A Study To Find Out How Fesoterodine Works In Children Aged 6 To 17 Years With Bladder Overactivity Caused By A Neurological Condition

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)

The objective of the study is to find out if the medicine fesoterodine is a useful treatment in children with bladder muscle overactivity caused by a neurological condition. Children will be aged 6 to 17 years old. This is done by finding out how well it works, what the body does to fesoterodine, what side effects are experienced and the safety of fesoterodine. It will be compared with the medicine oxybutynin, which is already available for treating the condition.

Study Overview

• Status: Completed
• Conditions: Urinary Bladder, Neurogenic
• Intervention / Treatment: Drug: Fesoterodine PR 4 mg; Drug: Fesoterodine PR 8 mg; Drug: Fesoterodine PR 8 mg; Drug: Oxybutynin; Drug: Fesoterodine PR; Drug: Fesoterodine BIC 2 mg; Drug: Fesoterodine BIC 4 mg

• Study Type: Interventional
• Enrollment (Actual): 181
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Universitair Ziekenhuis Antwerpen, Urologie
  • Bruxelles-capitale
    • Bruxelles, Bruxelles-capitale, Belgium, 1020
      • Hôpital Universitaire des Enfants Reine Fabiola
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3T 1C5
      • Centre hospitalier universitaire (CHU) Sainte-Justine
• Estonia
  • Tallinn, Estonia, 13419
    • Tallinn Children's Hospital
• Finland
  • Tampere, Finland, 33520
    • Tampere university Hospital
• France
  • Bron Cedex, France, 69677
    • Centre d'Investigation Clinique
  • Bron Cedex, France, 69677
    • Groupement Hospitalier Est - Hôpital Femme Mère Enfant
  • Nice, France, 06200
    • Hôpitaux Pédiatriques de Nice CHU-Lenval
• Germany
  • Nordrhein-westfalen
    • Mönchengladbach, Nordrhein-westfalen, Germany, 41063
      • Kliniken Maria Hilf GmbH
• Greece
  • Larissa, Greece, 41110
    • University General Hospital of Larisa/ Urology Department
  • Thessaloniki, Greece, 56429
    • Aristotle University Of Thessaloniki
• India
  • Punjab
    • Ludhiana, Punjab, India, 141 008
      • Department of Pediatrics, Christian Medical College and Hospital
• Italy
  • Cagliari, Italy, 09134
    • Azienda Ospedaliera G. Brotzu, Dipartimento di Medicina interna-
  • Firenze, Italy, 50139
    • Azienda Ospedaliera Universitaria Careggi
  • Roma, Italy, 00165
    • IRCCS Ospedale Pediatrico Bambino Gesu
  • Vicenza, Italy, 36100
    • ULSS 6 VICENZA - Ospedale San Bortolo di Vicenza
  • Foggia
    • San Giovanni Rotondo, Foggia, Italy, 71013
      • I.R.C.C.S. - Ospedale "Casa Sollievo della Sofferenza" - Dipartimento Scienze Chirurgiche
• Japan
  • Aichi
    • Obu, Aichi, Japan, 474 8710
      • Aichi Children's Health and Medical Center
  • Chiba, Japan
    • Chiba-shi, Chiba, Japan, Japan, 266-0007
      • Chiba Children's Hospital
  • Fukuoka
    • Fukuoka-shi, Fukuoka, Japan, 813-0017
      • Fukuoka Children's Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8648
      • Hokkaido University Hospital
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0047
      • Hyogo prefectural Kobe Children's Hospital
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 232-8555
      • Kanagawa Children's Medical Center
  • Nagano
    • Matsumoto, Nagano, Japan, 3908621
      • Shinshu University Hospital
  • Osaka
    • Izumi-shi, Osaka, Japan, 594-1101
      • Osaka Medical Center and Research Institute for Maternal and Child Health
  • Saitama
    • Koshigaya, Saitama, Japan, 343-8555
      • Dokkyo Medical University Koshigaya Hospital
  • Shizuoka
    • Shizuoka-shi, Shizuoka, Japan, 420 8660
      • Shizuoka Children's Hospital
  • Tochigi
    • Shimotsuga-gun, Tochigi, Japan, 321 0293
      • Dokkyo Medical University Hospital / Urology
    • Shimotsuke, Tochigi, Japan, 329 0498
      • Jichi Medical University Hospital
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8655
      • The University of Tokyo Hospital / Urology
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Gyeongsangnam-do
    • Yangsan-si, Gyeongsangnam-do, Korea, Republic of, 50612
      • Pusan National University Yangsan Hospital
  • Korea
    • Seoul, Korea, Korea, Republic of, 08308
      • Korea University Guro Hospital
• Lithuania
  • Kaunas, Lithuania, LT-50161
    • Hospital of Lithuanian University of Health Sciences Kaunas klinikos
  • Vilnius, Lithuania, LT-08406
    • Children's Hospital, Affiliate of Vilnius University Hospital Santaros Klinikos
• Malaysia
  • Kuala Lumpur, Malaysia, 50586
    • Hospital Kuala Lumpur
  • Selangor
    • Batu Caves, Selangor, Malaysia, 68100
      • Hospital Selayang
• Philippines
  • NCR
    • Quezon City, NCR, Philippines, 1100
      • Philippine Children's Medical Center
• Poland
  • Gdansk, Poland, 80-952
    • Klinika Chorob Nerek i Nadcisnienia Dzieci i Mlodziezy
  • Poznan, Poland, 61-512
