To evaluate the efficacy, safety and PK of solifenacin succinate suspension after multiple dose administration.
ID
Source
Brief title
Condition
- Neurological disorders NEC
- Bladder and bladder neck disorders (excl calculi)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change from baseline in maximum cystometric capacity (MCC) after 24 weeks of
treatment.
Secondary outcome
Those based on urodynamics are change from baseline to weeks 9 and/or 24 in:
* MCC (at week 9 only);
* Bladder compliance (*V/*Pdet);
* Bladder volume until first detrusor contraction (> 15 cmH2O);
* Bladder volume at 30 cm H2O detrusor pressure;
* Bladder volume at 40 cm H2O detrusor pressure;
* Number of overactive detrusor contractions (> 15 cmH2O) until leakage or
maximum 135% of age-related bladder capacity;
* Detrusor pressure at leakage or 135% of age-related cystometric capacity.
In addition, there is an optional urodynamic investigation at week 52. When
this is performed, the urodynamic parameters listed above will be recorded and
evaluated as secondary efficacy variables.
Those based on diary are:
* Change from baseline for visit 4 (week 3) to visit 10 (week 52) in:
o Average catheterized volume per catheterization;
o Maximum catheterized volume per day;
o Mean number of incontinence episodes per 24 hours;
o Number of dry (incontinence-free) days/7 days.
* Change from baseline to visit 8 (week 24) and visit 10 (Week 52) in:
o Quality of life.
Other efficacy data collected within the study for comparisons with historical
control data (in addition to published results from other studies): Average
catheterized volume per catheterization, maximum catheterized volume per day,
mean number of incontinence episodes per 24 hours, number of dry
(incontinence-free) days/7 days and quality of life data collected at start of
washout of previous antimuscarinic overactive bladder (OAB) medication.
Safety variables:
* Overall incidence and severity of adverse events;
* Change from baseline in vital signs (systolic and diastolic blood pressure,
pulse rate and temperature) for visit 4 (week 3) to visit 10 (week 52);
* Change from baseline to visit 8 (week 24) and visit 10 (week 52) in safety
laboratory parameters (Hematology, Chemistry, Urinalysis);
* Change from baseline to visit 7 (week 12), visit 8 (week 24) and visit 10
(week 52) in ECG assessments;
* Change from baseline to visit 10 (week 52) in renal ultrasound assessment and
creatinine clearance as an indicator for renal function;
* Change from baseline to visit 10 (week 52) in ocular accommodation testing;
* Change from baseline to visit 7 (week 12), visit 8 (week 24) and visit 10
(week 52) in cognitive function;
* Change from baseline to visit 7 (week 12), visit 8 (week 24) and visit 10
(week 52) in height and weight.
Other safety data collected within the study for comparisons with historical
control data (in addition to published results from other studies): Change
during washout in cognitive function for subjects previously treated with other
antimuscarinic therapy, i.e., oxybutynin.
Pharmacokinetic variables:
Plasma concentrations of solifenacin succinate will be used to derive the
following PK parameters: Cmax, tmax, AUCtau, Ctrough, t1/2, CL/F and V/F.
Background summary
The purpose of this research study is to investigate a medicine for the
treatment of symptoms of neurogenic detrusor overactivity (NDO) in children and
adolescent patients. The medicine tested in this study is called solifenacin
succinate. Solifenacin succinate as a tablet formulation (Vesicare®) is already
on the market for the treatment of symptoms of overactive bladder (OAB) in
adults. For the use in children and adolescent patients a new formulation of
solifenacin has been developed. The new formulation is a liquid that will be
taken by mouth.
This study will investigate the effect and safety of solifenacin suspension
over a 52-week period of daily treatment. The study will also investigate how
well solifenacin suspension is taken-up by the body and how long it stays in
the body during this time.
Study objective
To evaluate the efficacy, safety and PK of solifenacin succinate suspension
after multiple dose administration.
Study design
This is an Open-Label, Baseline-controlled, Multi-center, Sequential Dose
Titration Study to Assess the Efficacy, Safety, and Pharmacokinetics of
Solifenacin Succinate Suspension in Patients, from 5 to Less than 18 years of
Age with Neurogenic Detrusor Overactivity (NDO).
Intervention
Aqueous suspension containing 1 mg/ml solifenacin succinate
The initial dose administered in Cohort 1 will be the equivalent of 5 mg in
adults and will be administered once a day. This is a Pediatric Equivalent Dose
of 5 mg (PED5). Doses will be calculated per weight. The dose will be up- or
down-titrated to the equivalent of the doses of 2.5 mg, 5.0 mg, 7.5 mg and 10
mg in adults; PED2.5, PED5, PED7.5 and PED10 respectively, according to the
titration criteria described in section 5.1.2 and the Schedule of Assessments.
The starting dose and titration steps for Cohort 2 will be confirmed after
review of the safety data from the first 10 subjects who have completed week 12
of Cohort 1 by the DSMB.
Oral administration (via syringes) in the morning, with a glass of water
afterwards. Dosing requirements will be provided to subjects in a separate
document.
52 weeks
Study burden and risks
The study is due to last for up to 13 months (up to 56 weeks) during which the
patient will receive 12 months (up to 52 weeks) of continuous study medication.
They expect the patient to attend the study clinic on 10 separate occasions.
For most visits the patient will need to stay at the clinic for 2 to 3 hours
(with parent/guardian). At visits 1 and 3 it may take up to 4 hours to complete
all the assessments required. The patient will need to stay at the clinic (with
parent/guardian) even longer for visit 7, which happens 12 weeks after he/she
first receives the study medicine. The visit 7 will take most of the day to
complete.
Elisabethhof 19
Leiderdorp 2353 EW
NL
Elisabethhof 19
Leiderdorp 2353 EW
NL
Listed location countries
Age
Inclusion criteria
-Documented diagnosis of NDO, confirmed by urodynamics
-Practicing clean intermittent catheterization (CIC).
-Currently on treatment with an antimuscarinic drug
Exclusion criteria
-Known genitourinary condition (other than NDO) that may cause incontinence
-Bladder augmentation surgery.
-Current Faecal impaction.
-Electro - stimulation therapy within 2 weeks prior to screening and at any time during the study.
-Subjects with the following gastro-intestinal problems: partial or complete obstruction, decreased motility like paralytic ileus, subjects at risk of gastric retention.
-Reflux grade 3 to 5.
-Current UTI
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-000330-11-NL |
| ClinicalTrials.gov | NCT01565694 |
| CCMO | NL39130.091.12 |