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

Phase 2

Terminated

• Conditions: Neurogenic Detrusor Overactivity
• Interventions: Drug: Darifenacin

• Registration Number: NCT00712322
• Lead Sponsor: Warner Chilcott

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2008-07-03
• Study First Submitted QC: 2008-07-03
• Study First Posted: 2008-07-09
• Study Start: 2008-10-07
• Primary Completion: 2013-05-23
• Study Completion: 2013-05-23
• Status Verified: 2021-09
• Results First Submitted: 2022-05-13
• Results First Submitted QC: 2022-05-13
• Last Update Submitted: 2022-05-13
• Results First Posted: 2022-06-09
• Last Update Posted: 2022-06-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 35

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Cohort 2 (Darifenacin 0.0625 mg/kg/day)	Darifenacin	Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.0625 mg/kg/day dispensed per BID dosing, for 14 days.
Cohort 1 (Darifenacin 0.030 mg/kg/day)	Darifenacin	Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.030 milligrams/kilogram/day (mg/kg/day) dispensed per twice a day (BID) dosing, for 14 days.
Cohort 3 (Darifenacin 0.125 mg/kg/day)	Darifenacin	Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.125 mg/kg/day dispensed per BID dosing, for 14 days.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Maximum Bladder Capacity (MBC)	Baseline (Day 0) to Day 14	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Mean Catheterization Volume at First Awakening	Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14	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.
Change From Baseline in Mean Volume at First Contraction	Baseline (Day 0) to Day 14	Average volume of urine collected by catheterization at first contraction.
Change From Baseline in Mean Volume at First Detectable Leakage	Baseline (Day 0) to Day 14	Average volume of urine collected by catheterization at first detectable leakage.
Change From Baseline in Detrusor Pressure at First Contraction	Baseline (Day 0) to Day 14
Change From Baseline in Mean Catheterization Volume	Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14	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.
Change From Baseline in Total Pad Weight In-between Catheterizations	Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14	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.
Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure	Baseline (Day 0) to Day 14

Trial Locations

Locations (12)

Children's Hospital of Michigan; 🇺🇸 Detroit, Michigan, United States

Pediatric Urology Associates, PC; 🇺🇸 Lake Success, New York, United States

Washington University Pediatric Urology; 🇺🇸 Saint Louis, Missouri, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

Pediatric Urology Associates PC; 🇺🇸 Tarrytown, New York, United States

Fundacion Hospital Infantil, Universitario De San Jose; 🇨🇴 Bogota, Colombia

Hospital Pablo Tobon Uribe; 🇨🇴 Medellín, Colombia

University of California at San Diego; 🇺🇸 San Diego, California, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

Children's Hospital, Karp 8210; 🇺🇸 Boston, Massachusetts, United States

Pediatric & Adolescent Urology, Inc Akron Children's Hospital; 🇺🇸 Akron, Ohio, United States

Fundación Valle de Lili; 🇨🇴 Cali, Colombia