Open-label Long-term Extension Study of Fesoterodine in Japanese Subjects With Neurogenic Detrusor Overactivity.

Study Overview
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Brief Summary
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The purpose of this study is to investigate the safety and tolerability of fesoterodine following once daily long-term treatment in Japanese pediatric neurogenic detrusor overactivity (NDO) subjects.

Detailed Description
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This is a Phase 3, multi-center, open-label long-term extension study in Japanese NDO subjects who participated and completed in the precedent Study A0221047 which is a 24 weeks, randomized, open label study, to investigate the safety and tolerability of fesoterodine. This study consists of a 28-week open-label treatment period followed by a 4-week follow-up. In addition, subjects in the oxybutynin arm of the precedent Study A0221047 will continue the fesoterodine treatment until Week 40 visit in this study, in order to obtain fesoterodine 1 year treatment data.

Official Title
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LONG-TERM EXTENSION STUDY TO EVALUATE THE SAFETY OF FESOTERODINE IN JAPANESE PEDIATRIC SUBJECTS WITH SYMPTOMS OF DETRUSOR OVERACTIVITY ASSOCIATED WITH A NEUROLOGICAL CONDITION (NEUROGENIC DETRUSOR OVERACTIVITY) WHO HAVE COMPLETED 24 WEEKS TREATMENT IN STUDY A0221047

Conditions
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Urinary Bladder, Neurogenic

Intervention / Treatment
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* Drug: Fesoterodine PR 4 mg
* Drug: Fesoterodine PR 8 mg
* Drug: Fesoterodine BIC 2 mg
* Drug: Fesoterodine BIC 4 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: •Subjects who completed 24 week treatment and all visit procedures in the precedent Study A0221047 Exclusion Criteria: Subjects who had major protocol violation (as determined by the Sponsor) in Study A0221047 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

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fesoterodine PR 4 mg<br>Fesoterodine PR 4 mg for 28 or 40 weeks in open-label treatment period | Drug: Fesoterodine PR 4 mg<br>* Fesoterodine 4 mg tablet once daily for 28 or 40 weeks<br>|
| Experimental: Fesoterodine PR 8 mg<br>Fesoterodine PR 8 mg for 28 or 40 weeks in open-label treatment period | Drug: Fesoterodine PR 8 mg<br>* Fesoterodine PR 8 mg tablet once daily for 28 or 40 weeks<br>|
| Experimental: Fesoterodine BIC 2 mg<br>Fesoterodine BIC 2 mg for 28 weeks in open-label treatment period | Drug: Fesoterodine BIC 2 mg<br>* Fesoterodine BIC 2 mg tablet once daily for 28 weeks<br>|
| Experimental: Fesoterodine BIC 4 mg<br>Fesoterodine BIC 4 mg for 28 weeks in open-label treatment period | Drug: Fesoterodine BIC 4 mg<br>* Fesoterodine BIC 4 mg tablet once daily for 28 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs): Merged Data of Studies A0221047 and A0221109 | 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 serious and non-serious adverse events. TEAEs were summarized for each cohort (Cohort 1 and Cohort 2, irrespective of treatment received), each treatment group and the total of treatment groups, using the merged data of studies A0221047 and A0221109 as planned. | Up to a maximum of 56 weeks (24 weeks of treatment in A0221047 and 32 weeks [28 weeks treatment + 4 weeks follow up post last dose] in A0221109) | 
| Change From Baseline in Visual Acuity at Week 12: Study A0221109 | Visual acuity (VA) was assessed for each eye 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 distance at which participant was able to see/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. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 12 | 
| Change From Baseline in Visual Acuity at Week 28: Study A0221109 | VA was assessed for each eye 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 distance at which participant was able to see/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. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 28 | 
| Change From Baseline in Visual Acuity at Final Visit: Study A0221109 | VA was assessed for each eye 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 distance at which participant was able to see/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. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Final visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Visual Accommodation at Week 12: Study A0221109 | The visual accommodation was the minimum focusing distance for each eye at which vision became blurred - 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. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 12 | 
| Change From Baseline in Visual Accommodation at Week 28: Study A0221109 | The visual accommodation was the minimum focusing distance for each eye at which vision became blurred - 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. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 28 | 
