Urinary Bladder, Overactive
Conditions
Keywords
Pediatric, Solifenacin succinate suspension, Phase 3, Pharmacokinetics, Overactive bladder (OAB)
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.
Interventions
Children aged 5 to 11 years and adolescents aged 12 to 17 years received solifenacin succinate liquid suspension once a day orally via syringe for 12 weeks along with 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. The initial dose started with the equivalent of 5 mg in adults, referred to as pediatric equivalent dose (PED) of 5 mg (PED5), based on body weight for three weeks and was titrated up or down in up to three titration steps of three weeks each to reach the optimal dose. Titration up or down could lead to weight-based doses equivalent to doses in adults of 2.5 mg, 5 mg, 7.5 mg or 10 mg once daily and were referred to as PED2.5, PED5, PED7.5 and PED10. The minimum dose was PED2.5, and the maximum dose was PED10. The decision to titrate up or down was made by the investigator using information from the 7 day patient diary.
DRUGPlacebo
Children aged 5 to 11 years and adolescents aged 12 to 17 years received matching placebo liquid suspension once a day orally via syringe for 12 weeks along with 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. The initial dose started with the equivalent of 5 mg in adults, referred to as pediatric equivalent dose (PED) of 5 mg (PED5), based on body weight for three weeks and was titrated up or down in up to three titration steps of three weeks each to reach the optimal dose. Titration up or down could lead to weight-based doses equivalent to doses in adults of 2.5 mg, 5 mg, 7.5 mg or 10 mg once daily and were referred to as PED2.5, PED5, PED7.5 and PED10. The minimum dose was PED2.5, and the maximum dose was PED10. The decision to titrate up or down was made by the investigator using information from the 7 day patient diary.
BEHAVIORALUrotherapy
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.
Sponsors
Astellas Pharma Europe B.V.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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. |
| 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 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. |
| 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. |
| 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. |
| 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 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. |
| 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. |
| 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 in Post Void Residual (PVR) Volume | Baseline and Week 12 | Post Void Residual (PVR) Volume was assessed by ultrasonography or bladder scan. |
| 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). |
Countries
Belgium, Brazil, Canada, Denmark, Mexico, Norway, Philippines, Poland, Serbia and Montenegro, South Africa, South Korea, Sweden, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
The study population consisted of male and female children (5 to 11 years old) and adolescents (12 to 17 years old) with overactive bladder (OAB).
Pre-assignment details
Subjects received 4 weeks of urotherapy (standard first line therapy for pediatric OAB patients). Two weeks after start of urotherapy a single-blind 2-week placebo run-in period began. After run-in period eligible subjects were randomized to 12 weeks of double-blind treatment (solifenacin succinate suspension or placebo) and continued urotherapy.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Children Children aged 5 to 11 years received matching placebo suspension once a day for 12 weeks. | 73 |
| Solifenacin Succinate Suspension Children 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. | 73 |
| Placebo Adolescents Adolescents aged 12 to 17 years received matching placebo suspension once a day for 12 weeks. | 19 |
| Solifenacin Succinate Suspension Adolescents 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. | 22 |
| Total | 187 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 6 | 2 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
| Overall Study | Miscellaneous | 1 | 1 | 0 | 2 |
| Overall Study | Protocol Violation | 1 | 0 | 0 | 1 |
