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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 (LION)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Europe B.V. )
ClinicalTrials.gov Identifier:
NCT01565707
First received: March 27, 2012
Last updated: February 27, 2017
Last verified: February 2017
  Purpose

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.


Condition Intervention Phase
Urinary Bladder, Overactive Drug: Solifenacin Succinate Suspension Drug: Placebo Behavioral: Urotherapy Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Astellas Pharma Inc ( Astellas Pharma Europe B.V. ):

Primary Outcome Measures:
  • Change From Baseline to End of Treatment (EoT) in Mean Volume Voided (MVV) Per Micturition [ Time Frame: 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:
  • Change From Baseline to End of Treatment in Daytime Maximum Volume Voided (DMaxVV) Per Micturition [ Time Frame: 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 Incontinence Episodes Per 24 Hours [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ 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). ]
    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 to Attain Maximum Concentration (Tmax) of Solifenacin [ 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). ]
    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 [ 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). ]
    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 [ 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). ]
    Pharmacokinetic sampling was performed at steady state at the end of treatment.

  • Apparent Terminal Elimination Half-Life (T1/2) of Solifenacin [ 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). ]
    Pharmacokinetic sampling was performed at steady state at the end of treatment.

  • Apparent Total Body Clearance (CL/F) of Solifenacin [ 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). ]
    Pharmacokinetic sampling was performed at steady state at the end of treatment.

  • Apparent Volume of Distribution (Vz/F) of Solifenacin [ 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). ]
    Pharmacokinetic sampling was performed at steady state at the end of treatment.

  • Number of Participants With Adverse Events (AEs) [ Time Frame: 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 [ Time Frame: Baseline and Week 12 ]
    Post Void Residual (PVR) Volume was assessed by ultrasonography or bladder scan.


Enrollment: 189
Study Start Date: June 2012
Study Completion Date: January 2014
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Children
Children aged 5 to 11 years received matching placebo suspension once a day for 12 weeks.
Drug: 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.
Other Name: Bladder training
Experimental: 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.
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.
Other Name: YM905
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.
Other Name: Bladder training
Placebo Comparator: Placebo Adolescents
Adolescents aged 12 to 17 years received matching placebo suspension once a day for 12 weeks.
Drug: 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.
Other Name: Bladder training
Placebo Comparator: 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.
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.
Other Name: YM905
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.
Other Name: Bladder training

  Eligibility

Ages Eligible for Study:   5 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01565707

  Show 46 Study Locations
Sponsors and Collaborators
Astellas Pharma Europe B.V.
Investigators
Study Chair: Clinical Study Manager Astellas Pharma Europe B.V.
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Astellas Pharma Europe B.V.
ClinicalTrials.gov Identifier: NCT01565707     History of Changes
Other Study ID Numbers: 905-CL-076
2011-002066-20 ( EudraCT Number )
Study First Received: March 27, 2012
Results First Received: December 5, 2016
Last Updated: February 27, 2017

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Europe B.V. ):
Pediatric
Solifenacin succinate suspension
Phase 3
Pharmacokinetics
Overactive bladder (OAB)

Additional relevant MeSH terms:
Urinary Bladder, Overactive
Urinary Bladder Diseases
Urologic Diseases
Lower Urinary Tract Symptoms
Urological Manifestations
Signs and Symptoms
Solifenacin Succinate
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Urological Agents

ClinicalTrials.gov processed this record on June 28, 2017