| Change From Baseline in Visual Accommodation at Final Visit: Study A0221109 | The visual accommodation was the minimum focusing distance for each eye at which vision became blurred - 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. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Final visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Child Behavior Checklist (CBCL) T Score (Derived Score) at Week 12: Study A0221109 | CBCL: assessed child's behavioral 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 categorized in 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 ADM tool raw scores transformed/derived into standard T-scores, range: each domain=50-100, internalizing problems=34-100, externalizing problems=33-100, total problems=24-100. Lower T-score (8 domain,2 summary,total problems)=better outcomes. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 12 | 
| Change From Baseline in Child Behavior Checklist (CBCL) T Score (Derived Score) at Week 28: Study A0221109 | CBCL: assessed child's behavioral 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 categorized in 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 ADM tool raw scores transformed/derived into standard T-scores, range: each domain=50-100, internalizing problems=34-100, externalizing problems=33-100, total problems=24-100. Lower T-score (8 domain,2 summary,total problems)=better outcomes. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 28 | 
| Change From Baseline in Child Behavior Checklist (CBCL) T Score (Derived Score) at Final Visit: Study A0221109 | CBCL: assessed child's behavioral 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 categorized in 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 ADM tool raw scores transformed/derived into standard T-scores, range: each domain=50-100, internalizing problems=34-100, externalizing problems=33-100, total problems=24-100. Lower T-score (8 domain,2 summary,total problems)=better outcomes. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Final visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Child Behavior Checklist (CBCL) Total Score (Raw Score) at Week 12: Study A0221109 | CBCL:assessed child's behavioral 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) =0-36; anxious/depressed,TSR=0-26; attention problems,TSR=0-20; rule-breaking behavior, TSR=0-34; social problems, TSR=0-22; somatic complaints, TSR=0-22; thought problems, TSR=0-30; withdrawn, TSR=0-16. Summary scores: externalizing problems combined rule-breaking and aggressive behavior,TSR=0-70; internalizing problems combined anxious/depressed, withdrawn and somatic complaints, TSR=0-64. Total problems combined 8 domains and 17 remaining items,TSR=0-240. TSR for each domain, summary and total problems was sum of scores of related items respectively. Lower scores for each domain, summary, total problems = better outcomes.Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 12 | 
| Change From Baseline in Child Behavior Checklist (CBCL) Total Score (Raw Score) at Week 28: Study A0221109 | CBCL:assessed child's behavioral 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) =0-36; anxious/depressed,TSR=0-26; attention problems,TSR=0-20; rule-breaking behavior, TSR=0-34; social problems, TSR=0-22; somatic complaints, TSR=0-22; thought problems, TSR=0-30; withdrawn, TSR=0-16. Summary scores: externalizing problems combined rule-breaking and aggressive behavior,TSR=0-70; internalizing problems combined anxious/depressed, withdrawn and somatic complaints, TSR=0-64. Total problems combined 8 domains and 17 remaining items,TSR=0-240. TSR for each domain, summary and total problems was sum of scores of related items respectively. Lower scores for each domain, summary, total problems = better outcomes.Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 28 | 
| Change From Baseline in Child Behavior Checklist (CBCL) Total Score (Raw Score) at Final Visit: Study A0221109 | CBCL:assessed child's behavioral 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) =0-36; anxious/depressed,TSR=0-26; attention problems,TSR=0-20; rule-breaking behavior, TSR=0-34; social problems, TSR=0-22; somatic complaints, TSR=0-22; thought problems, TSR=0-30; withdrawn, TSR=0-16. Summary scores: externalizing problems combined rule-breaking and aggressive behavior,TSR=0-70; internalizing problems combined anxious/depressed, withdrawn and somatic complaints, TSR=0-64. Total problems combined 8 domains and 17 remaining items,TSR=0-240. TSR for each domain, summary and total problems was sum of scores of related items respectively. Lower scores for each domain, summary, total problems = better outcomes.Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Final visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Grooved Pegboard Test (10 Pegs Group) at Week 12- Time to Completion: Study A0221109 | The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. Participants were asked to insert 10 grooved pegs into 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. Participants were assigned to either a 10 or 25-peg assessment based on their age. 10-peg assessment was done on participants below age of 9 years. In this outcome measure data for dominant and non-dominant hand have been reported separately. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 12 | 
