Clinical trial NCT00712322: A Two-week Open-label Pharmacodynamic and Pharmacokinetic Study of Multiple Doses of a Darifenacin Liquid Oral Suspension in Children (2 - 15 Years) With Neurogenic Detrusor Overactivity
Official title: A 14-day, Open-label, Multicenter, Dose-escalating, Sequential Cohort Study to Evaluate Pharmacodynamics (Urodynamics) and Pharmacokinetics, Clinical Efficacy, Tolerability and Safety Following Multiple Doses (mg/kg/Day) of a Darifenacin Liquid Oral Suspension Given BID in Children, Ages 2 - 15 Years, With Neurogenic Detrusor Overactivity
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Neurogenic Detrusor Overactivity
Keywords: Pediatric, Children, Urodynamics, Oral Suspension, Overactive bladder, Dose-finding, Neurogenic Detrusor Overactivity, Meningomyelocele, Spinal cord injury
Lead sponsor: Warner Chilcott
Sponsor class: INDUSTRY
First posted: 2008-07-09
Enrollment: 35
Sex: ALL
Minimum age (years): 2
Maximum age (years): 15
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This study will evaluate the pharmacodynamics and pharmacokinetics of darifenacin liquid oral suspension in children, ages 2-15 years, with neurogenic detrusor overactivity. The results will support a benefit-risk based dosage recommendation for phase IIIa clinical trials.


Eligibility criteria: Inclusion Criteria:

* Male and female participants ages 2-15 years
* Documented detrusor overactivity associated with a known neurological condition such as meningomyelocele or spinal cord injury, and confirmed by urodynamics at baseline
* Using clean intermittent catheterization (CIC) on a regular basis
* Participating in a bowel program on a regular basis
* Able to swallow the study medication in accordance to the protocol
* Participants and/or parent/guardian able to complete the bladder diary and follow the study procedures

Exclusion Criteria:

* Treatment with drugs known to significantly affect the urinary bladder and urinary bladder outlet function
* Fecal impaction. Participants may be included, once this condition has resolved
* Clinically significant anatomical abnormalities or acquired disorders of the urinary tract
* Previous reconstructive surgery (augmentation etc.) of the bladder or bladder outlet
* Symptomatic urinary tract infection unresolved at time of urodynamic study and/or completion of bladder diary.
* Diabetes insipidus
* Electro stimulation therapy or bladder training within 2 weeks prior to Visit 1 and at any time during the study
* Concomitant diseases, in which the use of darifenacin is contraindicated
* History of hypersensitivity to darifenacin or to drugs with similar chemical structures
* Participants with any physical and cognitive impairment or any other condition which in the opinion of the investigator makes the participants unsuitable for inclusion
* Female adolescent of child-bearing potential, unless using an acceptable method of contraception
* Pregnant or nursing (lactating) female adolescents Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Change From Baseline in Mean Maximum Bladder Capacity (MBC)
timeFrame: Baseline (Day 0) to Day 14
Secondary outcomes:
measure: Change From Baseline in Mean Volume at First Contraction
timeFrame: Baseline (Day 0) to Day 14
measure: Change From Baseline in Detrusor Pressure at First Contraction
timeFrame: Baseline (Day 0) to Day 14
measure: Change From Baseline in Mean Volume at First Detectable Leakage
timeFrame: Baseline (Day 0) to Day 14
measure: Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure
timeFrame: Baseline (Day 0) to Day 14
measure: Change From Baseline in Mean Catheterization Volume
timeFrame: Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14
measure: Change From Baseline in Total Pad Weight In-between Catheterizations
timeFrame: Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14
measure: Change From Baseline in Mean Catheterization Volume at First Awakening
timeFrame: Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California at San Diego
state: California
city: Boston
country: United States
facility: Children's Hospital, Karp 8210
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hospital of Michigan
state: Michigan
city: Saint Louis
country: United States
facility: Washington University Pediatric Urology
state: Missouri
city: Lake Success
country: United States
facility: Pediatric Urology Associates, PC
state: New York
city: Tarrytown
country: United States
facility: Pediatric Urology Associates PC
state: New York
city: Akron
country: United States
facility: Pediatric & Adolescent Urology, Inc Akron Children's Hospital
state: Ohio
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Bogota
country: Colombia
facility: Fundacion Hospital Infantil, Universitario De San Jose
city: Cali
country: Colombia
facility: Fundación Valle de Lili
city: Medellín
country: Colombia
facility: Hospital Pablo Tobon Uribe
Study officials:
affiliation: Warner Chilcott (US) LLC
name: Herman Ellman, MD
role: STUDY_DIRECTOR
References: