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

Neurogenic Detrusor Overactivity Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00712322
• Other study ID #: CDAR328B2201
• Status: Terminated
• Phase: Phase 2
• Start date: October 7, 2008
• Est. completion date: May 23, 2013

Study information

• Verified date: September 2021
• Source: Warner Chilcott
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 35
• Est. completion date: May 23, 2013
• Est. primary completion date: May 23, 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 15 Years

Eligibility

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.

Related Conditions & MeSH terms

• Neurogenic Detrusor Overactivity
• Urinary Bladder, Overactive

Intervention

Drug:
• Darifenacin
Following a 7-day washout period, participants received darifenacin liquid oral suspension up to 14 days.

Locations

Country	Name	City	State
Colombia	Fundacion Hospital Infantil, Universitario De San Jose	Bogota
Colombia	Fundación Valle de Lili	Cali
Colombia	Hospital Pablo Tobon Uribe	Medellín
United States	Pediatric & Adolescent Urology, Inc Akron Children's Hospital	Akron	Ohio
United States	Children's Hospital, Karp 8210	Boston	Massachusetts
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Children's Hospital of Michigan	Detroit	Michigan
United States	Pediatric Urology Associates, PC	Lake Success	New York
United States	Oregon Health & Science University	Portland	Oregon
United States	Washington University Pediatric Urology	Saint Louis	Missouri
United States	University of California at San Diego	San Diego	California
United States	Pediatric Urology Associates PC	Tarrytown	New York

Sponsors (1)

Lead Sponsor	Collaborator
Warner Chilcott

Countries where clinical trial is conducted

United States,  Colombia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Mean Maximum Bladder Capacity (MBC)	MBC was defined as the volume of urine at which significant urinary leakage (i.e. leakage that prevents further volume increase) or significant discomfort/pain occurs, or a detrusor pressure at 40 centimeter (cm) H2O was reached.	Baseline (Day 0) to Day 14
Secondary	Change From Baseline in Mean Volume at First Contraction	Average volume of urine collected by catheterization at first contraction.	Baseline (Day 0) to Day 14
Secondary	Change From Baseline in Detrusor Pressure at First Contraction		Baseline (Day 0) to Day 14
Secondary	Change From Baseline in Mean Volume at First Detectable Leakage	Average volume of urine collected by catheterization at first detectable leakage.	Baseline (Day 0) to Day 14
Secondary	Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure		Baseline (Day 0) to Day 14
Secondary	Change From Baseline in Mean Catheterization Volume	Average volume of urine was collected by catheterization and was recorded in a bladder diary. Bladder volume was assessed by urodynamics. The bladder diary entries completed on any 2 consecutive days after completing wash-out and prior to the baseline urodynamic examination on Visit 2 was used to calculate the baseline (Day-1) i.e. Visit 2 values. Similarly, the bladder diary entries completed on any 2 consecutive days during the week prior to the final study visit on Day 14 i.e. Visit 4 was used to calculate the Visit 4 values. The positive change from baseline indicates improvement.	Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14
Secondary	Change From Baseline in Total Pad Weight In-between Catheterizations	Urodynamic test was used to assess the total pad weight in-between catheterizations. The change in total pad weight in-between catheterizations was recorded in the bladder diary. The bladder diary entries completed on any 2 consecutive days after completing wash-out and prior to the baseline urodynamic examination on Visit 2 was used to calculate the baseline (Day-1) i.e. Visit 2 values. Similarly, the bladder diary entries completed on any 2 consecutive days during the week prior to the final study visit on Day 14 i.e. Visit 4 was used to calculate the Visit 4 values. The positive change from baseline indicates improvement.	Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14
Secondary	Change From Baseline in Mean Catheterization Volume at First Awakening	The change in urine volume at first awakening catherization was recorded by the participant in a bladder diary. Bladder volume was assessed by urodynamics. The bladder diary entries completed on any 2 consecutive days after completing wash-out and prior to the baseline urodynamic examination on Visit 2 was used to calculate the baseline (Day-1) i.e. Visit 2 values. Similarly, the bladder diary entries completed on any 2 consecutive days during the week prior to the final study visit on Day 14 i.e. Visit 4 was used to calculate the Visit 4 values. The positive change from baseline indicates improvement.	Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14