| Change From Baseline in Grooved Pegboard Test (10 Pegs Group) at Week 28- Time to Completion: Study A0221109 | The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. Participants were asked to insert 10 grooved pegs into 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. Participants were assigned to either a 10 or 25-peg assessment based on their age. 10-peg assessment was done on participants below age of 9 years. In this outcome measure data for dominant and non-dominant hand have been reported separately. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 28 | 
| Change From Baseline in Grooved Pegboard Test (10 Pegs Group) at Final Visit- Time to Completion: Study A0221109 | The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. Participants were asked to insert 10 grooved pegs into 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. Participants were assigned to either a 10 or 25-peg assessment based on their age. 10-peg assessment was done on participants below age of 9 years. In this outcome measure data for dominant and non-dominant hand have been reported separately. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Final visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Grooved Pegboard Test (25 Pegs Group) at Week 12- Time to Completion: Study A0221109 | The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. Participants were asked to insert 25 grooved pegs into 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. Participants were assigned to either a 10 or 25-peg assessment based on their age. 25-peg assessment was done on participants of age 9 years and above. In this outcome measure data for dominant and non-dominant hand have been reported separately. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 12 | 
| Change From Baseline in Grooved Pegboard Test (25 Pegs Group) at Week 28- Time to Completion: Study A0221109 | The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. 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. Participants were assigned to either a 10 or 25-peg assessment based on their age. 25-peg assessment was done on participants of age 9 years and above. In this outcome measure data for dominant and non-dominant hand have been reported separately. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 28 | 
| Change From Baseline in Grooved Pegboard Test (25 Pegs Group) at Final Visit- Time to Completion: Study A0221109 | The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. 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. Participants were assigned to either a 10 or 25-peg assessment based on their age. 25-peg assessment was done on participants of age 9 years and above. In this outcome measure data for dominant and non-dominant hand have been reported separately. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Final visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Grooved Pegboard Test (10 Pegs Group) at Week 12- Number of Pegs Dropped: Study A0221109 | The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. 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. Number of pegs dropped while putting in the holes were measured. Participants were assigned to either a 10 or 25-peg assessment based on their age. 10-peg assessment was done on participants below age of 9 years. In this outcome measure data for dominant and non-dominant hand have been reported separately. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 12 | 
| Change From Baseline in Grooved Pegboard Test (10 Pegs Group) at Week 28- Number of Pegs Dropped: Study A0221109 | The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. 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. Number of pegs dropped while putting in the holes were measured. Participants were assigned to either a 10 or 25-peg assessment based on their age. 10-peg assessment was done on participants below age of 9 years. In this outcome measure data for dominant and non-dominant hand have been reported separately. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 28 | 
| Change From Baseline in Grooved Pegboard Test (10 Pegs Group) at Final Visit- Number of Pegs Dropped: Study A0221109 | The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. 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. Number of pegs dropped while putting in the holes were measured. Participants were assigned to either a 10 or 25-peg assessment based on their age. 10-peg assessment was done on participants below age of 9 years. In this outcome measure data for dominant and non-dominant hand have been reported separately. Data for this outcome measure was planned to be analyzed for each treatment group of Study A0221109 only. | A0221109: Baseline, final visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Grooved Pegboard Test (25 Pegs Group) at Week 12- Number of Pegs Dropped: Study A0221109 | The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. 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. Number of pegs dropped while putting in the holes were measured. Participants were assigned to either a 10 or 25-peg assessment based on their age. 25-peg assessment was done on participants of age 9 years and above. In this outcome measure data for dominant and non-dominant hand have been reported separately. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 12 | 
| Change From Baseline in Grooved Pegboard Test (25 Pegs Group) at Week 28- Number of Pegs Dropped: Study A0221109 | The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. 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. Number of pegs dropped while putting in the holes were measured. Participants were assigned to either a 10 or 25-peg assessment based on their age. 25-peg assessment was done on participants of age 9 years and above. In this outcome measure data for dominant and non-dominant hand have been reported separately. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 28 | 
| Change From Baseline in Grooved Pegboard Test (25 Pegs Group) at Final Visit- Number of Pegs Dropped: Study A0221109 | The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. 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. Number of pegs dropped while putting in the holes were measured. Participants were assigned to either a 10- or 25-peg assessment based on their age. 25-peg assessment was done on participants of age 9 years and above. In this outcome measure data for dominant and non-dominant hand have been reported separately. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Final visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Grooved Pegboard Test (10 Pegs Group) at Week 12- Number of Pegs Placed Correctly: Study A0221109 | The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. 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. Number of pegs placed correctly in hole was measured. Participants were assigned to either a 10 or 25-peg assessment based on their age. 10-peg assessment was done on participants below age of 9 years. In this outcome measure data for dominant and non-dominant hand have been reported separately. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 12 | 
| Change From Baseline in Grooved Pegboard Test (10 Pegs Group) at Week 28- Number of Pegs Placed Correctly: Study A0221109 | The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. 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. Number of pegs placed correctly in hole was measured. Participants were assigned to either a 10 or 25-peg assessment based on their age. 10-peg assessment was done on participants below age of 9 years. In this outcome measure data for dominant and non-dominant hand have been reported separately. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 28 | 
| Change From Baseline in Grooved Pegboard Test (10 Pegs Group) at Final Visit- Number of Pegs Placed Correctly: Study A0221109 | The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. 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. Number of pegs placed correctly in hole was measured. Participants were assigned to either a 10 or 25-peg assessment based on their age. 10-peg assessment was done on participants below age of 9 years. In this outcome measure data for dominant and non-dominant hand have been reported separately. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Final visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Grooved Pegboard Test (25 Pegs Group) at Week 12- Number of Pegs Placed Correctly: Study A0221109 | The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. 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. Number of pegs placed correctly in hole was measured. Participants were assigned to either a 10 or 25-peg assessment based on their age. 25-peg assessment was done on participants of age 9 years and above. In this outcome measure data for dominant and non-dominant hand have been reported separately. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 12 | 
| Change From Baseline in Grooved Pegboard Test (25 Pegs Group) at Week 28- Number of Pegs Placed Correctly: Study A0221109 | The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. 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. Number of pegs placed correctly in hole was measured. Participants were assigned to either a 10 or 25-peg assessment based on their age. 25-peg assessment was done on participants of age 9 years and above. In this outcome measure data for dominant and non-dominant hand have been reported separately. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 28 | 
| Change From Baseline in Grooved Pegboard Test (25 Pegs Group) at Final Visit- Number of Pegs Placed Correctly: Study A0221109 | The grooved pegboard test was a manipulative dexterity test that assessed psychomotor speed, fine motor control, and rapid-visual motor coordination. 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. Number of pegs placed correctly in hole was measured. Participants were assigned to either a 10 or 25-peg assessment based on their age. 25-peg assessment was done on participants of age 9 years and above. In this outcome measure data for dominant and non-dominant hand have been reported separately. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Final visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Vital Sign (Blood Pressure) at Week 12: Study A0221109 | Systolic and diastolic blood pressure were evaluated for examination of vital signs. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 12 | 
