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

• Sponsor: Warner Chilcott (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT00712322
• Collaborator: (none)
• Enrollment: 35
• Locations: 12
• Arms: 3
• Actual Duration (Months): 55.5
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Neurogenic Detrusor Overactivity	Drug: Darifenacin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 35 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Oct 7, 2008
• Actual Primary Completion Date: May 23, 2013
• Actual Study Completion Date: May 23, 2013

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: Darifenacin; Following a 7-day washout period, participants received darifenacin liquid oral suspension up to 14 days.; Other Names: Enablex®, Emselex®, DAR328
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.	Drug: Darifenacin; Following a 7-day washout period, participants received darifenacin liquid oral suspension up to 14 days.; Other Names: Enablex®, Emselex®, DAR328
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.	Drug: Darifenacin; Following a 7-day washout period, participants received darifenacin liquid oral suspension up to 14 days.; Other Names: Enablex®, Emselex®, DAR328

Outcome Measures

Primary Outcome Measures

1. 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

1. 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.

2. Change From Baseline in Detrusor Pressure at First Contraction [Baseline (Day 0) to Day 14]

3. 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.

4. Change From Baseline in Mean Volume at 10, 20, 30, and 40 cm H2O Detrusor Pressure [Baseline (Day 0) to Day 14]

5. 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.

6. 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.

7. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 15 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of California at San Diego	San Diego	California	United States	92123
2	Children's Hospital, Karp 8210	Boston	Massachusetts	United States	02115
3	Children's Hospital of Michigan	Detroit	Michigan	United States	48201-2119
4	Washington University Pediatric Urology	Saint Louis	Missouri	United States	63110
5	Pediatric Urology Associates, PC	Lake Success	New York	United States	11042
6	Pediatric Urology Associates PC	Tarrytown	New York	United States	10591
7	Pediatric & Adolescent Urology, Inc Akron Children's Hospital	Akron	Ohio	United States	44302
8	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
9	Oregon Health & Science University	Portland	Oregon	United States	97239
10	Fundacion Hospital Infantil, Universitario De San Jose	Bogota		Colombia
11	Fundación Valle de Lili	Cali		Colombia
12	Hospital Pablo Tobon Uribe	Medellín		Colombia

Sponsors and Collaborators

• Warner Chilcott

Investigators

• Study Director: Herman Ellman, MD, Warner Chilcott (US) LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Warner Chilcott
• ClinicalTrials.gov Identifier: NCT00712322
• Other Study ID Numbers: CDAR328B2201
• First Posted: Jul 9, 2008
• Last Update Posted: Jun 9, 2022
• Last Verified: Sep 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Warner Chilcott: Pediatric, Children, Urodynamics, Oral Suspension, Overactive bladder, Dose-finding, Neurogenic Detrusor Overactivity, Meningomyelocele, Spinal cord injury
• Additional relevant MeSH terms: Urinary Bladder, Overactive; Darifenacin

Study Results

Participant Flow

Arm/Group Title	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/Group 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.
Period Title: Overall Study
STARTED	12	14	9
COMPLETED	12	13	9
NOT COMPLETED	0	1	0

Baseline Characteristics

Arm/Group Title	Cohort 1 (Darifenacin 0.030 mg/kg/Day)	Cohort 2 (Darifenacin 0.0625 mg/kg/Day)	Cohort 3 (Darifenacin 0.125 mg/kg/Day)	Total
Arm/Group Description	Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.030 mg/kg/day dispensed per 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.	Total of all reporting groups
Overall Participants	12	14	9	35
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.2 (3.0)	8.1 (3.2)	7.3 (3.1)	8.3 (3.1)
Sex: Female, Male (Count of Participants)
Female	3 25%	8 57.1%	5 55.6%	16 45.7%
Male	9 75%	6 42.9%	4 44.4%	19 54.3%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Per-protocol Population included all participants in the Safety Population who completed the study under treatment without major protocol deviation.