| Overall Study | Randomized but not evaluable | 2 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo Children | Solifenacin Succinate Suspension Children | Placebo Adolescents | Solifenacin Succinate Suspension Adolescents | Total |
|---|---|---|---|---|---|
| Age, Continuous Adolescents | NA years | NA years | 14.4 years STANDARD_DEVIATION 1.9 | 14.2 years STANDARD_DEVIATION 1.8 | 14.3 years STANDARD_DEVIATION 1.8 |
| Age, Continuous Children | 7.4 years STANDARD_DEVIATION 1.6 | 7.6 years STANDARD_DEVIATION 1.6 | NA years | NA years | 7.5 years STANDARD_DEVIATION 1.6 |
| Daytime Maximum Volume Voided (DMaxVV) Per Micturition Adolescents | NA mL | NA mL | 278.16 mL STANDARD_DEVIATION 119.21 | 252.38 mL STANDARD_DEVIATION 108.68 | 264.63 mL STANDARD_DEVIATION 113.08 |
| Daytime Maximum Volume Voided (DMaxVV) Per Micturition Children | 141.43 mL STANDARD_DEVIATION 52.09 | 155.51 mL STANDARD_DEVIATION 70.66 | NA mL | NA mL | 148.62 mL STANDARD_DEVIATION 62.45 |
| Ethnicity Hispanic or Latino | 8 Participants | 9 Participants | 3 Participants | 2 Participants | 22 Participants |
| Ethnicity Not Hispanic or Latino | 65 Participants | 64 Participants | 16 Participants | 20 Participants | 165 Participants |
| Mean Number of Daytime Incontinence Episodes per 24 Hours Adolescents | NA daytime incontinence episodes | NA daytime incontinence episodes | 2.03 daytime incontinence episodes STANDARD_DEVIATION 2.18 | 1.50 daytime incontinence episodes STANDARD_DEVIATION 1.44 | 1.75 daytime incontinence episodes STANDARD_DEVIATION 1.83 |
| Mean Number of Daytime Incontinence Episodes per 24 Hours Children | 2.54 daytime incontinence episodes STANDARD_DEVIATION 2.75 | 1.98 daytime incontinence episodes STANDARD_DEVIATION 3.24 | NA daytime incontinence episodes | NA daytime incontinence episodes | 2.26 daytime incontinence episodes STANDARD_DEVIATION 3.01 |
| Mean Number of Daytime Micturitions per 24 Hours Adolescents | NA daytime micturitions | NA daytime micturitions | 6.79 daytime micturitions STANDARD_DEVIATION 2.92 | 6.88 daytime micturitions STANDARD_DEVIATION 2.14 | 6.84 daytime micturitions STANDARD_DEVIATION 2.51 |
| Mean Number of Daytime Micturitions per 24 Hours Children | 7.54 daytime micturitions STANDARD_DEVIATION 3.14 | 8.00 daytime micturitions STANDARD_DEVIATION 3.4 | NA daytime micturitions | NA daytime micturitions | 7.77 daytime micturitions STANDARD_DEVIATION 3.27 |
| Mean Number of Grade 3 or 4 Urgency Episodes per 24 Hours in Adolescents | NA urgency episodes | NA urgency episodes | 3.67 urgency episodes STANDARD_DEVIATION 4.15 | 2.42 urgency episodes STANDARD_DEVIATION 2.13 | 3.03 urgency episodes STANDARD_DEVIATION 3.29 |
| Mean Number of Incontinence Episodes per 24 Hours Adolescents | NA incontinence episodes | NA incontinence episodes | 2.81 incontinence episodes STANDARD_DEVIATION 2.45 | 1.82 incontinence episodes STANDARD_DEVIATION 1.66 | 2.29 incontinence episodes STANDARD_DEVIATION 2.11 |
| Mean Number of Incontinence Episodes per 24 Hours Children | 2.98 incontinence episodes STANDARD_DEVIATION 2.63 | 2.46 incontinence episodes STANDARD_DEVIATION 2.57 | NA incontinence episodes | NA incontinence episodes | 2.71 incontinence episodes STANDARD_DEVIATION 2.6 |
| Mean Number of Micturitions per 24 Hours Adolescents | NA micturitions | NA micturitions | 8.08 micturitions STANDARD_DEVIATION 3.82 | 7.52 micturitions STANDARD_DEVIATION 2.37 | 7.79 micturitions STANDARD_DEVIATION 3.11 |
| Mean Number of Micturitions per 24 Hours Children | 8.26 micturitions STANDARD_DEVIATION 2.56 | 8.27 micturitions STANDARD_DEVIATION 3.01 | NA micturitions | NA micturitions | 8.27 micturitions STANDARD_DEVIATION 2.79 |
| Mean Number of Nighttime Incontinence Episodes per 24 Hours Adolescents | NA nighttime incontinence episodes | NA nighttime incontinence episodes | 0.39 nighttime incontinence episodes STANDARD_DEVIATION 0.66 | 0.33 nighttime incontinence episodes STANDARD_DEVIATION 0.4 | 0.36 nighttime incontinence episodes STANDARD_DEVIATION 0.53 |
| Mean Number of Nighttime Incontinence Episodes per 24 Hours Children | 0.59 nighttime incontinence episodes STANDARD_DEVIATION 0.47 | 0.70 nighttime incontinence episodes STANDARD_DEVIATION 0.82 | NA nighttime incontinence episodes | NA nighttime incontinence episodes | 0.64 nighttime incontinence episodes STANDARD_DEVIATION 0.67 |
