impairment as assessed by the investigator
* The subject has a body mass index (BMI) between 18.0 to 30.0 kg/m2 inclusive
* The subject is available to complete the study

Exclusion Criteria:

* The subject has moderate or severe cognitive impairment as determined by MMSE criteria at screening, ≤ grade 23
* The subject has depression as determined by Geriatric Depression Scale (GDS) short form ≥ 5 at screening
* The subject has a history of urinary retention, severe gastrointestinal obstruction (including paralytic ileus or intestinal atony or toxic megacolon or severe ulcerative colitis), myasthenia gravis, uncontrolled narrow angle glaucoma or shallow anterior chamber or deemed to be at risk for these conditions
* The subject is undergoing hemodialysis or has severe renal impairment or moderate hepatic impairment and who are on treatment with a potent CYP3A4 inhibitor, e.g. Ketoconazole
* The subject has uncontrolled diabetes mellitus
* The subject has a positive pre-study hepatitis B surface antigen, hepatitis C antibody or HIV result at time of screening
* The subject has a history of drug and / or alcohol abuse at time of screening
* The subject has an average weekly alcohol intake of greater than 21 units (male) or 14 units (female) within ≤ 3 months prior to screening (1 unit is 270cc of beer, 40cc of spirits or 125cc of wine)
* The subject has a history of smoking more than 10 cigarettes (or the equivalent amount of tobacco) per day within ≤ 3 months prior to screening
* The subject has a history of known or suspected hypersensitivity to solifenacin succinate, oxybutynin hydrochloride, other anti-cholinergics or lactose, to any component of the dosage form
* The subject has taken any unstable doses of prescribed medication within ≤ 1 month prior to screening or over-the-counter medicine (including vitamins and herbal remedies) within 48 hours prior to the first study day, which in the opinion of the Investigator, will interfere with the study procedures or compromise safety
* The subject is currently dosing with medication(s) intended to treat overactive bladder symptoms or has history of non-drug treatment intended to treat overactive bladder symptoms within ≤ 3 months prior to screening
* The subject has any clinically significant abnormality following Investigator review of the physical examination
* The subject has any clinically significant abnormality following the Investigator's review of the ECG
* The subject has mobility impairment that precludes the assessment of postural stability
* The subject has any clinically significant abnormal heart rate or blood pressure measurements, at the screening visit (dBP \> 90mmHg, sBP \> 160mmHg or HR \< 40bpm or \> 100bpm)
* The subject has any clinically significant abnormality following Investigator's review of the biochemistry \& hematology results which, in the opinion of the Investigator, contraindicates their participation
* The subject has donated blood or plasma within ≤ 3 months prior to screening or more than 500ml or 1 unit of blood or plasma within ≤ 6 months prior to screening
* The subject, may find it difficult to adhere to the provisions of treatment and observation specified in the protocol
* The subject has participated in any clinical study within ≤ 3 months prior to screening
* The subject has any clinical condition, diagnosis, symptomatology or ongoing investigation, which, contraindicates their participation
* The subject is an employee of Astellas Pharma, Cognitive Drug Research, and any other third party related to the study site
D: Inclusion Criteria:

* Subject was willing and able to complete the micturition diary and questionnaires correctly 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 had symptoms of "wet" OAB (urinary frequency and urgency with incontinence) for at least 3 months;

Exclusion Criteria:

* Subject had significant PVR volume (\> 150 mL);
* Subject had a neurological cause for detrusor overactivity (e.g. neurogenic bladder, diabetic neuropathy with autonomic component or bladder involvement, or systemic or central neurological disease such as multiple sclerosis and Parkinson's disease with autonomic component or bladder involvement). An autonomic component could be inferred when autonomic functions were affected, including heart rate, blood pressure, perspiration and digestion.
* Subject had an indwelling catheter or practices intermittent self catheterization.
* Subject had chronic inflammation such as bladder pain syndrome /interstitial cystitis, symptomatic bladder stones or any previous or current radiation cystitis.
* Subject had received intravesical treatment in the past 12 months with e.g., botulinum toxin, resiniferatoxin, capsaicin.
* Subject had moderate to severe hepatic impairment
* Subject had severe renal impairment
* Subject had a clinically significant abnormal ECG
* Subject had a concurrent malignancy or history of cancer (except noninvasive skin cancer) within the last 5 years prior to screening.
* Subject had an average QTcF interval \> 450 ms for males or \> 470 ms for females based on the triplicate ECGs completed at Screening or is at risk of QT prolongation (e.g., family history of long QT syndrome, hypokalaemia).
* Subject had severe hypertension, which is defined as a sitting average systolic blood pressure ≥ 180 mmHg and/or average diastolic blood pressure ≥ 110 mmHg.

Answer: B