| Change From Baseline in Vital Sign (Blood Pressure) at Week 28: Study A0221109 | Systolic and diastolic blood pressure were evaluated for examination of vital signs. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 28 | 
| Change From Baseline in Vital Sign (Blood Pressure) at Final Visit: Study A0221109 | Systolic and diastolic blood pressure were evaluated for examination of vital signs. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Final visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Vital Sign (Pulse Rate) at Week 12: Study A0221109 | Pulse rate was evaluated for examination of vital signs. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 12 | 
| Change From Baseline in Vital Sign (Pulse Rate) at Week 28: Study A0221109 | Pulse rate was evaluated for examination of vital signs. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 28 | 
| Change From Baseline in Vital Sign (Pulse Rate) at Final Visit: Study A0221109 | Pulse rate was evaluated for examination of vital signs. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Final visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Number of Participants With Adverse Event Urinary Tract Infections (UTI): Merged Data of Studies A0221047 and A0221109 | UTI data were summarized for each cohort, each treatment group and the total of treatment groups, using the merged data of studies A0221047 and A0221109 as planned. | Up to a maximum of 56 weeks (24 weeks of treatment in A0221047 and 32 weeks [28 weeks treatment + 4 weeks follow up post last dose] in A0221109) | 
| Number of Participants With Clinical Laboratory Abnormalities | 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*UL; basophils, eosinophils, monocytes >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 <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, 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, glucose, ketones, protein, hemoglobin, nitrite, leukocyte esterase >=1; erythrocytes, leukocytes >=20; epithelial cells >=6, bacteria >20, hyaline casts >1. Data for this outcome was planned to be analysed for each treatment group of study A0221109 only. | A0221109: Baseline to 28 weeks | 
| Change From Baseline in Post-Void Residual (PVR) Volume at Week 12: Study A0221109 | Post-void residual volume was assessed by an ultrasound. PVR volume was assessed only in participants who did not perform clean intermittent catheterization or in any participants who had >1 UTI during the study. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 12 | 
| Change From Baseline in Post-Void Residual (PVR) Volume at Week 28: Study A0221109 | 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. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, Week 28 | 
| Change From Baseline in Post-Void Residual (PVR) Volume at Final Visit: Study A0221109 | 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. Data for this outcome measure was planned to be analyzed for each treatment group of study A0221109 only. | A0221109: Baseline, final visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Maximum Cystometric Bladder Capacity at Week 12 of Study A0221047 and at Week 28 and Final Visit of Study A0221109 | Maximum cystometric bladder capacity was defined as maximal tolerable cystometric capacity, until voiding or leaking begins or at a pressure of >=40 centimeter (cm) water (H2O). Maximum cystometric bladder capacity was summarized for each cohort, each treatment group and total of treatment groups, using the merged data of studies A0221047 and A0221109 as planned. | Study A0221047: Baseline, Week 12; Study A0221109: Week 28, Final Visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Detrusor Pressure at Maximum Bladder Capacity at Week 12 of Study A0221047 and at Week 28 and Final Visit of Study A0221109 | Detrusor pressure (cm H2O) at maximum urinary bladder capacity was measured using urodynamic testing. Detrusor pressure was summarized for each cohort, each treatment group and total of treatment groups, using the merged data of studies A0221047 and A0221109 as planned. | Study A0221047: Baseline, Week 12; Study A0221109: Week 28, Final Visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Number of Participants With Presence of Involuntary Detrusor Contraction (IDC) at Baseline and Week 12 of Study A0221047 and at Week 28 and Final Visit of Study A0221109 | Participants with presence of IDC was summarized for each cohort, each treatment group and total of treatment groups, using the merged data of studies A0221047 and A0221109 as planned. | Study A0221047: Baseline, Week 12; Study A0221109: Week 28, Final Visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Bladder Volume at First Involuntary Detrusor Contraction (IDC) at Week 12 of Study A0221047 and at Week 28 and Final Visit of Study A0221109 | Bladder volume at first IDC was measured using urodynamic testing. Bladder volume at first IDC was summarized for each cohort, each treatment group and total of treatment groups, using the merged data of studies A0221047 and A0221109 as planned. | Study A0221047: Baseline, Week 12; Study A0221109: Week 28, Final Visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Bladder Compliance at Week 12 of Study A0221047 and at Week 28 and