| Mean Number of Nighttime Micturitions per 24 Hours Adolescents | NA nighttime micturitions | NA nighttime micturitions | 0.61 nighttime micturitions STANDARD_DEVIATION 1.09 | 0.26 nighttime micturitions STANDARD_DEVIATION 0.41 | 0.43 nighttime micturitions STANDARD_DEVIATION 0.81 |
| Mean Number of Nighttime Micturitions per 24 Hours Children | 0.60 nighttime micturitions STANDARD_DEVIATION 0.78 | 0.56 nighttime micturitions STANDARD_DEVIATION 0.98 | NA nighttime micturitions | NA nighttime micturitions | 0.58 nighttime micturitions STANDARD_DEVIATION 0.88 |
| Mean Volume Voided (MVV) per Micturition Adolescents | NA mL | NA mL | 169.06 mL STANDARD_DEVIATION 63.65 | 159.55 mL STANDARD_DEVIATION 61.21 | 164.07 mL STANDARD_DEVIATION 61.76 |
| Mean Volume Voided (MVV) per Micturition Children | 94.06 mL STANDARD_DEVIATION 38.12 | 96.88 mL STANDARD_DEVIATION 40.98 | NA mL | NA mL | 95.50 mL STANDARD_DEVIATION 39.5 |
| Number of Dry (Incontinence-free) Days per 7 Days Adolescents | NA Dry Days | NA Dry Days | 1.0 Dry Days STANDARD_DEVIATION 1 | 1.5 Dry Days STANDARD_DEVIATION 1.3 | 1.3 Dry Days STANDARD_DEVIATION 1.2 |
| Number of Dry (Incontinence-free) Days per 7 Days Children | 0.5 Dry Days STANDARD_DEVIATION 0.9 | 0.9 Dry Days STANDARD_DEVIATION 1.6 | NA Dry Days | NA Dry Days | 0.7 Dry Days STANDARD_DEVIATION 1.3 |
| Number of Dry (Incontinence-free) Nights per 7 Days Adolescents | NA Dry Nights | NA Dry Nights | 5.6 Dry Nights STANDARD_DEVIATION 2.2 | 5.4 Dry Nights STANDARD_DEVIATION 2.2 | 5.5 Dry Nights STANDARD_DEVIATION 2.2 |
| Number of Dry (Incontinence-free) Nights per 7 Days Children | 3.4 Dry Nights STANDARD_DEVIATION 3 | 3.1 Dry Nights STANDARD_DEVIATION 3 | NA Dry Nights | NA Dry Nights | 3.2 Dry Nights STANDARD_DEVIATION 3 |
| Race American Indian/Alaskan Native | 3 Participants | 4 Participants | 2 Participants | 0 Participants | 9 Participants |
| Race Asian | 6 Participants | 5 Participants | 3 Participants | 4 Participants | 18 Participants |
| Race Black/African American | 3 Participants | 2 Participants | 1 Participants | 2 Participants | 8 Participants |
| Race Other | 4 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants |
| Race White | 57 Participants | 62 Participants | 13 Participants | 16 Participants | 148 Participants |
| Sex: Female, Male Female | 35 Participants | 44 Participants | 16 Participants | 17 Participants | 112 Participants |
| Sex: Female, Male Male | 38 Participants | 29 Participants | 3 Participants | 5 Participants | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 26 / 73 | 28 / 73 | 12 / 19 | 5 / 22 |
| serious Total, serious adverse events | 2 / 73 | 2 / 73 | 1 / 19 | 1 / 22 |
Outcome results
Primary
Change From Baseline to End of Treatment (EoT) in Mean Volume Voided (MVV) Per Micturition
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.
Time frame: Baseline and Week 12
Population: Full Analysis Set (FAS) consists of all randomized patients that took at least one dose of double-blind study medication after randomization and provided both valid baseline and post-baseline values for the primary efficacy endpoint. Missing values at EoT were imputed using the last observation carried forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Children | Change From Baseline to End of Treatment (EoT) in Mean Volume Voided (MVV) Per Micturition | 13.4 mL | Standard Error 4.8 |
| Solifenacin Succinate Suspension Children | Change From Baseline to End of Treatment (EoT) in Mean Volume Voided (MVV) Per Micturition | 25.5 mL | Standard Error 4.8 |
| Placebo Adolescents | Change From Baseline to End of Treatment (EoT) in Mean Volume Voided (MVV) Per Micturition | 6.9 mL | Standard Error 14.6 |
| Solifenacin Succinate Suspension Adolescents | Change From Baseline to End of Treatment (EoT) in Mean Volume Voided (MVV) Per Micturition | 2.3 mL | Standard Error 14 |
Comparison: The following hypotheses were tested at the 2-sided significance level 0.05:~* H0: Change from baseline to EoT in mean MVV per micturition is the same for placebo and solifenacin succinate oral suspension~* H1: Change from baseline to EoT in mean MVV per micturition is not the same for placebo and solifenacin succinate oral suspensionp-value: 0.04695% CI: [0.2, 24]ANCOVA
95% CI: [-36.7, 27.4]
Secondary
Apparent Terminal Elimination Half-Life (T1/2) of Solifenacin
Pharmacokinetic sampling was performed at steady state at the end of treatment.
Time frame: 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).
Population: The study analysis population for this endpoint consisted of the PKAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Children | Apparent Terminal Elimination Half-Life (T1/2) of Solifenacin | 27.3 hours | Standard Deviation 5.486 |
| Solifenacin Succinate Suspension Children | Apparent Terminal Elimination Half-Life (T1/2) of Solifenacin | 30.98 hours | Standard Deviation 7.147 |
| Placebo Adolescents | Apparent Terminal Elimination Half-Life (T1/2) of Solifenacin | 24.84 hours | — |
| Solifenacin Succinate Suspension Adolescents | Apparent Terminal Elimination Half-Life (T1/2) of Solifenacin | 26.85 hours | Standard Deviation 7.475 |
| Adolescents PED 10 | Apparent Terminal Elimination Half-Life (T1/2) of Solifenacin | 41.27 hours | Standard Deviation 17.44 |
Secondary
Apparent Total Body Clearance (CL/F) of Solifenacin
Pharmacokinetic sampling was performed at steady state at the end of treatment.
Time frame: 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).
Population: The study analysis population for this endpoint consisted of the PKAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Children | Apparent Total Body Clearance (CL/F) of Solifenacin | 6.968 L/h | Standard Deviation 2.129 |
| Solifenacin Succinate Suspension Children | Apparent Total Body Clearance (CL/F) of Solifenacin | 7.608 L/h | Standard Deviation 1.782 |
| Placebo Adolescents | Apparent Total Body Clearance (CL/F) of Solifenacin | 14.56 L/h | — |
| Solifenacin Succinate Suspension Adolescents | Apparent Total Body Clearance (CL/F) of Solifenacin | 8.773 L/h | Standard Deviation 3.763 |
| Adolescents PED 10 | Apparent Total Body Clearance (CL/F) of Solifenacin | 11.3 L/h | Standard Deviation 7.294 |
Secondary
Apparent Volume of Distribution (Vz/F) of Solifenacin
Pharmacokinetic sampling was performed at steady state at the end of treatment.
Time frame: 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).
Population: The study analysis population for this endpoint consisted of the PKAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Children | Apparent Volume of Distribution (Vz/F) of Solifenacin | 272.4 L | Standard Deviation 96.84 |
| Solifenacin Succinate Suspension Children | Apparent Volume of Distribution (Vz/F) of Solifenacin | 329.5 L | Standard Deviation 63.32 |
| Placebo Adolescents | Apparent Volume of Distribution (Vz/F) of Solifenacin | 521.9 L | — |
| Solifenacin Succinate Suspension Adolescents | Apparent Volume of Distribution (Vz/F) of Solifenacin | 315.7 L | Standard Deviation 96.23 |
| Adolescents PED 10 | Apparent Volume of Distribution (Vz/F) of Solifenacin | 561.7 L | Standard Deviation 181.7 |
Secondary
Area Under the Plasma Concentration - Time to Curve (AUC) for a Dose Interval (AUCtau) of Solifenacin
Pharmacokinetic sampling was performed at steady state at the end of treatment.
Time frame: 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).
Population: The study analysis population for this endpoint consisted of the PKAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Children | Area Under the Plasma Concentration - Time to Curve (AUC) for a Dose Interval (AUCtau) of Solifenacin | 298.7 ng*h/mL | Standard Deviation 80.35 |
| Solifenacin Succinate Suspension Children | Area Under the Plasma Concentration - Time to Curve (AUC) for a Dose Interval (AUCtau) of Solifenacin | 452.8 ng*h/mL | Standard Deviation 112.6 |
| Placebo Adolescents | Area Under the Plasma Concentration - Time to Curve (AUC) for a Dose Interval (AUCtau) of Solifenacin | 269.2 ng*h/mL | — |
| Solifenacin Succinate Suspension Adolescents | Area Under the Plasma Concentration - Time to Curve (AUC) for a Dose Interval (AUCtau) of Solifenacin | 560 ng*h/mL | Standard Deviation 216.8 |
| Adolescents PED 10 | Area Under the Plasma Concentration - Time to Curve (AUC) for a Dose Interval (AUCtau) of Solifenacin | 745.7 ng*h/mL | Standard Deviation 411 |
Secondary
Change From Baseline in Post Void Residual (PVR) Volume
Post Void Residual (PVR) Volume was assessed by ultrasonography or bladder scan.
