Clinical trial NCT01565707: A Study to Investigate How Effective and Safe Solifenacin Succinate Suspension is in Treating Children/Adolescents Aged 5 to Less Than 18 Years With Symptoms of Overactive Bladder (OAB) Compared to a Non-active Drug
Official title: A Phase 3, Double-Blind, Randomized, Multi-center, Placebo-Controlled Sequential Dose Titration Study to Assess Efficacy, Safety and Population Pharmacokinetics of Solifenacin Succinate Suspension in Pediatric Subjects From 5 to Less Than 18 Years of Age With Overactive Bladder (OAB)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Urinary Bladder, Overactive
Keywords: Pediatric
Solifenacin succinate suspension
Phase 3
Pharmacokinetics
Overactive bladder (OAB)
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2012-03-29
Enrollment: 189
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Solifenacin succinate as a tablet formulation is already on the market for the treatment of symptoms of overactive bladder in adults. For the use in children and adolescent patients a new formulation of solifenacin has been developed.

This study investigated the effect and safety of solifenacin succinate liquid suspension compared to a non-active drug (placebo) over a 12-week period. The 2 weeks prior to the double blind period was a single-blind placebo run-in period in combination with behavioral urotherapy (Non-interventional diary assisted urotherapy consisting of overactive bladder (OAB) information, awareness, instruction, life-style advice and documentation of voiding habits and symptoms for OAB), followed by a 12 week daily treatment period. The study also investigated how well solifenacin succinate suspension is taken-up by the body and how long it stays in the body during this time.


Eligibility criteria: Main Inclusion Criteria:

* Written Informed Consent has been obtained
* OAB (symptoms of urgency) according to International Children's Continence Society (ICCS) criteria
* Daytime incontinence with at least 4 or more episodes of incontinence confirmed by 7 day participant diary

Main Exclusion Criteria:

* Daily voiding frequency less than 5
* Extraordinary daytime urinary frequency according to the International Children's Continence Society (ICCS) definition
* Uroflow indicative of pathology other than OAB
* Maximum voided volume (morning volume excluded) \> expected bladder capacity for age \[(age +1) x 30\] in ml or a maximum voided volume (morning volume excluded) above 390 ml
* Post Void Residual (PVR) \> 20 ml
* Monosymptomatic enuresis
* Polyuria defined as \> 75 ml/kg/b.w./24 hours
* Dysfunctional voiding
* Congenital anomalies affecting lower urinary tract function
* Current constipation
* Current Urinary Tract Infection (UTI)
* Catheterization within 2 weeks prior to screening

