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
- Conditions
- Urinary Bladder, Overactive
- Interventions
- Registration Number
- NCT01565707
- Lead Sponsor
- Astellas Pharma Europe B.V.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 189
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Children Placebo Children aged 5 to 11 years received matching placebo suspension once a day for 12 weeks. Placebo Children Urotherapy Children aged 5 to 11 years received matching placebo suspension once a day for 12 weeks. Solifenacin Succinate Suspension Children Urotherapy Children aged 5 to 11 years received solifenacin succinate suspension once a day for 12 weeks. The initial dose started with pediatric equivalent dose (PED) of 5 mg (PED5) based on weight and was titrated up or down to reach the optimal dose. The minimum dose was PED2.5, and the maximum dose was PED10. Placebo Adolescents Placebo Adolescents aged 12 to 17 years received matching placebo suspension once a day for 12 weeks. Placebo Adolescents Urotherapy Adolescents aged 12 to 17 years received matching placebo suspension once a day for 12 weeks. Solifenacin Succinate Suspension Adolescents Urotherapy Adolescents aged 12 to 17 years received solifenacin succinate suspension once a day for 12 weeks. The initial dose started with pediatric equivalent dose (PED) of 5 mg (PED5) based on weight and was titrated up or down to reach the optimal dose. The minimum dose was PED2.5, and the maximum dose was PED10. Solifenacin Succinate Suspension Children Solifenacin Succinate Suspension Children aged 5 to 11 years received solifenacin succinate suspension once a day for 12 weeks. The initial dose started with pediatric equivalent dose (PED) of 5 mg (PED5) based on weight and was titrated up or down to reach the optimal dose. The minimum dose was PED2.5, and the maximum dose was PED10. Solifenacin Succinate Suspension Adolescents Solifenacin Succinate Suspension Adolescents aged 12 to 17 years received solifenacin succinate suspension once a day for 12 weeks. The initial dose started with pediatric equivalent dose (PED) of 5 mg (PED5) based on weight and was titrated up or down to reach the optimal dose. The minimum dose was PED2.5, and the maximum dose was PED10.
- Primary Outcome Measures
Name Time Method Change From Baseline to End of Treatment (EoT) in Mean Volume Voided (MVV) Per Micturition Baseline and Week 12 The mean voided volume was calculated from the participant diary data recorded during two measuring days (i.e., those days when the participant recorded the volume of each micturition) in the 7 days prior to the baseline and end of treatment visits. The MVV is equal to the mean of the non-zero volumes recorded over the 2 measuring days. A micturition is any voluntary urination, excluding episodes of incontinence.
- Secondary Outcome Measures
Name Time Method Change From Baseline to End of Treatment in Mean Number of Dry (Incontinence-Free) Days Per 7 Days Baseline and Week 12 The mean number of dry days was determined using the patient diary data recorded by the participant in the 7 days prior to baseline visit and end of treatment visit. An incontinence episode is defined as an episode with any involuntary loss of urine.
Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours Baseline and Week 12 An incontinence episode is defined as an episode with any involuntary loss of urine. The mean number of incontinence episodes was determined using the patient diary data recorded by the participant in the 7 days prior to baseline visit and end of treatment visit.
Change From Baseline to End of Treatment in Mean Number of Daytime Incontinence Episodes Per 24 Hours Baseline and Week 12 The mean number of incontinence episodes was determined using the patient diary data recorded by the participant in the 7 days prior to baseline visit and end of treatment visit. An incontinence episode is defined as an episode with any involuntary loss of urine. Daytime is defined as the time between waking up in the morning and going to bed later the same day.
Change From Baseline to End of Treatment in Mean Number of Nighttime Incontinence Episodes Per 24 Hours Baseline and Week 12 The mean number of incontinence episodes was determined using the patient diary data recorded by the participant in the 7 days prior to baseline visit and end of treatment visit. An incontinence episode is defined as an episode with any involuntary loss of urine. Nighttime is defined as the time between going to bed and waking up the following morning.
Change From Baseline to End of Treatment in Daytime Maximum Volume Voided (DMaxVV) Per Micturition Baseline and Week 12 The mean daytime maximum volume voided (DMaxVV) was determined using the participant diary data recorded during two measuring days (i.e., those days when the participant recorded the volume of each micturition) in the 7 days prior to the Baseline and end of treatment visits. The daytime maximum volume voided (DMaxVV) is the largest (non-zero) volume recorded over both of the 2 measuring days in the diary. The first morning void is excluded from the calculation. Daytime is defined as the time between waking up in the morning and going to bed later the same day. A micturition is any voluntary urination, excluding episodes of incontinence.
Change From Baseline to End of Treatment in Mean Number of Dry (Incontinence-Free) Nighttimes Per 7 Days Baseline and Week 12 The mean number of dry nights was determined using the patient diary data recorded by the participant in the 7 days prior to baseline visit and end of treatment visit. An incontinence episode is defined as an episode with any involuntary loss of urine.
Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours Baseline and Week 12 The mean number of micturitions was determined using the patient diary data recorded by the participant in the 7 days prior to baseline visit and end of treatment visit. A micturition is any voluntary urination, excluding episodes of incontinence.
Apparent Terminal Elimination Half-Life (T1/2) of Solifenacin 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). Pharmacokinetic sampling was performed at steady state at the end of treatment.
Number of Participants With Adverse Events (AEs) From the first dose of study drug until 7 days after last dose of study medication (13 weeks). A treatment emergent adverse event (TEAE) was defined as an AE that occurred after the first dose of study drug and within 7 days after last dose of study medication.