Arm/Group Title	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/Group Description	Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.030 mg/kg/day dispensed per 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.
Measure Participants	10	11	9
Baseline	180.21 (126.88)	142.18 (104.49)	165.89 (123.74)
Change From Baseline to Day 14	-36.58 (93.59)	-14.64 (48.40)	19.33 (76.12)

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Per-protocol Population included all participants in the Safety Population who completed the study under treatment without major protocol deviation. Number analyzed is the number of participants with available data at the given time point.

Arm/Group Title	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/Group Description	Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.030 mg/kg/day dispensed per 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.
Measure Participants	9	11	8
Baseline	85.09 (71.65)	56.91 (64.04)	63.94 (51.38)
Change From Baseline to Day 14	-2.17 (62.79)	14.00 (86.43)	22.13 (85.53)

3. Secondary Outcome

Title	Change From Baseline in Detrusor Pressure at First Contraction
Time Frame	Baseline (Day 0) to Day 14

Outcome Measure Data

Analysis Population Description

Per-protocol Population included all participants in the Safety Population who completed the study under treatment without major protocol deviation. Number analyzed is the number of participants with available data at the given time point.

Arm/Group Title	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/Group Description	Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.030 mg/kg/day dispensed per 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.
Measure Participants	9	11	8
Baseline	32.71 (43.35)	16.36 (10.62)	23.56 (19.25)
Change From Baseline to Day 14	-0.30 (13.85)	0.36 (17.63)	0.38 (16.86)

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Per-protocol Population included all participants in the Safety Population who completed the study under treatment without major protocol deviation. Number analyzed is the number of participants with available data at the given time point.

Arm/Group Title	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/Group Description	Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.030 mg/kg/day dispensed per 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.
Measure Participants	8	10	5
Baseline	151.25 (93.37)	107.50 (117.50)	113.70 (70.26)
Change From Baseline to Day 14	26.40 (48.37)	-29.50 (67.40)	-31.40 (96.26)

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Per-protocol Population included all participants in the Safety Population who completed the study under treatment without major protocol deviation. Number analyzed is the number of participants with available data at the given time point.

Arm/Group Title	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/Group Description	Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.030 mg/kg/day dispensed per 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.
Measure Participants	10	11	9
Baseline at 10 cm H2O	58.58 (48.60)	59.55 (49.98)	83.71 (89.32)
Change from Baseline to Day 14 at 10 cm H2O	13.48 (94.96)	0.27 (46.06)	23.14 (91.69)
Baseline at 20 cm H2O	85.30 (73.75)	83.00 (69.81)	106.60 (66.77)
Change from Baseline to Day 14 at 20 cm H2O	-14.28 (65.95)	-3.11 (48.41)	-14.80 (71.48)
Baseline at 30 cm H2O	121.81 (84.56)	118.17 (111.80)	136.00 (98.77)
Change from Baseline to Day 14 at 30 cm H2O	-9.09 (58.70)	-55.67 (101.26)	19.40 (94.69)
Baseline at 40 cm H2O	130.02 (92.57)	137.50 (126.04)	116.67 (90.64)
Change from Baseline to Day 14 at 40 cm H2O	-42.30 (56.14)	-55.17 (106.36)	-89.67 (91.72)

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Per-protocol Population included all participants in the Safety Population who completed the study under treatment without major protocol deviation. Number analyzed is the number of participants with available data at the given time point.

Arm/Group Title	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/Group Description	Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.030 mg/kg/day dispensed per 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.
Measure Participants	9	8	8
Baseline	93.57 (64.18)	65.98 (56.32)	115.18 (71.64)
Change From Baseline to Day 14	14.36 (44.68)	5.36 (24.17)	-5.50 (30.03)

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Per-protocol Population included all participants in the Safety Population who completed the study under treatment without major protocol deviation. Number analyzed is the number of participants with available data at the given time point.

Arm/Group Title	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/Group Description	Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.030 mg/kg/day dispensed per 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.
Measure Participants	7	8	8
Baseline	1428.157 (687.549)	764.250 (469.197)	690.875 (452.234)
Change From Baseline to Day 14	-274.786 (416.441)	289.000 (440.619)	38.125 (354.528)

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Per-protocol Population included all participants in the Safety Population who completed the study under treatment without major protocol deviation. Number analyzed is the number of participants with available data at the given time point.

