A 24-WEEK RANDOMIZED, OPEN-LABEL STUDY TO EVALUATE THE SAFETY AND EFFICACY OF FESOTERODINE IN SUBJECTS AGED 6 TO 17 YEARS WITH SYMPTOMS OF DETRUSOR OVERACTIVITY ASSOCIATED WITH A NEUROLOGICAL CONDITION (NEUROGENIC DETRUSOR OVERACTIVITY)

INTERVENTION: Trade Name: Toviaz Pharmaceutical Form: Prolonged‐release tablet INN or Proposed INN: Fesoterodine Fumarate CAS Number: 286930‐03‐8 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 4‐ Trade Name: Toviaz Pharmaceutical Form: Prolonged‐release tablet INN or Proposed INN: Fesoterodine Fumarate CAS Number: 286930‐03‐8 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 8‐ Trade Name: Lyrinel XL Product Code: Oxybutynin hydrochloride Pharmaceutical Form: Prolonged‐release tablet INN or Proposed INN: Lyrinel XL CAS Number: 5633‐20‐5 Current Sponsor code: Oxybutynin Hydrochloride Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 5‐ Trade Name: Lyrinel XL Product Code: Oxybutynin hydrochloride Pharmaceutical Form: Prolonged‐release tablet INN or Proposed INN: Lyrinel XL CAS Number: 5633‐20‐5 Current Sponsor code: Oxybutynin Hydrochloride Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 10‐ Product Name: fesoterodine Pharmaceutical Form: Capsule, hard INN or Proposed INN: Fesoterodine Fumarate CAS Number: 286930‐03‐8 Other descriptive name: FESOTERODINE FUMARATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2‐ Product Name: fesoterodine Pharmaceutical Form: Capsule, hard INN or Proposed INN: Fesoterodine Fumarate CAS Number: 286930‐03‐8 Other descriptive name: FESOTERODINE FUMARATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 4‐ CONDITION: Neurogenic Detrusor Overactivity (NDO). ; MedDRA version: 20.0 Level: PT Classification code 10029279 Term: Neurogenic bladder System Organ Class: 10038359 ‐ Renal and urinary disorders Therapeutic area: Diseases [C] ‐ Symptoms and general pathology [C23] PRIMARY OUTCOME: Main Objective: To determine the safety and efficacy of fesoterodine 4 mg and 8 mg following once daily treatment for 12 weeks in pediatric NDO subjects with weight >25 kg.; To determine the safety and efficacy of fesoterodine 2 mg and 4 mg following once daily treatment for 12 weeks in pediatric NDO subjects with weight = 25 kg. Primary end point(s): Maximum cystometric bladder capacity defined as maximal tolerable cystometric capacity or until voiding/leaking begins or at 40 cm H2O. Secondary Objective: The secondary objectives of this study are to:; • evaluate the safety and efficacy of fesoterodine versus oxybutynin in pediatric NDO subjects with weight >25 kg; • evaluate the safety of fesoterodine 4 mg and 8 mg once daily treatment for up to 24 weeks in pediatric NDO subjects with weight >25 kg; • evaluate the safety of fesoterodine 2 mg and 4 mg once daily treatment for up to 24 weeks in pediatric NDO subjects with weight =25 kg.; • determine the steady‐state population pharmacokinetics of 5‐HMT following fesoterodine 4 mg and 8 mg once daily treatment in pediatric NDO subjects with weight >25 kg.; • determine the steady‐state population pharmacokinetics of 5‐HMT following treatment with two doses of fesoterodine 2 mg and 4 mg once daily in pediatric NDO subjects. Timepoint(s) of evaluation of this end point: Maximum cystometric bladder capacity (urodynamics) ‐ Visits 2 & 5 SECONDARY OUTCOME: Secondary end point(s): Efficacy Endpoints ; • Detrusor pressure at maximum bladder capacity. ; • Presence of involuntary detrusor contractions (IDC). ; • Bladder volume at first IDC. ; • Bladder compliance. ; • Mean number of micturitions and/or catheterizations/24 hrs. ; • Mean number of incontinence episodes/24 hrs. ; • Mean urgency episodes/24 hrs if applicable (only for sensate subjects). ; • Mean volume voided per micturition or mean volume per catheterization. ; Safety Endpoints ; • Adverse events, including monitoring of targeted events including, but not limited to: ; • Anticholinergic effects such as dry mouth, dry eyes and constipation. ; • CNS effects such as behavioral changes (eg, aggression), decreased cognitive function, headache, seizures, somnolence. ; • Visual effects such as accommodation disorder, blurred vision, and amblyopia. ; • Visual acuity and accommodation tests. ; • Cognitive function by the Child Behavior CheckList and Grooved Pegboard Test. ; • Vital Signs, including heart rate in the context of age‐appropriate norms. ; • Urinary Tract Infection, as evidenced by urinalysis, urine microscopy, culture and sensitivity. ; • Clinical Laboratory Evaluations in the context of age‐appropriate norms, with particular reference to liver function tests and renal chemistry. ; • Post‐void residual volume (PVR) in subjects not performing CIC, or with >1 urinary tract infection (UTI) during the study. ; Pharmacokinetic Endpoints ; • Model‐based pharmacokinetic parameter estimates for absorption rate constant (Ka), apparent oral clearance (CL/F) and volumes of distribution (Vd) to predict the area under the curve (AUC), maximum concentration (Cmax), time to reach Cmax (Tmax) and half‐life of 5‐HMT. Timepoint(s) of evaluation of this end point: Urodynamic endpoints at Visits 2 & 5 ; ediary endpoints = Visits 2 & 5 ; PinQ endpoint = Visits 2 & 5 ; Vital Signs, including heart rate.= Visits 1, 2, 3, 5 & 7 ; Adverse events = Visits 2, 3 , 4, 5, 6, 7 & 8 (Also, weeks 1, 2 & 3 for oxybutynin subjects) ; Clinical Laboratory Evaluations =Visits 1, 2, 3, 5, & 7 ; Post‐void residual volume (PVR) in subjects not performing CIC, or with >1 urinary tract ; infection (UTI) during the study= Visits 1, 2 ,3, 5 & 7 ; Pharmacokinetic Endpoints = Visit 5 ( 3 samples) INCLUSION CRITERIA: Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the study: 1. Male or female subjects aged 6 to 16 years 11 months (age at time of first dose); that is subjects who have passed their sixth birthday but not reached their seventeenth birthday. 2. Subjects with stable neurological disease and clinically‐ or urodynamically‐demonstrated NDO, confirmed urodynamically at Visit 2, by detrusor overactivity or decreased bladder compliance, with decreased maximum cystometric bladder capacity. NOTE: Subjects with hypocontractile bladder, detrusor underactivity, or a 'flaccid' bladder should not be included. 3. Evidence of a personally signed and dated informed consent document indicating that the subject or a legally acceptable representative (or representatives, as per local regulatory and legal requirements) has been informed of all pertinent aspects of the study. In addition, an assent from the subject will