Change From Baseline to End of Treatment in Mean Number of Daytime Micturitions Per 24 Hours Baseline and week 12 The mean number of micturitions was determined using the patient diary data recorded by the participant in the 7 days prior to baseline visit and end of treatment visit. A micturition is any voluntary urination, excluding episodes of incontinence. Daytime is defined as the time between waking up in the morning and going to bed later the same day.
Change From Baseline in Post Void Residual (PVR) Volume Baseline and Week 12 Post Void Residual (PVR) Volume was assessed by ultrasonography or bladder scan.
Change From Baseline to End of Treatment in Mean Number of Grade 3 or 4 Urgency Episodes Per 24 Hours in Adolescents Baseline and Week 12 Adolescent participants were asked to record the degree of urgency associated with each micturition and incontinence episode according to the Patient Perception of Intensity of Urgency Scale (PPIUS) scale (0 - no urgency, 1 - mild urgency, 2 - moderate urgency, 3 - severe urgency, 4 - urge incontinence). The mean number of grade 3 or 4 urgency episodes was determined using using diary data recorded by the participant in the 7 days prior to baseline visit and end of treatment visit.
Maximum Concentration (Cmax) of Solifenacin 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). Pharmacokinetic sampling was performed at steady state at the end of treatment. Cmax could not be calculated for 2 children and 1 adolescent in the Pharmacokinetic Analysis Set (PKAS).
Change From Baseline to End of Treatment in Mean Number of Nighttime Micturitions Per 24 Hours Baseline and Week 12 The mean number of micturitions was determined using the patient diary data recorded by the participant in the 7 days prior to baseline visit and end of treatment visit. A micturition is any voluntary urination, excluding episodes of incontinence. Nighttime is defined as the time between going to bed and waking up the following morning.
Time to Attain Maximum Concentration (Tmax) of Solifenacin 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). Pharmacokinetic sampling was performed at steady state at the end of treatment. Tmax could not be calculated for 2 children and 1 adolescent in the PKAS.
Plasma Concentration Before Drug Administration (Ctrough) of Solifenacin 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). Pharmacokinetic sampling was performed at steady state at the end of treatment. Ctrough could not be calculated for 2 children and 1 adolescent in the PKAS.
Area Under the Plasma Concentration - Time to Curve (AUC) for a Dose Interval (AUCtau) of Solifenacin 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). Pharmacokinetic sampling was performed at steady state at the end of treatment.
Apparent Total Body Clearance (CL/F) of Solifenacin 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). Pharmacokinetic sampling was performed at steady state at the end of treatment.
Apparent Volume of Distribution (Vz/F) of Solifenacin 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). Pharmacokinetic sampling was performed at steady state at the end of treatment.
Trial Locations
- Locations (46)
Site: 3853
🇺🇦Dnipropetrovsk, Ukraine
Site: 3854
🇺🇦Kharkiv, Ukraine
Site: 4502
🇩🇰Kolding, Denmark
Site: 4501
🇩🇰Aarhus N, Denmark
Site: 1015
🇺🇸Albany, New York, United States
Site: 5506
🇧🇷Curitiba, Brazil
Site: 3208
🇧🇪Charleroi, Belgium
Site: 1006
🇺🇸Shreveport, Louisiana, United States
Site:8203
🇰🇷Daegu, Korea, Republic of
Site: 3202
🇧🇪Antwerp, Belgium
Site: 3201
🇧🇪Gent, Belgium
Site: 3203
🇧🇪Gent, Belgium
Site: 1001
🇨🇦Quebec, Canada
Site: 3810
Belgrade, Former Serbia and Montenegro
Site: 3812
Novi Sad, Former Serbia and Montenegro
Site: 4504
🇩🇰Koge, Denmark
Site: 4503
🇩🇰Aalborg, Denmark
Site: 3209
🇧🇪Antwerp, Belgium
Site: 5507
🇧🇷Campinas, Brazil
Site: 3204
🇧🇪Kortrijk, Belgium
Site: 3205
🇧🇪Leuven, Belgium
Site: 1005
🇨🇦Hamilton, Canada
Site: 5202
🇲🇽Mexico City, Mexico
Site: 4701
🇳🇴Bergen, Norway
Site: 8207
🇰🇷Seoul, Korea, Republic of
Site:8202
🇰🇷Seoul, Korea, Republic of
Site: 8201
🇰🇷Seoul, Korea, Republic of
Site: 4606
🇸🇪Gothenburg, Sweden
Site: 4605
🇸🇪Umea, Sweden
Site: 4801
🇵🇱Warsaw, Poland
Site: 2703
🇿🇦Cape Town, South Africa
Site: 4601
🇸🇪Jonkoping, Sweden
Site: 8206
🇰🇷Incheon, Korea, Republic of
Site: 6301
🇵🇭Quezon City, Philippines
Site: 4702
🇳🇴Trondheim, Norway
Site: 4803
🇵🇱Gdansk, Poland
Site: 4805
🇵🇱Gdansk, Poland
Site: 4804
🇵🇱Lubin, Poland
Site: 4602
🇸🇪Stockholm, Sweden
Site: 4603
🇸🇪Skovde, Sweden
Site: 9001
🇹🇷Ankara, Turkey
Site: 9002
🇹🇷Izmir, Turkey
Site: 3850
🇺🇦Kiev, Ukraine
Site: 4403
🇬🇧Leeds, United Kingdom
Site: 4401
🇬🇧Sheffield, United Kingdom
Site: 5205
🇲🇽Mexico City, Mexico