Single-dose Study to Assess Pharmacokinetics of Solifenacin Succinate Suspension in Children and Adolescents
- Conditions
- Urinary Bladder, Overactive
- Interventions
- Registration Number
- NCT01262391
- Lead Sponsor
- Astellas Pharma Inc
- Brief Summary
This single-dose study will investigate how well solifenacin suspension is taken up, how long it stays in the body and how well it will be tolerated in children and adolescents aged 5-17 years with symptoms of overactive bladder.
- Detailed Description
This is a multicenter, open-label, sequential, single ascending dose study. The study will consist of three treatment groups in children and three treatment groups in adolescents, targeting equivalent exposure to the 2.5, 5 and 10 mg doses o.d. in adults at steady state. The study will be conducted in pediatric OAB patients to establish the single-dose PK and the acute safety profile of solifenacin aqueous suspension. Each of the six groups will consist of at least six patients.
The study will start with the lowest dose group in adolescent patients (12 to 17 years). When this group has completed the study, their safety and concentration data will be reviewed by a Safety Review Committee. If no safety concerns are evident according to pre-specified criteria, enrollment of children (5 to 11 years) in the lowest dose group and adolescents in the intermediate dose group will be started simultaneously. When these groups have completed the study, their safety data and drug concentration data will also be reviewed. If no safety concerns occurred, enrollment of children in the intermediate dose group and of adolescents in the highest dose group will be started simultaneously. Finally, after these groups completed the study and no safety concerns occurred during associated data review, enrollment of children in the highest dose group will start. Interim review of plasma exposure at lower doses will be used to adjust the next higher doses administered, if necessary.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 42
- Symptoms of urgency, diagnosed as OAB according to International Children's Continence Society (ICCS) criteria
- Daytime urgency incontinence at least once/day
- Daytime voiding frequency less than 5
- Uroflow indicative of pathology other than OAB
- Maximum voided volume > age expected capacity ([age +1] x 30) in ml
- Post voiding residual (PVR) > 10% of the functional bladder capacity
- Monosymptomatic enuresis
- Congenital anomalies of the genito-urinary tract or nervous system
- Current constipation (when treated the patient can enter the study)
- Current urinary tract infection (patient will be eligible for enrolment 14 days after a negative dipstick test, provided a second dipstick test, performed after these 14 days, is also negative)
- Serum creatinine more than or equal to 2 times the upper limit of normal (ULN)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than or equal to 2 times ULN, or bilirubin more than or equal to 1.5 times ULN
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description AD-PED 10 mg Solifenacin succinate suspension 10 mg Male and female adolescents aged 12 to less than 18 years old who receive PED of 10 mg of solifenacin succinate. CH-PED 5 mg Solifenacin succinate suspension 5 mg Male and female children aged 5 to less than 12 years old who receive PED of 5 mg of solifenacin succinate. CH-PED 10 mg Solifenacin succinate suspension 10 mg Male and female children aged 5 to less than 12 years old who receive PED of 10 mg of solifenacin succinate. AD-PED 2.5 mg Solifenacin succinate suspension 2.5 mg Male and female adolescents aged 12 to less than 18 years old who receive pediatric equivalent dose (PED) of 2.5 mg of solifenacin succinate. CH-PED 2.5 mg Solifenacin succinate suspension 2.5 mg Male and female children aged 5 to less than 12 years old who receive PED of 2.5 mg of solifenacin succinate. AD-PED 5 mg Solifenacin succinate suspension 5 mg Male and female adolescents aged 12 to less than 18 years old who receive PED of 5 mg of solifenacin succinate.
- Primary Outcome Measures
Name Time Method Maximum Concentration (Cmax) Day 1 predose up to Day 7 postdose Area Under the Concentration-time Curve Extrapolated to Infinity (AUCinf) Day 1 predose up to Day 7 postdose Time to Attain Cmax (tmax) Day 1 predose up to Day 7 postdose Apparent Total Body Clearance (CL/F) Day 1 predose up to Day 7 postdose Apparent Terminal Elimination Half-life (t1/2) Day 1 predose up to Day 7 postdose Area Under the Concentration-time Curve from the Time of Dosing Until the Last Measurable Concentration (AUClast) Day 1 predose up to Day 7 postdose Apparent Volume of Distribution During the Terminal Phase (Vz/F) Day 1 predose up to Day 7 postdose
- Secondary Outcome Measures
Name Time Method Number of Participants with Adverse Events (AEs) From the first dose of study drug up to 7 days postdose Safety is monitored by collecting AEs, which includes abnormal laboratory tests, vital signs or ECG data that are defined as an AE if the abnormality induces clinical signs or symptoms, requires active intervention, interruption or discontinuation of study medication or is clinically significant in the investigator's opinion. A treatment-emergent adverse event (TEAE) is defined as an AE that occurs or worsens after study drug administration. A serious AE (SAE) is any untoward medical occurrence that, at any dose: Results in death, is life-threatening, results in persistent or significant disability/incapacity, results in congenital anomaly, or birth defect, requires inpatient hospitalization or leads to prolongation of hospitalization or other medically important events.
Change from baseline in postvoid residual (PVR) volume Baseline (screening) and 4 hours postdose PVR volume is assessed by ultrasonography or bladder scan.