    • Specjalistyczny Gabinet Lekarski Paweł Kroll
• Russian Federation
  • Kazan, Russian Federation, 420138
    • Children's Republican Clinical Hospital, Department of Pediatric Surgery
  • Moscow, Russian Federation, 105425
    • Scientific Research Institute of Urology named after N.A.Lopatkin of the Hertsen Federal Medical
  • Moscow, Russian Federation, 119991
    • FGBNU Scientific center of children health
  • Moscow, Russian Federation, 125412
    • SSS - Research Clinical Institute of Pediatrics n.a. Academician Y.E.Veltishchev GBOU VPO
  • Republic OF Tatarstan
    • Kazan, Republic OF Tatarstan, Russian Federation, 420012
      • Kazan State Medical University
• Slovakia
  • Bratislava, Slovakia, 833 40
    • Narodny ustav detskych chorob
  • Bratislava, Slovakia, 831 01
    • J. BREZA MEDICAL s.r.o.
• South Africa
  • Western CAPE
    • Cape Town, Western CAPE, South Africa, 7700
      • Red Cross Children'S Hospital
• Spain
  • Madrid, Spain, 28009
    • Hospital Infantil Universitario Niño Jesús
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañon
  • Malaga, Spain, 29011
    • Hospital Regional Universitario Carlos Haya
  • Valencia, Spain, 46026
    • Hospital Universitari i Politecnic La Fe
  • Barcelona
    • Esplugues de Llobregat, Barcelona, Spain, 08950
      • Hospital Sant Joan de Déu
• Sweden
  • Uppsala, Sweden, 751 85
    • Akademiska Barnsjukhuset
• Switzerland
  • Basel, Switzerland, 4031
    • Universitäts-Kinderspital beider Basel
• Taiwan
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
• Turkey
  • Ankara, Turkey, 06100
    • Ankara Universitesi Tip Fakultesi Ibni Sina Hastanesi
  • Ankara, Turkey, 06100
    • Hacettepe Universitesi Tip Fakultesi Uroloji Anabilim Dali
  • Istanbul, Turkey, 34390
    • Istanbul Universitesi Istanbul Tip Fakultesi
  • Konya / Turkey
    • Konya, Konya / Turkey, Turkey, 42080
      • Necmettin Erbakan Universitesi Meram Tip Fakultesi
• United Kingdom
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary
  • Liverpool, United Kingdom, L12 2AP
    • Alder Hey Children's Hospital
  • Sheffield, United Kingdom, S10 2TH
    • Sheffield Children's NHS Foundation Trust
• United States
  • Arizona
    • Tucson, Arizona, United States, 85715
      • Urological Associates of Southern Arizona
  • California
    • Orange, California, United States, 92868
      • Childrens Hospital of Orange County
    • Orange, California, United States, 92868
      • CHOC Children's Urology Center
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Children's Healthcare of Atlanta
    • Atlanta, Georgia, United States, 30342
      • Georgia Urology, P.A.
    • Atlanta, Georgia, United States, 30342
      • Judson L. Hawk Jr. M.D.
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Maywood, Illinois, United States, 60153
      • Loyola University Outpatient Center
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • The Iowa Clinic
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • UNC Chapel Hill Memorial Hospital
    • Chapel Hill, North Carolina, United States, 27514
      • UNC Memorial Hospital Pediatric Clinic
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
    • Liberty Township, Ohio, United States, 45044
      • Cincinnati Children's Hospital Medical Center
  • Rhode Island
    • East Providence, Rhode Island, United States, 02915
      • Pharma Resource
    • East Providence, Rhode Island, United States, 02914
      • Advanced Radiology
    • Providence, Rhode Island, United States, 02904
      • University Urological Associates, Inc
    • Providence, Rhode Island, United States, 02905
      • University Urological Associates, Inc.
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Children's Hospital of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects aged 6 to 17 years old
• Subjects with stable neurological disease and neurogenic detrusor overactivity
• Subjects using clean intermittent catheterization may participate

Exclusion Criteria:

• Concomitant medications which may increase the risk to subjects or confound study results
• Other medical conditions which may increase the risk to subjects or confound study results
• Contraindications to the use of fesoterodine or oxybutynin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fesoterodine PR 4 mg; Fesoterodine PR 4 mg for 12 weeks in active comparator period, followed by 12 weeks in safety extension period	Drug: Fesoterodine PR 4 mg; Fesoterodine 4 mg tablet once daily for 24 weeks
Experimental: Fesoterodine PR 8 mg; Fesoterodine 8 mg for first week followed by 11 weeks at 8 mg in active control period, followed by 12 weeks in safety extension period.	Drug: Fesoterodine PR 8 mg; Fesoterodine PR 8 mg tablet once daily for 24 weeks, the first week being 4 mg.; Drug: Fesoterodine PR 8 mg; Fesoterodine 8 mg tablet once daily for 24 weeks, the first week being 4 mg.