Time frame: Baseline and Week 12
Population: The study analysis population for this endpoint consisted of the SAF.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Children | Change From Baseline in Post Void Residual (PVR) Volume | 0.07 mL | Standard Deviation 7.28 |
| Solifenacin Succinate Suspension Children | Change From Baseline in Post Void Residual (PVR) Volume | -0.99 mL | Standard Deviation 6.45 |
| Placebo Adolescents | Change From Baseline in Post Void Residual (PVR) Volume | -3.58 mL | Standard Deviation 4.72 |
| Solifenacin Succinate Suspension Adolescents | Change From Baseline in Post Void Residual (PVR) Volume | 0.95 mL | Standard Deviation 9.85 |
Secondary
Change From Baseline to End of Treatment in Daytime Maximum Volume Voided (DMaxVV) Per Micturition
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.
Time frame: Baseline and Week 12
Population: The study analysis population for this endpoint consisted of the FAS population. Missing values at EoT were imputed using the LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Children | Change From Baseline to End of Treatment in Daytime Maximum Volume Voided (DMaxVV) Per Micturition | 11.3 mL | Standard Error 11.2 |
| Solifenacin Succinate Suspension Children | Change From Baseline to End of Treatment in Daytime Maximum Volume Voided (DMaxVV) Per Micturition | 43.2 mL | Standard Error 11.1 |
| Placebo Adolescents | Change From Baseline to End of Treatment in Daytime Maximum Volume Voided (DMaxVV) Per Micturition | -8.4 mL | Standard Error 27 |
| Solifenacin Succinate Suspension Adolescents | Change From Baseline to End of Treatment in Daytime Maximum Volume Voided (DMaxVV) Per Micturition | -25.7 mL | Standard Error 26.3 |
p-value: 0.02495% CI: [4.3, 59.5]ANCOVA
95% CI: [-76.5, 41.9]
Secondary
Change From Baseline to End of Treatment in Mean Number of Daytime Incontinence Episodes Per 24 Hours
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.
Time frame: Baseline and Week 12
Population: Full analysis set including patients for whom data were available. Missing values at EoT were imputed using the last observation carried forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Children | Change From Baseline to End of Treatment in Mean Number of Daytime Incontinence Episodes Per 24 Hours | -1.1 daytime incontinence episodes | Standard Error 0.2 |
| Solifenacin Succinate Suspension Children | Change From Baseline to End of Treatment in Mean Number of Daytime Incontinence Episodes Per 24 Hours | -1.2 daytime incontinence episodes | Standard Error 0.2 |
| Placebo Adolescents | Change From Baseline to End of Treatment in Mean Number of Daytime Incontinence Episodes Per 24 Hours | -0.2 daytime incontinence episodes | Standard Error 0.4 |
| Solifenacin Succinate Suspension Adolescents | Change From Baseline to End of Treatment in Mean Number of Daytime Incontinence Episodes Per 24 Hours | -0.8 daytime incontinence episodes | Standard Error 0.4 |
p-value: 0.40295% CI: [-0.5, 0.3]ANCOVA
95% CI: [-1.5, 0.4]
Secondary
Change From Baseline to End of Treatment in Mean Number of Daytime Micturitions Per 24 Hours
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.
Time frame: Baseline and week 12
Population: The study analysis population for this endpoint consisted of the FAS population. Missing values at EoT were imputed using the LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Children | Change From Baseline to End of Treatment in Mean Number of Daytime Micturitions Per 24 Hours | -1.1 daytime micturitions | Standard Error 0.2 |
| Solifenacin Succinate Suspension Children | Change From Baseline to End of Treatment in Mean Number of Daytime Micturitions Per 24 Hours | -1.2 daytime micturitions | Standard Error 0.2 |
| Placebo Adolescents | Change From Baseline to End of Treatment in Mean Number of Daytime Micturitions Per 24 Hours | -0.5 daytime micturitions | Standard Error 0.5 |
| Solifenacin Succinate Suspension Adolescents | Change From Baseline to End of Treatment in Mean Number of Daytime Micturitions Per 24 Hours | -0.3 daytime micturitions | Standard Error 0.5 |
p-value: 0.6495% CI: [-0.8, 0.5]ANCOVA
95% CI: [-0.9, 1.4]
Secondary
Change From Baseline to End of Treatment in Mean Number of Dry (Incontinence-Free) Days Per 7 Days
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.
