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

Overview

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.

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Sequential Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: May 23, 2013

Interventions

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

Arms, Groups and Cohorts

  • Experimental: Cohort 1 (Darifenacin 0.030 mg/kg/day)
    • 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.
  • Experimental: Cohort 2 (Darifenacin 0.0625 mg/kg/day)
    • Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.0625 mg/kg/day dispensed per BID dosing, for 14 days.
  • Experimental: Cohort 3 (Darifenacin 0.125 mg/kg/day)
    • Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.125 mg/kg/day dispensed per BID dosing, for 14 days.

Clinical Trial Outcome Measures

Primary Measures

  • Change From Baseline in Mean Maximum Bladder Capacity (MBC)
    • Time Frame: 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 Measures

  • Change From Baseline in Mean Volume at First Contraction
    • Time Frame: Baseline (Day 0) to Day 14
    • Average volume of urine collected by catheterization at first contraction.
  • Change From Baseline in Detrusor Pressure at First Contraction
    • Time Frame: Baseline (Day 0) to Day 14
  • Change From Baseline in Mean Volume at First Detectable Leakage
    • Time Frame: Baseline (Day 0) to Day 14
    • 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
    • Time Frame: Baseline (Day 0) to Day 14
  • Change From Baseline in Mean Catheterization Volume
    • Time Frame: 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
    • Time Frame: 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 Catheterization Volume at First Awakening
    • Time Frame: 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.

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 2 Years

Maximum Age: 15 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Warner Chilcott
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Herman Ellman, MD, Study Director, Warner Chilcott (US) LLC

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