Single-dose Study to Assess Pharmacokinetics of Solifenacin Succinate Suspension in Children and Adolescents

A Multicenter, Open-label, Single Ascending Dose Study to Evaluate Pharmacokinetics, Safety and Tolerability of Solifenacin Succinate Suspension in Pediatric Patients Aged 5 to 17 Years (Inclusive) With Overactive Bladder (OAB)

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.

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.

Inclusion Criteria:

• Symptoms of urgency, diagnosed as OAB according to International Children's Continence Society (ICCS) criteria
• Daytime urgency incontinence at least once/day

Exclusion Criteria:

• 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