Time frame: Baseline and Week 12
Population: The study analysis population for this endpoint consisted of the FAS population. Missing values at EoT were imputed using the LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Children | Change From Baseline to End of Treatment in Mean Number of Dry (Incontinence-Free) Days Per 7 Days | 1.7 Dry Days | Standard Error 0.3 |
| Solifenacin Succinate Suspension Children | Change From Baseline to End of Treatment in Mean Number of Dry (Incontinence-Free) Days Per 7 Days | 1.3 Dry Days | Standard Error 0.3 |
| Placebo Adolescents | Change From Baseline to End of Treatment in Mean Number of Dry (Incontinence-Free) Days Per 7 Days | 1.5 Dry Days | Standard Error 0.8 |
| Solifenacin Succinate Suspension Adolescents | Change From Baseline to End of Treatment in Mean Number of Dry (Incontinence-Free) Days Per 7 Days | 1.6 Dry Days | Standard Error 0.7 |
p-value: 0.56395% CI: [-1, 0.3]ANCOVA
95% CI: [-1.6, 1.9]
Secondary
Change From Baseline to End of Treatment in Mean Number of Dry (Incontinence-Free) Nighttimes Per 7 Days
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.
Time frame: Baseline and Week 12
Population: The study analysis population for this endpoint consisted of the FAS population. Missing values at EoT were imputed using the LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Children | Change From Baseline to End of Treatment in Mean Number of Dry (Incontinence-Free) Nighttimes Per 7 Days | 0.7 Dry Nights | Standard Error 0.2 |
| Solifenacin Succinate Suspension Children | Change From Baseline to End of Treatment in Mean Number of Dry (Incontinence-Free) Nighttimes Per 7 Days | 0.4 Dry Nights | Standard Error 0.2 |
| Placebo Adolescents | Change From Baseline to End of Treatment in Mean Number of Dry (Incontinence-Free) Nighttimes Per 7 Days | -0.1 Dry Nights | Standard Error 0.4 |
| Solifenacin Succinate Suspension Adolescents | Change From Baseline to End of Treatment in Mean Number of Dry (Incontinence-Free) Nighttimes Per 7 Days | 0.4 Dry Nights | Standard Error 0.4 |
p-value: 0.7795% CI: [-0.9, 0.3]ANCOVA
95% CI: [-0.4, 1.3]
Secondary
Change From Baseline to End of Treatment in Mean Number of Grade 3 or 4 Urgency Episodes Per 24 Hours in Adolescents
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.
Time frame: Baseline and Week 12
Population: The study analysis population for this endpoint consisted of the FAS including participants for whom data were available (adolescents only). Missing values at EoT were imputed using the last observation carried forward (LOCF) method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Children | Change From Baseline to End of Treatment in Mean Number of Grade 3 or 4 Urgency Episodes Per 24 Hours in Adolescents | -0.7 urgency episodes | Standard Error 0.5 |
| Solifenacin Succinate Suspension Children | Change From Baseline to End of Treatment in Mean Number of Grade 3 or 4 Urgency Episodes Per 24 Hours in Adolescents | -1.0 urgency episodes | Standard Error 0.5 |
95% CI: [-1.4, 0.8]
Secondary
Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours
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.
Time frame: Baseline and Week 12
Population: The study analysis population for this endpoint consisted of the FAS population. Missing values at EoT were imputed using the LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Children | Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | -1.2 incontinence episodes | Standard Error 0.2 |
| Solifenacin Succinate Suspension Children | Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | -1.1 incontinence episodes | Standard Error 0.2 |
| Placebo Adolescents | Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | -0.7 incontinence episodes | Standard Error 0.4 |
| Solifenacin Succinate Suspension Adolescents | Change From Baseline to End of Treatment in Mean Number of Incontinence Episodes Per 24 Hours | -0.6 incontinence episodes | Standard Error 0.4 |
p-value: 0.76395% CI: [-0.3, 0.4]ANCOVA
95% CI: [-0.8, 1]
Secondary
Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours
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.
Time frame: Baseline and Week 12
Population: The study analysis population for this endpoint consisted of the FAS population. Missing values at EoT were imputed using the LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Children | Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours | -0.8 micturitions | Standard Error 0.2 |
| Solifenacin Succinate Suspension Children | Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours | -1.1 micturitions | Standard Error 0.2 |
| Placebo Adolescents | Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours | -0.6 micturitions | Standard Error 0.5 |
| Solifenacin Succinate Suspension Adolescents | Change From Baseline to End of Treatment in Mean Number of Micturitions Per 24 Hours | -0.4 micturitions | Standard Error 0.4 |
p-value: 0.30395% CI: [-0.8, 0.2]ANCOVA
95% CI: [-0.9, 1.1]
Secondary
Change From Baseline to End of Treatment in Mean Number of Nighttime Incontinence Episodes Per 24 Hours
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.