Active Comparator: Oxybutynin	Drug: Oxybutynin; Oxybutynin extended release tablets according to approved pediatric labeling for 12 weeks with dose titration phase for first 4 weeks to achieve dose optimisation.; Drug: Fesoterodine PR; Fesoterodine 4 mg or 8 mg tablets once daily for 12 weeks after 12 weeks of oxybutinin. Those assigned to 8 mg will take 4 mg for the first week.; Other Names: Safety extension phase
Experimental: Fesoterodine BIC 2 mg; Fesoterodine BIC 2 mg for 12 weeks in efficicay period, followed by 12 weeks in safety extension period.	Drug: Fesoterodine BIC 2 mg; Fesoterodine BIC 2 mg tablet once daily for 24 weeks.
Experimental: Fesoterodine BIC 4 mg; Fesoterodine BIC 4 mg for first week followed by 11 weeks at 8 mg in the efficacy period, followed by 12 weeks in safety extension period.	Drug: Fesoterodine BIC 4 mg; Fesoterodine BIC 4 mg tablet once daily for 24 weeks, with the first week being 2 mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Maximum Cystometric Bladder Capacity at Week 12: Active Comparator Phase/Efficacy Phase	Maximum cystometric bladder capacity (in milliliter) was defined as maximal tolerable cystometric capacity, until voiding or leaking begins or at a pressure of >=40 centimeter (cm) water (H2O).	Baseline, Week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Detrusor Pressure at Maximum Bladder Capacity at Week 12: Active Comparator Phase/Efficacy Phase	Detrusor pressure (in cm H2O) at maximum urinary bladder capacity was measured using urodynamic testing.	Baseline, Week 12
Number of Participants With Shift From Baseline at Week 12 in Involuntary Detrusor Contractions (IDC): Active Comparator Phase/Efficacy Phase	In this outcome measure, shift data have been reported using 4 categories: (1) number of participants who did not have IDC at Baseline and at Week 12, (2) number of participants who did not have IDC at Baseline but had IDC at Week 12, (3) number of participants who had IDC at Baseline but no IDC at Week 12, and (4) number of participants who had IDC at Baseline and at Week 12.	Baseline, Week 12
Change From Baseline in Bladder Volume at First Involuntary Detrusor Contraction (IDC) at Week 12: Active Comparator Phase/Efficacy Phase	Bladder volume (in milliliter) at first IDC was measured using urodynamic testing.	Baseline, Week 12
Change From Baseline in Bladder Compliance at Week 12: Active Comparator Phase/Efficacy Phase	Bladder compliance was defined as change in bladder volume in milliliter (mL) divided by change in bladder pressure in cm H2O (during the same time when change in bladder volume was estimated).	Baseline, Week 12
Change From Baseline in Mean Number of Micturitions Per 24 Hours at Week 12: Active Comparator Phase/Efficacy Phase	The mean number of micturitions per 24 hours were calculated as the total number of micturitions divided by the total number of diary days collected at the assessment time point. Number of diary days collected at the assessment time point = number of calendar days when the diary was completed on, even if it was not a full 24 hour period. This outcome measure was only calculated for participants with >0 micturitions at Baseline.	Baseline, Week 12
Change From Baseline in Mean Number of Catheterizations Per 24 Hours at Week 12: Active Comparator Phase/Efficacy Phase	The mean number of catheterizations per 24 hours were calculated as the total number of catheterizations divided by the total number of diary days collected at the assessment time point. Number of diary days collected at the assessment time point = number of calendar days when the diary was completed on; even if it was not a full 24 hours period. This outcome measure was only calculated for participants with >0 catheterizations at Baseline.	Baseline, Week 12
Change From Baseline in Mean Number of Micturitions or Catheterizations Per 24 Hours at Week 12: Active Comparator Phase/Efficacy Phase	The mean number of micturitions or catheterizations combined per 24 hours were calculated as the total number of micturitions and catheterizations combined divided by the total number of diary days collected at the assessment point. Number of diary days collected at the assessment time point = number of calendar days when the diary was completed; even if it was not a full 24 hour (hrs) period. This outcome was evaluated in those participants who had micturitions or catheterizations >0 at Baseline.	Baseline, Week 12
Change From Baseline in Mean Number of Incontinence Episodes Per 24 Hours at Week 12: Active Comparator Phase/Efficacy Phase	The mean number of incontinence episodes per 24 hours were calculated as the total number of incontinence episodes divided by the total number of diary days collected at the assessment time point. Number of diary days collected at the assessment time point = number of calendar days when the diary was completed; even if it was not a full 24 hours period. This outcome measure was only calculated for participants with >0 incontinence episodes at Baseline.	Baseline, Week 12
