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

Urinary Bladder, Overactive Clinical Trial

— LION  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01565707
• Other study ID #: 905-CL-076
• Secondary ID: 2011-002066-20
• Status: Completed
• Phase: Phase 3
• Start date: June 7, 2012
• Est. completion date: January 2, 2014

Study information

• Verified date: October 2018
• Source: Astellas Pharma Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 189
• Est. completion date: January 2, 2014
• Est. primary completion date: December 31, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Urinary Bladder, Overactive

Intervention

Drug:
• Solifenacin Succinate Suspension
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.
• Placebo
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.

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.

Locations

Country	Name	City	State
Belgium	Site: 3202	Antwerp
Belgium	Site: 3209	Antwerp
Belgium	Site: 3208	Charleroi
Belgium	Site: 3201	Gent
Belgium	Site: 3203	Gent
Belgium	Site: 3204	Kortrijk
Belgium	Site: 3205	Leuven
Brazil	Site: 5507	Campinas
Brazil	Site: 5506	Curitiba
Canada	Site: 1005	Hamilton
Canada	Site: 1001	Quebec
Denmark	Site: 4503	Aalborg
Denmark	Site: 4501	Aarhus N
Denmark	Site: 4504	Koge
Denmark	Site: 4502	Kolding
Former Serbia and Montenegro	Site: 3810	Belgrade
Former Serbia and Montenegro	Site: 3812	Novi Sad
Korea, Republic of	Site:8203	Daegu
Korea, Republic of	Site: 8206	Incheon
Korea, Republic of	Site: 8201	Seoul
Korea, Republic of	Site: 8207	Seoul
Korea, Republic of	Site:8202	Seoul
Mexico	Site: 5202	Mexico City
Mexico	Site: 5205	Mexico City
Norway	Site: 4701	Bergen
Norway	Site: 4702	Trondheim
Philippines	Site: 6301	Quezon City
Poland	Site: 4803	Gdansk
Poland	Site: 4805	Gdansk
Poland	Site: 4804	Lubin
Poland	Site: 4801	Warsaw
South Africa	Site: 2703	Cape Town
Sweden	Site: 4606	Gothenburg
Sweden	Site: 4601	Jonkoping
Sweden	Site: 4603	Skovde
Sweden	Site: 4602	Stockholm
Sweden	Site: 4605	Umea
Turkey	Site: 9001	Ankara
Turkey	Site: 9002	Izmir
Ukraine	Site: 3853	Dnipropetrovsk
Ukraine	Site: 3854	Kharkiv
Ukraine	Site: 3850	Kiev
United Kingdom	Site: 4403	Leeds
United Kingdom	Site: 4401	Sheffield
United States	Site: 1015	Albany	New York
United States	Site: 1006	Shreveport	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Astellas Pharma Europe B.V.

Countries where clinical trial is conducted

United States,  Belgium,  Brazil,  Canada,  Denmark,  Former Serbia and Montenegro,  Korea, Republic of,  Mexico,  Norway,  Philippines,  Poland,  South Africa,  Sweden,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Baseline and Week 12
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.	Baseline and Week 12
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.	Baseline and Week 12
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.	Baseline and Week 12
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.	Baseline and Week 12
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.	Baseline and Week 12
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.	Baseline and Week 12
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.	Baseline and Week 12
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.	Baseline and week 12
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.	Baseline and Week 12
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.	Baseline and Week 12
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).	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).
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.	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).
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.	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).
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.	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).
Secondary	Apparent Terminal Elimination Half-Life (T1/2) of Solifenacin	Pharmacokinetic sampling was performed at steady state at the end of treatment.	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).
Secondary	Apparent Total Body Clearance (CL/F) of Solifenacin	Pharmacokinetic sampling was performed at steady state at the end of treatment.	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).
Secondary	Apparent Volume of Distribution (Vz/F) of Solifenacin	Pharmacokinetic sampling was performed at steady state at the end of treatment.	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).
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.	From the first dose of study drug until 7 days after last dose of study medication (13 weeks).
Secondary	Change From Baseline in Post Void Residual (PVR) Volume	Post Void Residual (PVR) Volume was assessed by ultrasonography or bladder scan.	Baseline and Week 12

External Links

•   Link to results on the Astellas Clinical Study Results website