Time frame: Baseline and Week 12
Population: The study analysis population for this endpoint consisted of the FAS population. Missing values at EoT were imputed using the LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Children | Change From Baseline to End of Treatment in Mean Number of Nighttime Incontinence Episodes Per 24 Hours | -0.2 nighttime incontinence episodes | Standard Error 0 |
| Solifenacin Succinate Suspension Children | Change From Baseline to End of Treatment in Mean Number of Nighttime Incontinence Episodes Per 24 Hours | -0.1 nighttime incontinence episodes | Standard Error 0 |
| Placebo Adolescents | Change From Baseline to End of Treatment in Mean Number of Nighttime Incontinence Episodes Per 24 Hours | -0.2 nighttime incontinence episodes | Standard Error 0.1 |
| Solifenacin Succinate Suspension Adolescents | Change From Baseline to End of Treatment in Mean Number of Nighttime Incontinence Episodes Per 24 Hours | -0.2 nighttime incontinence episodes | Standard Error 0.1 |
p-value: 0.6395% CI: [0, 0.2]ANCOVA
95% CI: [-0.2, 0.2]
Secondary
Change From Baseline to End of Treatment in Mean Number of Nighttime Micturitions Per 24 Hours
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 frame: Baseline and Week 12
Population: The study analysis population for this endpoint consisted of the FAS population. Missing values at EoT were imputed using the LOCF method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo Children | Change From Baseline to End of Treatment in Mean Number of Nighttime Micturitions Per 24 Hours | 0.0 nighttime micturitions | Standard Error 0.1 |
| Solifenacin Succinate Suspension Children | Change From Baseline to End of Treatment in Mean Number of Nighttime Micturitions Per 24 Hours | -0.1 nighttime micturitions | Standard Error 0.1 |
| Placebo Adolescents | Change From Baseline to End of Treatment in Mean Number of Nighttime Micturitions Per 24 Hours | 0.4 nighttime micturitions | Standard Error 0.3 |
| Solifenacin Succinate Suspension Adolescents | Change From Baseline to End of Treatment in Mean Number of Nighttime Micturitions Per 24 Hours | 0.1 nighttime micturitions | Standard Error 0.3 |
p-value: 0.84695% CI: [-0.3, 0.1]ANCOVA
95% CI: [-1, 0.5]
Secondary
Maximum Concentration (Cmax) of Solifenacin
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).
Time frame: 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).
Population: The study analysis population for this endpoint consisted of the PKAS. The PKAS consisted of the subset of the Safety Analysis Set (SAF) for which plasma concentration data were available to facilitate derivation of at least 1 pharmacokinetic parameter and for whom the time of last dose prior to sampling was known.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Children | Maximum Concentration (Cmax) of Solifenacin | 16.67 ng/mL | Standard Deviation 4.593 |
| Solifenacin Succinate Suspension Children | Maximum Concentration (Cmax) of Solifenacin | 26.24 ng/mL | Standard Deviation 6.617 |
| Placebo Adolescents | Maximum Concentration (Cmax) of Solifenacin | 17.08 ng/mL | — |
| Solifenacin Succinate Suspension Adolescents | Maximum Concentration (Cmax) of Solifenacin | 33.48 ng/mL | Standard Deviation 11.93 |
| Adolescents PED 10 | Maximum Concentration (Cmax) of Solifenacin | 42.85 ng/mL | Standard Deviation 21.44 |
Secondary
Number of Participants With Adverse Events (AEs)
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.
Time frame: From the first dose of study drug until 7 days after last dose of study medication (13 weeks).