Change From Baseline in Mean Number of Urgency Episodes Per 24 Hours at Week 12: Active Comparator Phase/Efficacy Phase	The mean number of urgency episodes per 24 hours were calculated as the total number of urgency episodes divided by the total number of diary days collected at the assessment time point. Number of diary days collected at the assessment time point = number of calendar days when the diary was completed; even if it was not a full 24 hours period. Urgency episodes were defined as urgency marked as 'yes' in the diary. This outcome measure was only calculated for participants with >0 urgency episodes at Baseline.	Baseline, Week 12
Change From Baseline in Mean Volume Voided Per Micturition at Week 12: Active Comparator Phase/Efficacy Phase	The mean voided volume per micturition was calculated as sum of voided volume divided by the total number of micturition episodes with a recorded voided volume greater than 0.	Baseline, Week 12
Change From Baseline in Mean Volume Voided Per Catheterization at Week 12: Active Comparator Phase/Efficacy Phase	The mean volume per catheterization was calculated as sum of voided volume divided by the total number of catheterization, with a recorded voided volume greater than 0.	Baseline, Week 12
Change From Baseline in Mean Volume Voided Per Micturition or Catheterization at Week 12: Active Comparator Phase/Efficacy Phase	The mean voided volume per micturition or catheterization was calculated as sum of voided volume divided by the total number of micturition or catheterization episodes with a recorded voided volume greater than 0. This outcome was evaluated in those participants who had micturitions or catheterizations >0 at Baseline.	Baseline, Week 12
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Active Comparator Phase/Efficacy Phase	An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both all serious and non-serious adverse events.	Baseline up to Week 12
Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Safety Extension Phase	An AE was any untoward medical occurrence in a participant who received investigational product without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly; medically important events. A treatment emergent AE was defined as an event that emerged during the treatment period that was absent before treatment, or worsened during the treatment period relative to the pretreatment state. AEs included both all serious and non-serious adverse events.	Week 12 up to Week 26 (including 2 weeks of follow up after last dose)
Change From Baseline in Visual Acuity at Week 12: Active Comparator Phase/Efficacy Phase	Visual acuity (VA) was assessed using the Snellen method, where logarithm of minimum angle of resolution (logMAR) units were derived from the Snellen ratios. Participants had to read letters from the chart at a distance of 20 feet/6 meter or 4 meter. VA/Snellen ratio = distance between the chart and participant, divided by the distance at which participant was able to see or read chart without impairment; expressed as decimal. logMAR = log10 (1/decimal VA). In this outcome measure data have been reported for right and left eye separately.	Baseline, Week 12
Change From Baseline in Visual Acuity at Week 24: Safety Extension Phase	VA was assessed using the Snellen method, where logMAR units were derived from the Snellen ratios. Participants had to read letters from the chart at a distance of 20 feet/6 meter or 4 meter. VA/Snellen ratio = distance between the chart and participant, divided by the distance at which participant was able to see or read chart without impairment; expressed as decimal. logMAR = log10 (1/decimal VA). In this outcome measure data have been reported for right and left eye separately.	Baseline, Week 24
Change From Baseline in Visual Accommodation at Week 12: Active Comparator Phase/Efficacy Phase	The visual accommodation was the distance for each eye at which vision became blurred and was calculated as the mean of triplicate measurements. The participants focused on a single letter of the 20/40 line of an eye chart and chart was moved slowly towards the participant until letter was blurred. At this point, the distance from eye to letter was measured for each eye. In this outcome measure data have been reported for right and left eye separately.	Baseline, Week 12
Change From Baseline in Visual Accommodation at Week 24: Safety Extension Phase	The visual accommodation is the distance for each eye at which vision became blurred and was calculated as the mean of triplicate measurements. The participants focused on a single letter of the 20/40 line of an eye chart and chart was moved slowly towards the participant until letter was blurred. At this point, the distance from eye to letter was measured for each eye. In this outcome measure data have been reported for right and left eye separately.	Baseline, Week 24
