Neurogenic Detrusor Overactivity, Overactive Bladder
Conditions
Keywords
Study of fesoterodine in pediatric overactive bladder patients
Brief summary
The purpose of the study is to evaluate the pharmacokinetics, safety, and tolerability of fesoterodine following administration to pediatric patients, aged 8-17 years, with overactive bladder.
Interventions
DRUGFesoterodine
4 mg once daily for Weeks 1-4 and 8 mg once daily for Weeks 5-8
Sponsors
Pfizer
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* A total body weight \>25 kg (55 lbs). * Symptoms of urinary frequency (average ≥8 daily bathroom visits to urinate) and urgency to urinate, with or without urgency incontinence, for at least 6 months prior to enrolment, OR * Stable neurological disease and urodynamically confirmed detrusor overactivity, who may require intermittent catheterization for management of urinary drainage.
Exclusion criteria
* Treatment with an investigational drug within 4 weeks or 5 half-lives, whichever is longer, before first study dose * Ongoing use of potent CYP3A4 inhibitors or inducers or CYP2D6 inhibitors * Ongoing use of another drug for treating overactive bladder * Uncontrolled narrow angle glaucoma, urinary or gastric retention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Apparent Oral Clearance (CL/F) | Day 28 and Day 56 | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated using non linear mixed effect modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. |
| Absorption Rate Constant (Ka) | Day 28 and Day 56 | — |
| Apparent Volume of Distribution (VC/F) | Day 28 and Day 56 | The volume necessary to account for the total amount of drug in the body if it were present throughout the body at the same concentration found in the blood. Estimated using non linear mixed effect modeling. |
| Area Under the Plasma Drug Concentration Time Curve (AUC) | Day 28 and Day 56 | AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption. |
| Maximum Observed Plasma Concentration (Cmax) | Day 28 and Day 56 | — |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) | Day 28 and Day 56 | — |
| Plasma Decay Half-Life (t1/2) | Day 28 and Day 56 | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Post-void Residual (PVR) Volume | Baseline, Week 4, and Week 8 post-dose | Volume of urine remaining in the bladder immediately after urination. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fesoterodine Fesoterodine 4 milligram (mg) tablet once daily (QD) from Baseline to Week 4, escalated to 8 mg tablet QD for Weeks 5 to 8. | 21 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Baseline to Week 4 | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Fesoterodine |
|---|---|
| Age Continuous | 13.1 years STANDARD_DEVIATION 2.7 |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 21 | 13 / 20 |
| serious Total, serious adverse events | 0 / 21 | 1 / 20 |
Outcome results
Primary
Absorption Rate Constant (Ka)
Time frame: Day 28 and Day 56
Population: Pharmacokinetic (PK) concentration population: randomized and treated participants who had at least 1 concentration during the study.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Fesoterodine | Absorption Rate Constant (Ka) | 0.44 1/hour (hr) |
Primary
Apparent Oral Clearance (CL/F)
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated using non linear mixed effect modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.
Time frame: Day 28 and Day 56
Population: PK Concentration
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Fesoterodine | Apparent Oral Clearance (CL/F) | 86.70 L/hr |
Primary
Apparent Volume of Distribution (VC/F)
The volume necessary to account for the total amount of drug in the body if it were present throughout the body at the same concentration found in the blood. Estimated using non linear mixed effect modeling.
Time frame: Day 28 and Day 56
Population: PK Concentration
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Fesoterodine | Apparent Volume of Distribution (VC/F) | 1010.00 Liters (L) |
Primary
Area Under the Plasma Drug Concentration Time Curve (AUC)
AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Time frame: Day 28 and Day 56
Population: Not analyzed due to the limited amount of data available.
Primary
Maximum Observed Plasma Concentration (Cmax)
Time frame: Day 28 and Day 56
Population: Not analyzed due to the limited amount of data available.
Primary
Plasma Decay Half-Life (t1/2)
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
Time frame: Day 28 and Day 56
Population: Not analyzed due to the limited amount of data available.
Primary
Time to Reach Maximum Observed Plasma Concentration (Tmax)
Time frame: Day 28 and Day 56
Population: Not analyzed due to the limited amount of data available.
Secondary
Post-void Residual (PVR) Volume
Volume of urine remaining in the bladder immediately after urination.
Time frame: Baseline, Week 4, and Week 8 post-dose
Population: Safety Population: all participants who were known to have received study medication; Number of participants analyzed (N) = participants not performing clean intermittent bladder catheterization (CIC); n = participants not performing CIC at specified time point.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Fesoterodine | Post-void Residual (PVR) Volume | Baseline (n=10) | 6.00 mL |
| Fesoterodine | Post-void Residual (PVR) Volume | Week 4 (n=12) | 4.00 mL |
| Fesoterodine | Post-void Residual (PVR) Volume | Week 8 (n=8) | 25.00 mL |