Population: The study analysis for this endpoint consisted of the Safety Analysis Set (SAF), the SAF consisted of all patients who received at least 1 dose of double-blind study medication and for whom any safety data were reported after first dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo Children | Number of Participants With Adverse Events (AEs) | Any TEAE | 45 participants |
| Placebo Children | Number of Participants With Adverse Events (AEs) | TEAEs Leading to Discontinuation | 1 participants |
| Placebo Children | Number of Participants With Adverse Events (AEs) | Drug-related Serious TEAEs | 1 participants |
| Placebo Children | Number of Participants With Adverse Events (AEs) | Drug Related TEAEs | 9 participants |
| Placebo Children | Number of Participants With Adverse Events (AEs) | Drug-related TEAEs Leading to Permanent Discont. | 1 participants |
| Placebo Children | Number of Participants With Adverse Events (AEs) | Deaths | 0 participants |
| Placebo Children | Number of Participants With Adverse Events (AEs) | Serious TEAEs | 2 participants |
| Solifenacin Succinate Suspension Children | Number of Participants With Adverse Events (AEs) | TEAEs Leading to Discontinuation | 6 participants |
| Solifenacin Succinate Suspension Children | Number of Participants With Adverse Events (AEs) | Serious TEAEs | 2 participants |
| Solifenacin Succinate Suspension Children | Number of Participants With Adverse Events (AEs) | Deaths | 0 participants |
| Solifenacin Succinate Suspension Children | Number of Participants With Adverse Events (AEs) | Drug-related Serious TEAEs | 0 participants |
| Solifenacin Succinate Suspension Children | Number of Participants With Adverse Events (AEs) | Drug-related TEAEs Leading to Permanent Discont. | 3 participants |
| Solifenacin Succinate Suspension Children | Number of Participants With Adverse Events (AEs) | Drug Related TEAEs | 14 participants |
| Solifenacin Succinate Suspension Children | Number of Participants With Adverse Events (AEs) | Any TEAE | 44 participants |
| Placebo Adolescents | Number of Participants With Adverse Events (AEs) | Serious TEAEs | 1 participants |
| Placebo Adolescents | Number of Participants With Adverse Events (AEs) | Any TEAE | 12 participants |
| Placebo Adolescents | Number of Participants With Adverse Events (AEs) | Drug Related TEAEs | 2 participants |
| Placebo Adolescents | Number of Participants With Adverse Events (AEs) | Deaths | 0 participants |
| Placebo Adolescents | Number of Participants With Adverse Events (AEs) | Drug-related Serious TEAEs | 0 participants |
| Placebo Adolescents | Number of Participants With Adverse Events (AEs) | TEAEs Leading to Discontinuation | 2 participants |
| Placebo Adolescents | Number of Participants With Adverse Events (AEs) | Drug-related TEAEs Leading to Permanent Discont. | 1 participants |
| Solifenacin Succinate Suspension Adolescents | Number of Participants With Adverse Events (AEs) | Deaths | 0 participants |
| Solifenacin Succinate Suspension Adolescents | Number of Participants With Adverse Events (AEs) | Drug-related TEAEs Leading to Permanent Discont. | 1 participants |
| Solifenacin Succinate Suspension Adolescents | Number of Participants With Adverse Events (AEs) | TEAEs Leading to Discontinuation | 2 participants |
| Solifenacin Succinate Suspension Adolescents | Number of Participants With Adverse Events (AEs) | Drug Related TEAEs | 3 participants |
| Solifenacin Succinate Suspension Adolescents | Number of Participants With Adverse Events (AEs) | Any TEAE | 9 participants |
| Solifenacin Succinate Suspension Adolescents | Number of Participants With Adverse Events (AEs) | Drug-related Serious TEAEs | 0 participants |
| Solifenacin Succinate Suspension Adolescents | Number of Participants With Adverse Events (AEs) | Serious TEAEs | 1 participants |
Secondary
Plasma Concentration Before Drug Administration (Ctrough) of Solifenacin
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.
Time frame: 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).
Population: The study analysis population for this endpoint consisted of the PKAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Children | Plasma Concentration Before Drug Administration (Ctrough) of Solifenacin | 9.534 ng/mL | Standard Deviation 3.083 |
| Solifenacin Succinate Suspension Children | Plasma Concentration Before Drug Administration (Ctrough) of Solifenacin | 16.1 ng/mL | Standard Deviation 4.951 |
| Placebo Adolescents | Plasma Concentration Before Drug Administration (Ctrough) of Solifenacin | 8.828 ng/mL | — |
| Solifenacin Succinate Suspension Adolescents | Plasma Concentration Before Drug Administration (Ctrough) of Solifenacin | 19.05 ng/mL | Standard Deviation 8.7 |
| Adolescents PED 10 | Plasma Concentration Before Drug Administration (Ctrough) of Solifenacin | 27.94 ng/mL | Standard Deviation 16.76 |
Secondary
Time to Attain Maximum Concentration (Tmax) of Solifenacin
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.
Time frame: 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).
Population: The study analysis population for this endpoint consisted of the PKAS.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Children | Time to Attain Maximum Concentration (Tmax) of Solifenacin | 2.933 hours | Standard Deviation 0.5354 |
| Solifenacin Succinate Suspension Children | Time to Attain Maximum Concentration (Tmax) of Solifenacin | 3.175 hours | Standard Deviation 0.561 |
| Placebo Adolescents | Time to Attain Maximum Concentration (Tmax) of Solifenacin | 2.8 hours | — |
| Solifenacin Succinate Suspension Adolescents | Time to Attain Maximum Concentration (Tmax) of Solifenacin | 2.874 hours | Standard Deviation 0.5268 |
| Adolescents PED 10 | Time to Attain Maximum Concentration (Tmax) of Solifenacin | 2.85 hours | Standard Deviation 0.4733 |