Change From Baseline in Child Behavior Checklist (CBCL) T Score (Derived Score) at Week 12: Active Comparator Phase/Efficacy Phase	CBCL: 120 items questionnaire answered by parent/caregiver of child to assess a child's behavioral, emotional problems. Scale for each item: 0= not true, 1= somewhat/sometimes true, 2= very true/often true. Out of 120 items, 103 were categorized into 8 domains; aggressive behavior, anxious/depressed, attention problems, rule-breaking behavior, social problems, somatic complaints, thought problems, withdrawn. Summary scores: Internalizing problems=anxious/depressed + withdrawn + somatic complaints; Externalizing problems=rule-breaking + aggressive behavior. Total problems=8 domains + other 17 items. Raw scores for each domain, summary and total problems=sum of scores of related items. Using Assessment Data Manager (ADM) tool raw scores transformed/derived into standard T-scores, range: each domain=50 to 100, internalizing problems=34 to 100, externalizing problems=33 to 100, total problems=24 to 100. Lower T-score for each 8 domains, 2 summary and total problems scores=better outcomes.	Baseline, Week 12
Change From Baseline in Child Behavior Checklist (CBCL) T Score (Derived Score) at Week 24: Safety Extension Phase	CBCL: 120 items questionnaire answered by parent/caregiver of child to assess a child's behavioral, emotional problems. Scale for each item: 0= not true, 1= somewhat/sometimes true, 2= very true/often true. Out of 120 items, 103 were categorized into 8 domains; aggressive behavior, anxious/depressed, attention problems, rule-breaking behavior, social problems, somatic complaints, thought problems, withdrawn. Summary scores: Internalizing problems=anxious/depressed + withdrawn + somatic complaints; Externalizing problems=rule-breaking + aggressive behavior. Total problems=8 domains + other 17 items. Raw scores for each domain, summary and total problems=sum of scores of related items. Using Assessment Data Manager (ADM) tool raw scores transformed/derived into standard T-scores, range: each domain=50 to 100, internalizing problems=34 to 100, externalizing problems=33 to 100, total problems=24 to 100. Lower T-score for each 8 domains, 2 summary and total problems scores=better outcomes.	Baseline, Week 24
Change From Baseline in Child Behavior Checklist Total Score (Raw Score) at Week 12: Active Comparator Phase/Efficacy Phase	CBCL: It consisted of 120 items on behavior and emotional problems. Parent/caregiver of child answered 120 items, each on scale: 0= not true, 1= somewhat/sometimes true, 2= very/often true. 103 items were classified in 8 domains: aggressive behavior: total score range (TSR)= 0 to 36, anxious/depressed: TSR= 0 to 26, attention problems: TSR= 0 to 20, rule-breaking behavior: TSR= 0 to 34, social problems: TSR= 0 to 22, somatic complaints: TSR= 0 to 22, thought problems: TSR= 0 to 30, withdrawn (TSR)= 0 to 16. Rule-breaking and aggressive behavior summarized to externalizing problems with a TSR= 0 to 70. Anxious/depressed, withdrawn, somatic complaints summarized to internalizing problems with a TSR= 0 to 64. All 103 items of 8 domains and other 17 remaining items were combined to give total problems TSR = 0 to 240. TSR for each domain, summary and total problems was sum of scores of related items respectively. Lower scores for each domain, summary and total problems= better outcomes.	Baseline, Week 12
Change From Baseline in Child Behavior Checklist Total Score (Raw Score) at Week 24: Safety Extension Phase	CBCL: It consisted of 120 items on behavior and emotional problems. Parent/caregiver of child answered 120 items, each on scale: 0= not true, 1= somewhat/sometimes true, 2= very/often true. 103 items were classified in 8 domains: aggressive behavior: total score range (TSR)= 0 to 36, anxious/depressed: TSR= 0 to 26, attention problems: TSR= 0 to 20, rule-breaking behavior: TSR= 0 to 34, social problems: TSR= 0 to 22, somatic complaints: TSR= 0 to 22, thought problems: TSR= 0 to 30, withdrawn (TSR)= 0 to 16. Rule-breaking and aggressive behavior summarized to externalizing problems with a TSR= 0 to 70. Anxious/depressed, withdrawn, somatic complaints summarized to internalizing problems with a TSR= 0 to 64. All 103 items of 8 domains and other 17 remaining items were combined to give total problems TSR = 0 to 240. TSR for each domain, summary and total problems was sum of scores of related items respectively. Lower scores for each domain, summary and total problems= better outcomes.	Baseline, Week 24
Change From Baseline in Time to Completion Assessment of Grooved Pegboard Test, 10 Pegs Group at Week 12: Active Comparator Phase/Efficacy Phase	The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. It consisted of a small board of 25 holes with randomly positioned slots. Pegs with a key along one side must be rotated to match the hole before they can be inserted. In this outcome measure participants were asked to insert 10 grooved pegs into the holes within the given time limit (up to 300 seconds). The task needs to be completed once for each hand; firstly, using the dominant hand followed by the non-dominant hand. Time taken to complete the test was inversely correlated to the cognitive ability.	Baseline, Week 12
Change From Baseline in Time to Completion Assessment of Grooved Pegboard Test, 10 Pegs Group at Week 24: Safety Extension Phase	The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. It consisted of a small board of 25 holes with randomly positioned slots. Pegs with a key along one side must be rotated to match the hole before they can be inserted. In this outcome measure participants were asked to insert 10 grooved pegs into the holes within the given time limit (up to 300 seconds). The task needs to be completed once for each hand; firstly, using the dominant hand followed by the non-dominant hand. Time taken to complete the test was inversely correlated to the cognitive ability.	Baseline, Week 24
