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

NCT00712322 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: CDAR328B2201
• Study Type: interventional
• Target: 35
• Locations: 2 countries
• Sites: 12

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.

Conditions

Neurogenic Detrusor Overactivity

Keywords

Pediatric, Children, Urodynamics, Oral Suspension, Overactive bladder, Dose-finding, Neurogenic Detrusor Overactivity, Meningomyelocele, Spinal cord injury

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Change From Baseline in Mean Volume at First Contraction

  Baseline (Day 0) to Day 14

• Change From Baseline in Detrusor Pressure at First Contraction

  Baseline (Day 0) to Day 14

• Change From Baseline in Mean Volume at First Detectable Leakage

  Baseline (Day 0) to Day 14

• Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure

  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

Study Arms (3)

Cohort 1 (Darifenacin 0.030 mg/kg/day)

EXPERIMENTAL

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.

Drug: Darifenacin

Cohort 2 (Darifenacin 0.0625 mg/kg/day)

EXPERIMENTAL

Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.0625 mg/kg/day dispensed per BID dosing, for 14 days.

Drug: Darifenacin

Cohort 3 (Darifenacin 0.125 mg/kg/day)

EXPERIMENTAL

Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.125 mg/kg/day dispensed per BID dosing, for 14 days.

Drug: Darifenacin

Interventions

Darifenacin DRUG

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

Also known as: Enablex®, Emselex®, DAR328

Cohort 1 (Darifenacin 0.030 mg/kg/day); Cohort 2 (Darifenacin 0.0625 mg/kg/day); Cohort 3 (Darifenacin 0.125 mg/kg/day)

Eligibility Criteria

• Age: 2 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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
• Female adolescent of child-bearing potential, unless using an acceptable method of contraception

Sponsors & Collaborators

• Warner Chilcott: lead

Study Sites (12)

University of California at San Diego

San Diego, California, 92123, United States

Location

Children's Hospital, Karp 8210

Boston, Massachusetts, 02115, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201-2119, United States

Location

Washington University Pediatric Urology

St Louis, Missouri, 63110, United States

Location

Pediatric Urology Associates, PC

Lake Success, New York, 11042, United States

Location

Pediatric Urology Associates PC

Tarrytown, New York, 10591, United States

Location

Pediatric & Adolescent Urology, Inc Akron Children's Hospital

Akron, Ohio, 44302, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

Fundacion Hospital Infantil, Universitario De San Jose

Bogotá, Colombia

Location

Fundación Valle de Lili

Cali, Colombia

Location

Hospital Pablo Tobon Uribe

Medellín, Colombia

Location

MeSH Terms

Conditions

Urinary Bladder, Overactive; Meningomyelocele; Spinal Cord Injuries

Interventions

darifenacin

Condition Hierarchy (Ancestors)

Urinary Bladder Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neural Tube Defects; Nervous System Malformations; Nervous System Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Spinal Cord Diseases; Central Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries

Results Point of Contact

• Title: Therapeutic Area, Head
• Organization: Allergan

clinicaltrials@allergan.com

714-246-4500

Study Officials

• Herman Ellman, MD

  Warner Chilcott (US) LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 3, 2008
• First Posted: July 9, 2008
• Study Start: October 7, 2008
• Primary Completion: May 23, 2013
• Study Completion: May 23, 2013
• Last Updated: June 9, 2022
• Results First Posted: June 9, 2022

Record last verified: 2021-09

Locations

CO (3); US (9)