Arm/Group Title	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/Group Description	Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.030 mg/kg/day dispensed per 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.
Measure Participants	9	8	8
Baseline	99.67 (61.14)	107.44 (104.58)	129.06 (69.40)
Change From Baseline to Day 14	47.94 (53.79)	23.69 (128.66)	-7.75 (51.49)

Adverse Events

Time Frame	From first dose of study drug to 30 days after the last dose of study drug (Up to 55 days)
Adverse Event Reporting Description	Safety Population included all participants in the Full Analysis Set who took at least 1 dose of darifenacin.
Arm/Group Title	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/Group Description	Following a 7-day washout period, participants received darifenacin liquid oral suspension, 0.030 mg/kg/day dispensed per 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.
All Cause Mortality
	Cohort 1 (Darifenacin 0.030 mg/kg/Day)		Cohort 2 (Darifenacin 0.0625 mg/kg/Day)		Cohort 3 (Darifenacin 0.125 mg/kg/Day)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/14 (0%)		0/9 (0%)
Serious Adverse Events
	Cohort 1 (Darifenacin 0.030 mg/kg/Day)		Cohort 2 (Darifenacin 0.0625 mg/kg/Day)		Cohort 3 (Darifenacin 0.125 mg/kg/Day)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/14 (0%)		1/9 (11.1%)
Infections and infestations
Urinary tract infection	0/12 (0%)		0/14 (0%)		1/9 (11.1%)
Other (Not Including Serious) Adverse Events
	Cohort 1 (Darifenacin 0.030 mg/kg/Day)		Cohort 2 (Darifenacin 0.0625 mg/kg/Day)		Cohort 3 (Darifenacin 0.125 mg/kg/Day)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/12 (50%)		6/14 (42.9%)		4/9 (44.4%)
Ear and labyrinth disorders
Vertigo	0/12 (0%)		2/14 (14.3%)		0/9 (0%)
Gastrointestinal disorders
Abdominal pain upper	1/12 (8.3%)		0/14 (0%)		0/9 (0%)
Constipation	0/12 (0%)		0/14 (0%)		2/9 (22.2%)
Dry mouth	0/12 (0%)		1/14 (7.1%)		0/9 (0%)
Infections and infestations
Nasopharyngitis	0/12 (0%)		1/14 (7.1%)		0/9 (0%)
Pyelonephritis	0/12 (0%)		1/14 (7.1%)		0/9 (0%)
Injury, poisoning and procedural complications
Urethral injury	0/12 (0%)		0/14 (0%)		1/9 (11.1%)
Contusion	1/12 (8.3%)		0/14 (0%)		0/9 (0%)
Fall	1/12 (8.3%)		0/14 (0%)		0/9 (0%)
Investigations
Body temperature increased	0/12 (0%)		1/14 (7.1%)		0/9 (0%)
Cardiac murmur	1/12 (8.3%)		0/14 (0%)		0/9 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/12 (0%)		1/14 (7.1%)		0/9 (0%)
Pain in extremity	1/12 (8.3%)		0/14 (0%)		0/9 (0%)
Nervous system disorders
Dizziness	1/12 (8.3%)		0/14 (0%)		0/9 (0%)
Headache	3/12 (25%)		0/14 (0%)		0/9 (0%)
Renal and urinary disorders
Urinary incontinence	0/12 (0%)		0/14 (0%)		1/9 (11.1%)
Renal pain	0/12 (0%)		1/14 (7.1%)		0/9 (0%)
Reproductive system and breast disorders
Dysmenorrhoea	1/12 (8.3%)		0/14 (0%)		0/9 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/12 (0%)		0/14 (0%)		1/9 (11.1%)
Rhinorrhoea	1/12 (8.3%)		0/14 (0%)		0/9 (0%)
Skin and subcutaneous tissue disorders
Rash	1/12 (8.3%)		1/14 (7.1%)		0/9 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

A disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 90 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.