Change From Baseline in Time to Completion Assessment of Grooved Pegboard Test, 25 Pegs Group at Week 12: Active Comparator Phase/Efficacy Phase	The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. It consisted of a small board of 25 holes with randomly positioned slots. Pegs with a key along one side must be rotated to match the hole before they can be inserted. In this outcome measure participants were asked to insert 25 grooved pegs into the holes within the given time limit (up to 300 seconds). The task needs to be completed once for each hand; firstly, using the dominant hand followed by the non-dominant hand. Time taken to complete the test was inversely correlated to the cognitive ability.	Baseline, Week 12
Change From Baseline in Time to Completion Assessment of Grooved Pegboard Test, 25 Pegs Group at Week 24: Safety Extension Phase	The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. It consisted of a small board of 25 holes with randomly positioned slots. Pegs with a key along one side must be rotated to match the hole before they can be inserted. In this outcome measure participants were asked to insert 25 grooved pegs into the holes within the given time limit (up to 300 seconds). The task needs to be completed once for each hand; firstly, using the dominant hand followed by the non-dominant hand. Time taken to complete the test was inversely correlated to the cognitive ability.	Baseline, Week 24
Change From Baseline in Number of Pegs Dropped Assessment of Grooved Pegboard Test, 10 Pegs Group at Week 12: Active Comparator Phase/Efficacy Phase	The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. It consisted of a small board of 25 holes with randomly positioned slots. Pegs with a key along one side must be rotated to match the hole before they can be inserted. Participants were asked to insert 10 grooved pegs into the holes within the given time limit (up to 300 seconds). In this outcome measure number of pegs dropped while putting in the holes were measured. The task needs to be completed once for each hand; firstly, using the dominant hand followed by the non-dominant hand.	Baseline, Week 12
Change From Baseline in Number of Pegs Dropped Assessment of Grooved Pegboard Test, 10 Pegs Group at Week 24: Safety Extension Phase	The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. It consisted of a small board of 25 holes with randomly positioned slots. Pegs with a key along one side must be rotated to match the hole before they can be inserted. Participants were asked to insert 10 grooved pegs into the holes within the given time limit (up to 300 seconds). In this outcome measure number of pegs dropped while putting in the holes were measured. The task needs to be completed once for each hand; firstly, using the dominant hand followed by the non-dominant hand.	Baseline, Week 24
Change From Baseline in Number of Pegs Dropped Assessment of Grooved Pegboard Test, 25 Pegs Group at Week 12: Active Comparator Phase/Efficacy Phase	The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. It consisted of a small board of 25 holes with randomly positioned slots. Pegs with a key along one side must be rotated to match the hole before they can be inserted. Participants were asked to insert 25 grooved pegs into the holes within the given time limit (up to 300 seconds). In this outcome measure number of pegs dropped while putting in the holes were measured. The task needs to be completed once for each hand; firstly, using the dominant hand followed by the non-dominant hand.	Baseline, Week 12
Change From Baseline in Number of Pegs Dropped Assessment of Grooved Pegboard Test, 25 Pegs Group at Week 24: Safety Extension Phase	The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. It consisted of a small board of 25 holes with randomly positioned slots. Pegs with a key along one side must be rotated to match the hole before they can be inserted. Participants were asked to insert 25 grooved pegs into the holes within the given time limit (up to 300 seconds). In this outcome measure number of pegs dropped while putting in the holes were measured. The task needs to be completed once for each hand; firstly, using the dominant hand followed by the non-dominant hand.	Baseline, Week 24
Change From Baseline in Number of Pegs Placed Correctly Assessment of Grooved Pegboard Test, 10 Pegs Group at Week 12: Active Comparator Phase/Efficacy Phase	The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. It consisted of a small board of 25 holes with randomly positioned slots. Pegs with a key along one side must be rotated to match the hole before they can be inserted. Participants were asked to insert 10 grooved pegs into the holes within the given time limit (up to 300 seconds). In this outcome measure number of pegs placed correctly while putting in the holes were measured. The task needs to be completed once for each hand; firstly, using the dominant hand followed by the non-dominant hand.	Baseline, Week 12