Final Visit of Study A0221109 | 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). Bladder Compliance was summarized for each cohort, each treatment group and total of treatment groups, using the merged data of studies A0221047 and A0221109 as planned. | Study A0221047: Baseline, Week 12; Study A0221109: Week 28, Final Visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Mean Number of Micturitions Per 24 Hours at Week 12 of Study A0221047 and at Week 28 and Final Visit of Study A0221109 | 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. Data was summarized for each cohort, each treatment group and total of treatment groups, using the merged data of studies A0221047 and A0221109 as planned. | Study A0221047: Baseline, Week 12; Study A0221109: Week 28, Final Visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Mean Number of Catheterizations Per 24 Hours at Week 12 of Study A0221047 and at Week 28 and Final Visit of Study A0221109 | 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, even if it was not a full 24 hour period. This outcome measure was only calculated for participants with >0 catheterizations at Baseline. Data was summarized for each cohort, each treatment group and total of treatment groups, using the merged data of studies A0221047 and A0221109 as planned. | Study A0221047: Baseline, Week 12; Study A0221109: Week 28, Final Visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Mean Number of Micturitions or Catheterizations Combined Per 24 Hours at Week 12 of Study A0221047 and at Week 28 and Final Visit of Study A0221109 | The mean number of micturitions and 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 (hr) period. This outcome measure was only calculated for participants with >0 micturitions or catheterizations at Baseline. Data was summarized for each cohort, each treatment group and total of treatment groups, using the merged data of studies A0221047 and A0221109 as planned. | Study A0221047: Baseline, Week 12; Study A0221109: Week 28, Final Visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Mean Number of Incontinence Episodes Per 24 Hours at Week 12 of Study A0221047 and at Week 28 and Final Visit of Study A0221109 | 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 hour period. This outcome measure was only calculated for participants with >0 incontinence episodes at Baseline. Data was summarized for each cohort, each treatment group and total of treatment groups, using the merged data of studies A0221047 and A0221109 as planned. | Study A0221047: Baseline, Week 12; Study A0221109: Week 28, Final Visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Mean Number of Urgency Episodes Per 24 Hours at Week 12 of Study A0221047 and at Week 28 and Final Visit of Study A0221109 | 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 hour period. Urgency episodes were defined as urgency marked as 'yes' in the diary. This outcome measure was only calculated for sensate participants with >0 urgency episodes at Baseline. Data was summarized for each cohort, each treatment group and total of treatment groups, using the merged data of studies A0221047 and A0221109 as planned. | Study A0221047: Baseline, Week 12; Study A0221109: Week 28, Final Visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Mean Volume Voided Per Micturition at Week 12 of Study A0221047 and at Week 28 and Final Visit of Study A0221109 | 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 >0. This outcome measure included only participants who actually had the records of volume voided per micturition. Data was summarized for each cohort, each treatment group and total of treatment groups, using the merged data of studies A0221047 and A0221109 as planned. | Study A0221047: Baseline, Week 12; Study A0221109: Week 28, Final Visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Mean Volume Voided Per Catheterization at Week 12 of Study A0221047 and at Week 28 and Final Visit of Study A0221109 | The mean volume per catheterization was calculated as sum of voided volume divided by the total number of catheterization, with a recorded voided volume >0. This outcome measure included only participants who actually had the records of volume voided per catherization. Data was summarized for each cohort, each treatment group and total of treatment groups, using the merged data of studies A0221047 and A0221109 as planned. | Study A0221047: Baseline, Week 12; Study A0221109: Week 28, Final Visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 
| Change From Baseline in Mean Volume Voided Per Micturition or Catheterization at Week 12 of Study A0221047 and at Week 28 and Final Visit of Study A0221109 | 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 >0. Data was summarized for each cohort, each treatment group and total of treatment groups, using the merged data of studies A0221047 and A0221109 as planned. | Study A0221047: Baseline, Week 12; Study A0221109: Week 28, Final Visit (Week 28 for participants who completed the study or in case of early withdrawal the last assessment before Week 28 was considered to be the final visit) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neurogenic detrusor overactivity, fesoterodine, Japan