Primary outcomes:
measure: Change From Baseline to End of Treatment (EoT) in Mean Volume Voided (MVV) Per Micturition
timeFrame: Baseline and Week 12
Secondary outcomes:
measure: Change From Baseline to End of Treatment in Daytime Maximum Volume Voided (DMaxVV) Per Micturition
timeFrame: Baseline and Week 12
measure: Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours
timeFrame: Baseline and Week 12
measure: Change From Baseline to End of Treatment in Mean Number of Daytime Incontinence Episodes Per 24 Hours
timeFrame: Baseline and Week 12
measure: Change From Baseline to End of Treatment in Mean Number of Nighttime Incontinence Episodes Per 24 Hours
timeFrame: Baseline and Week 12
measure: Change From Baseline to End of Treatment in Mean Number of Dry (Incontinence-Free) Days Per 7 Days
timeFrame: Baseline and Week 12
measure: Change From Baseline to End of Treatment in Mean Number of Dry (Incontinence-Free) Nighttimes Per 7 Days
timeFrame: Baseline and Week 12
measure: Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours
timeFrame: Baseline and Week 12
measure: Change From Baseline to End of Treatment in Mean Number of Daytime Micturitions Per 24 Hours
timeFrame: Baseline and week 12
measure: Change From Baseline to End of Treatment in Mean Number of Nighttime Micturitions Per 24 Hours
timeFrame: Baseline and Week 12
measure: Change From Baseline to End of Treatment in Mean Number of Grade 3 or 4 Urgency Episodes Per 24 Hours in Adolescents
timeFrame: Baseline and Week 12
measure: Maximum Concentration (Cmax) of Solifenacin
timeFrame: Week 12/Day 84 (within 3 hours before dosing, 1-3 hours, 4-5 hours, 7-10 hours after dosing) and one sample at Visit 8/Day 87 (2-3 days after last dose intake).
measure: Time to Attain Maximum Concentration (Tmax) of Solifenacin
timeFrame: Week 12/Day 84 (within 3 hours before dosing, 1-3 hours, 4-5 hours, 7-10 hours after dosing) and one sample at Visit 8/Day 87 (2-3 days after last dose intake).
measure: Plasma Concentration Before Drug Administration (Ctrough) of Solifenacin
timeFrame: Week 12/Day 84 (within 3 hours before dosing, 1-3 hours, 4-5 hours, 7-10 hours after dosing) and one sample at Visit 8/Day 87 (2-3 days after last dose intake).
measure: Area Under the Plasma Concentration - Time to Curve (AUC) for a Dose Interval (AUCtau) of Solifenacin
timeFrame: Week 12/Day 84 (within 3 hours before dosing, 1-3 hours, 4-5 hours, 7-10 hours after dosing) and one sample at Visit 8/Day 87 (2-3 days after last dose intake).
measure: Apparent Terminal Elimination Half-Life (T1/2) of Solifenacin
timeFrame: Week 12/Day 84 (within 3 hours before dosing, 1-3 hours, 4-5 hours, 7-10 hours after dosing) and one sample at Visit 8/Day 87 (2-3 days after last dose intake).
measure: Apparent Total Body Clearance (CL/F) of Solifenacin
timeFrame: Week 12/Day 84 (within 3 hours before dosing, 1-3 hours, 4-5 hours, 7-10 hours after dosing) and one sample at Visit 8/Day 87 (2-3 days after last dose intake).
measure: Apparent Volume of Distribution (Vz/F) of Solifenacin
timeFrame: Week 12/Day 84 (within 3 hours before dosing, 1-3 hours, 4-5 hours, 7-10 hours after dosing) and one sample at Visit 8/Day 87 (2-3 days after last dose intake).
measure: Number of Participants With Adverse Events (AEs)
timeFrame: From the first dose of study drug until 7 days after last dose of study medication (13 weeks).
measure: Change From Baseline in Post Void Residual (PVR) Volume
timeFrame: Baseline and Week 12
Other outcomes:
Locations:
city: Shreveport
country: United States
facility: Site: 1006
state: Louisiana
city: Albany
country: United States
facility: Site: 1015
state: New York
city: Antwerp
country: Belgium
facility: Site: 3202
city: Antwerp
country: Belgium
facility: Site: 3209
city: Charleroi
country: Belgium
facility: Site: 3208
city: Gent
country: Belgium
facility: Site: 3201
city: Gent
country: Belgium
facility: Site: 3203
city: Kortrijk
country: Belgium
facility: Site: 3204
city: Leuven
country: Belgium
facility: Site: 3205
city: Campinas
country: Brazil
facility: Site: 5507
city: Curitiba
country: Brazil
facility: Site: 5506
city: Hamilton
country: Canada
facility: Site: 1005
city: Quebec
country: Canada
facility: Site: 1001
city: Aalborg
country: Denmark
facility: Site: 4503
city: Aarhus N
country: Denmark
facility: Site: 4501
city: Koge
country: Denmark
facility: Site: 4504
city: Kolding
country: Denmark
facility: Site: 4502
city: Belgrade
country: Former Serbia and Montenegro
facility: Site: 3810
city: Novi Sad
country: Former Serbia and Montenegro
facility: Site: 3812
city: Daegu
country: Korea, Republic of
facility: Site:8203
city: Incheon
country: Korea, Republic of
facility: Site: 8206
city: Seoul
country: Korea, Republic of
facility: Site: 8207
city: Seoul
country: Korea, Republic of
facility: Site: 8201
city: Seoul
country: Korea, Republic of
facility: Site:8202
city: Mexico City
country: Mexico
facility: Site: 5202
city: Mexico City
country: Mexico
facility: Site: 5205
city: Bergen
country: Norway
facility: Site: 4701
city: Trondheim
country: Norway
facility: Site: 4702
city: Quezon City
country: Philippines
facility: Site: 6301
city: Gdansk
country: Poland
facility: Site: 4805
city: Gdansk
country: Poland
facility: Site: 4803
city: Lubin
country: Poland
facility: Site: 4804
city: Warsaw
country: Poland
facility: Site: 4801
city: Cape Town
country: South Africa
facility: Site: 2703
city: Gothenburg
country: Sweden
facility: Site: 4606
city: Jonkoping
country: Sweden
facility: Site: 4601
city: Skovde
country: Sweden
facility: Site: 4603
city: Stockholm
country: Sweden
facility: Site: 4602
city: Umea
country: Sweden
facility: Site: 4605
city: Ankara
country: Turkey
facility: Site: 9001
city: Izmir
country: Turkey
facility: Site: 9002
city: Dnipropetrovsk
country: Ukraine
facility: Site: 3853
city: Kharkiv
country: Ukraine
facility: Site: 3854
city: Kiev
country: Ukraine
facility: Site: 3850
city: Leeds
country: United Kingdom
facility: Site: 4403
city: Sheffield
country: United Kingdom
facility: Site: 4401
Study officials:
affiliation: Astellas Pharma Europe B.V.
name: Clinical Study Manager
role: STUDY_CHAIR
References:
citation: Tannenbaum S, den Adel M, Krauwinkel W, Meijer J, Hollestein-Havelaar A, Verheggen F, Newgreen D. Pharmacokinetics of solifenacin in pediatric populations with overactive bladder or neurogenic detrusor overactivity. Pharmacol Res Perspect. 2020 Dec;8(6):e00684. doi: 10.1002/prp2.684.
citation: Snijder R, Bosman B, Stroosma O, Agema M. Relationship between mean volume voided and incontinence in children with overactive bladder treated with solifenacin: post hoc analysis of a phase 3 randomised clinical trial. Eur J Pediatr. 2020 Oct;179(10):1523-1528. doi: 10.1007/s00431-020-03635-2. Epub 2020 Apr 1.
citation: Newgreen D, Bosman B, Hollestein-Havelaar A, Dahler E, Besuyen R, Sawyer W, Bolduc S, Rittig S. Solifenacin in Children and Adolescents with Overactive Bladder: Results of a Phase 3 Randomised Clinical Trial. Eur Urol. 2017 Mar;71(3):483-490. doi: 10.1016/j.eururo.2016.08.061. Epub 2016 Sep 28.