Change From Baseline in Number of Pegs Placed Correctly Assessment of Grooved Pegboard Test, 10 Pegs Group at Week 24: Safety Extension Phase	The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. It consisted of a small board of 25 holes with randomly positioned slots. Pegs with a key along one side must be rotated to match the hole before they can be inserted. Participants were asked to insert 10 grooved pegs into the holes within the given time limit (up to 300 seconds). In this outcome measure number of pegs placed correctly while putting in the holes were measured. The task needs to be completed once for each hand; firstly, using the dominant hand followed by the non-dominant hand.	Baseline, Week 24
Change From Baseline in Number of Pegs Placed Correctly Assessment of Grooved Pegboard Test, 25 Pegs Group at Week 12: Active Comparator Phase/Efficacy Phase	The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. It consisted of a small board of 25 holes with randomly positioned slots. Pegs with a key along one side must be rotated to match the hole before they can be inserted. Participants were asked to insert 25 grooved pegs into the holes within the given time limit (up to 300 seconds). In this outcome measure number of pegs placed correctly while putting in the holes were measured. The task needs to be completed once for each hand; firstly, using the dominant hand followed by the non-dominant hand.	Baseline, Week 12
Change From Baseline in Number of Pegs Placed Correctly Assessment of Grooved Pegboard Test, 25 Pegs Group at Week 24: Safety Extension Phase	The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. It consisted of a small board of 25 holes with randomly positioned slots. Pegs with a key along one side must be rotated to match the hole before they can be inserted. Participants were asked to insert 25 grooved pegs into the holes within the given time limit (up to 300 seconds). In this outcome measure number of pegs placed correctly while putting in the holes were measured. The task needs to be completed once for each hand; firstly, using the dominant hand followed by the non-dominant hand.	Baseline, Week 24
Number of Participants Meeting Pre-defined Criteria for Vital Signs Values From Baseline Through Week 12: Active Comparator/Efficacy Phase	Pre-defined criteria for vital signs: 1) a) systolic blood pressure (SBP) of <90 millimeter of mercury (mmHg), b) change >=30 mmHg increase, c) change >=30 mmHg decrease; 2) a) diastolic blood pressure (DBP) of <50 mmHg, b) change >=20 mmHg increase, c) change >=20 mmHg decrease; 3) a) pulse rate value of <40 beats per minute (bpm), b) pulse rate value >120 bpm.	Baseline up to Week 12
Number of Participants Meeting Pre-defined Criteria for Vital Signs Values From Baseline Through Week 24: Safety Extension Phase	Pre-defined criteria for vital signs: 1) a) systolic blood pressure (SBP) of <90 millimeter of mercury (mmHg), b) change >=30 mmHg increase, c) change >=30 mmHg decrease; 2) a) diastolic blood pressure (DBP) of <50 mmHg, b) change >=20 mmHg increase, c) change >=20 mmHg decrease; 3) a) pulse rate value of <40 beats per minute (bpm), b) pulse rate value >120 bpm.	Baseline up to Week 24
Number of Participants With Clinically Significant Urinary Tract Infections (UTI): Active Comparator/Efficacy Phase	Clinically significant UTI, counted as an adverse event was defined as: positive urine culture with a uropathogen (defined as >=10^5 colony forming unit per milliliter [CFU/mL]) and the presence of symptoms, or pyuria (defined as >50 white blood cells [WBC] per high-pass filter [hpf]) and the presence of symptoms, or positive urine culture with a uropathogen (defined as >=10^5 CFU/mL) with or without symptoms in a participant with a documented history of vesicoureteral reflux (VUR).	Week 1 up to Week 12
Number of Participants With Clinically Significant Urinary Tract Infections (UTI): Safety Extension Phase	Clinically significant UTI, counted as an adverse event was defined as: positive urine culture with a uropathogen (defined as >=10^5 CFU/mL) and the presence of symptoms, or pyuria (defined as >50 WBC per hpf and the presence of symptoms, or positive urine culture with a uropathogen (defined as >=10^5 CFU/mL) with or without symptoms in a participants with a documented history of VUR.	Week 12 up to Week 26
Number of Participants With Clinical Laboratory Abnormalities: Active Comparator/Efficacy Phase	Hematology: hemoglobin, hematocrit, erythrocytes <0.8*lower limit of normal (LLN), platelets<0.5*LLN>1.75*upper limit of normal (ULN), leukocytes <0.6*LLN>1.5*ULN, lymphocytes, neutrophils, <0.8*LLN >1.2*ULN, basophils, eosinophils, monocytes monocytes/leukocytes >1.2*ULN. Clinical chemistry: bilirubin, direct, bilirubin >1.5*ULN, aspartate aminotransferase (AT), alanine AT, gamma glutamyl transferase, lactate dehydrogenase, alkaline phosphatase>3.0*ULN, protein, albumin, phosphate <0.8*LLN >1.2*ULN, blood urea nitrogen, creatinine >1.3*ULN, urate >1.2*ULN, sodium<0.95*LLN>1.05*ULN, potassium, chloride, calcium bicarbonate<0.9*LLN>1.1*ULN, glucose<0.6*LLN>1.5*ULN, creatine kinase >2.0*ULN. Urinalysis: specific gravity <1.003>1.030, pH <4.5>8, urine glucose, ketones, urine protein, urine hemoglobin, urine bilirubin, nitrite, >=1, urine erythrocytes, urine leukocytes >=20, epithelial cells >=6, bacteria >20.	Week 1 up to Week 12
