Back to resultsA 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
Primary Purpose
Neurogenic Detrusor Overactivity
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Darifenacin
Sponsored by
About this trial
This is an interventional treatment trial for Neurogenic Detrusor Overactivity focused on measuring Pediatric, Children, Urodynamics, Oral Suspension, Overactive bladder, Dose-finding, Neurogenic Detrusor Overactivity, Meningomyelocele, Spinal cord injury
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.
Sites / Locations
- University of California at San Diego
- Children's Hospital, Karp 8210
- Children's Hospital of Michigan
- Washington University Pediatric Urology
- Pediatric Urology Associates, PC
- Pediatric Urology Associates PC
- Pediatric & Adolescent Urology, Inc Akron Children's Hospital
- Cincinnati Children's Hospital Medical Center
- Oregon Health & Science University
- Fundacion Hospital Infantil, Universitario De San Jose
- Fundación Valle de Lili
- Hospital Pablo Tobon Uribe
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Cohort 1 (Darifenacin 0.030 mg/kg/day)
Cohort 2 (Darifenacin 0.0625 mg/kg/day)
Cohort 3 (Darifenacin 0.125 mg/kg/day)
Arm Description
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.
Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.0625 mg/kg/day dispensed per BID dosing, for 14 days.
Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.125 mg/kg/day dispensed per BID dosing, for 14 days.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Change From Baseline in Mean Volume at First Contraction
Average volume of urine collected by catheterization at first contraction.
Change From Baseline in Detrusor Pressure at First Contraction
Change From Baseline in Mean Volume at First Detectable Leakage
Average volume of urine collected by catheterization at first detectable leakage.
Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00712322
Brief Title
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
2. Study Status
Record Verification Date
September 2021
Overall Recruitment Status
Terminated
Why Stopped
Due to extremely difficult enrollment.
Study Start Date
October 7, 2008 (Actual)
Primary Completion Date
May 23, 2013 (Actual)
Study Completion Date
May 23, 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Warner Chilcott
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Neurogenic Detrusor Overactivity
Keywords
Pediatric, Children, Urodynamics, Oral Suspension, Overactive bladder, Dose-finding, Neurogenic Detrusor Overactivity, Meningomyelocele, Spinal cord injury
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1 (Darifenacin 0.030 mg/kg/day)
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 2 (Darifenacin 0.0625 mg/kg/day)
Arm Type
Experimental
Arm Description
Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.0625 mg/kg/day dispensed per BID dosing, for 14 days.
Arm Title
Cohort 3 (Darifenacin 0.125 mg/kg/day)
Arm Type
Experimental
Arm Description
Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.125 mg/kg/day dispensed per BID dosing, for 14 days.
Intervention Type
Drug
Intervention Name(s)
Darifenacin
Other Intervention Name(s)
Enablex®, Emselex®, DAR328
Intervention Description
Following a 7-day washout period, participants received darifenacin liquid oral suspension up to 14 days.
Primary Outcome Measure Information:
Title
Change From Baseline in Mean Maximum Bladder Capacity (MBC)
Description
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.
Time Frame
Baseline (Day 0) to Day 14
Secondary Outcome Measure Information:
Title
Change From Baseline in Mean Volume at First Contraction
Description
Average volume of urine collected by catheterization at first contraction.
Time Frame
Baseline (Day 0) to Day 14
Title
Change From Baseline in Detrusor Pressure at First Contraction
Time Frame
Baseline (Day 0) to Day 14
Title
Change From Baseline in Mean Volume at First Detectable Leakage
Description
Average volume of urine collected by catheterization at first detectable leakage.
Time Frame
Baseline (Day 0) to Day 14
Title
Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure
Time Frame
Baseline (Day 0) to Day 14
Title
Change From Baseline in Mean Catheterization Volume
Description
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.
Time Frame
Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14
Title
Change From Baseline in Total Pad Weight In-between Catheterizations
Description
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.
Time Frame
Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14
Title
Change From Baseline in Mean Catheterization Volume at First Awakening
Description
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.
Time Frame
Baseline (Day -1) to 2 consecutive days during the week prior to final study Day 14
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
15 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Herman Ellman, MD
Organizational Affiliation
Warner Chilcott (US) LLC
Official's Role
Study Director
Facility Information:
Facility Name
University of California at San Diego
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Children's Hospital, Karp 8210
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Children's Hospital of Michigan
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201-2119
Country
United States
Facility Name
Washington University Pediatric Urology
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Pediatric Urology Associates, PC
City
Lake Success
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
Pediatric Urology Associates PC
City
Tarrytown
State/Province
New York
ZIP/Postal Code
10591
Country
United States
Facility Name
Pediatric & Adolescent Urology, Inc Akron Children's Hospital
City
Akron
State/Province
Ohio
ZIP/Postal Code
44302
Country
United States
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Oregon Health & Science University
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
Fundacion Hospital Infantil, Universitario De San Jose
City
Bogota
Country
Colombia
Facility Name
Fundación Valle de Lili
City
Cali
Country
Colombia
Facility Name
Hospital Pablo Tobon Uribe
City
Medellín
Country
Colombia
12. IPD Sharing Statement
Learn more about this trial
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
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