Number of Participants With Clinical Laboratory Abnormalities: Safety Extension Phase	Hematology: hemoglobin, hematocrit, erythrocytes <0.8*lower limit of normal (LLN), platelets<0.5*LLN>1.75*upper limit of normal (ULN), leukocytes <0.6*LLN>1.5*ULN, lymphocytes, neutrophils, <0.8*LLN >1.2*ULN, basophils, eosinophils, monocytes monocytes/leukocytes >1.2*ULN. Clinical chemistry: bilirubin, direct, bilirubin >1.5*ULN, aspartate aminotransferase (AT), alanine AT, gamma glutamyl transferase, lactate dehydrogenase, alkaline phosphatase>3.0*ULN, protein, albumin, phosphate <0.8*LLN >1.2*ULN, blood urea nitrogen, creatinine >1.3*ULN, urate >1.2*ULN, sodium<0.95*LLN>1.05*ULN, potassium, chloride, calcium bicarbonate<0.9*LLN>1.1*ULN, glucose<0.6*LLN>1.5*ULN, creatine kinase >2.0*ULN. Urinalysis: specific gravity <1.003>1.030, pH <4.5>8, urine glucose, ketones, urine protein, urine hemoglobin, urine bilirubin, nitrite, >=1, urine erythrocytes, urine leukocytes >=20, epithelial cells >=6, bacteria >20.	Week 12 up to Week 26
Change From Baseline in Post-Void Residual (PVR) Volume at Weeks 4, 12: Active Comparator Phase/Efficacy Phase	Post-void residual volume measurement was measured by an ultrasound. PVR volume was only assessed for participants who did not perform clean intermittent catheterization or in any participants who had >1 UTI during the study.	Baseline, Week 4, 12
Change From Baseline in Post-Void Residual Volume at Week 24: Safety Extension Phase	Post-void residual volume measurement was measured by an ultrasound. PVR volume was only assessed for participants who did not perform clean intermittent catheterization or in any participants who had >1 UTI during the study.	Baseline, Week 24
Number of Participants With Clinically Relevant Changes in Physical Examination Findings From Baseline to Week 12: Active Comparator/Efficacy Phase	Physical examination included assessment of the general appearance and the skin, head, ears, eyes, nose, mouth, throat, respiratory, cardiovascular, gastrointestinal, musculoskeletal and neurological systems. Clinically relevant changes in physical findings were assessed by the investigator.	Baseline up to Week 12
Number of Participants With Clinically Relevant Changes in Physical Examination Findings From Baseline to Week 24: Safety Extension Phase	Physical examination included assessment of the general appearance and the skin, head, ears, eyes, nose, mouth, throat, respiratory, cardiovascular, gastrointestinal, musculoskeletal and neurological systems. Clinically relevant changes in physical findings were assessed by the investigator.	Baseline up to Week 24
Absorption Rate Constant (Ka) of Fesoterodine	Absorption rate constant is used to determine rate at which drug is entering into body. Pharmacokinetic (PK) analysis was not done separately for each dose of fesoterodine in respective cohorts and were combined for PK analysis using PK modelling approach.	Week 4, Day 1: pre-dose (when dose administered at clinic) or if dose taken at home up to 3 hours before coming to the clinic, sampling just after arrival at clinic, 5 hours post-dose, 8-10 hours post-dose (if participants remained at clinic)
Apparent Oral Clearance (CL/F) of Fesoterodine	Clearance determines the rate at which a drug is metabolized or eliminated by normal biological processes. PK analysis was not done separately for each dose of fesoterodine in respective cohorts and were combined for PK analysis using PK modelling approach.	Week 4, Day 1: pre-dose (when dose administered at clinic) or if dose taken at home up to 3 hours before coming to the clinic, sampling just after arrival at clinic, 5 hours post-dose, 8-10 hours post-dose (if participants remained at clinic)
Volume of Distribution (Vd) of Fesoterodine	Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. PK analysis was not done separately for each dose of fesoterodine in respective cohorts and were combined for PK analysis using PK modelling approach.	Week 4, Day 1: pre-dose (when dose administered at clinic) or if dose taken at home up to 3 hours before coming to the clinic, sampling just after arrival at clinic, 5 hours post-dose, 8-10 hours post-dose (if participants remained at clinic)

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): July 2, 2012
• Primary Completion (Actual): November 7, 2019
• Study Completion (Actual): February 13, 2020

Study Registration Dates

• First Submitted: March 15, 2012
• First Submitted That Met QC Criteria: March 15, 2012
• First Posted (Estimate): March 19, 2012

Study Record Updates

• Last Update Posted (Actual): February 2, 2021
• Last Update Submitted That Met QC Criteria: January 12, 2021
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: neurogenic detrusor overactivity; fesoterodine; neurogenic bladder; neurologic disease; neuropathic bladder
• Additional Relevant MeSH Terms: Nervous System Diseases; Urologic Diseases; Urinary Bladder Diseases; Neurologic Manifestations; Urinary Bladder, Neurogenic; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Urological Agents; Oxybutynin; Fesoterodine
• Other Study ID Numbers: A0221047; 2010-022475-55 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No