A multicenter, open-label, single ascending dose study to evaluate pharmacokinetics, safety and tolerability of solifenacin succinate suspension in pediatric patients aged 5 to 17 years (inclusive) with Overactive Bladder (OAB)Protocol for Phase I Study of solifenacin succinate suspensionSingle ascending dose PK study - GIRAFFE
- Conditions
- Overactive bladderMedDRA version: 12.1Level: LLTClassification code 10059617Term: Overactive bladder
- Registration Number
- EUCTR2009-017197-21-DK
- Lead Sponsor
- Astellas Pharma Europe B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 36
1. Symptoms of urgency, diagnosed as OAB according to International Children’s Continence Society (ICCS) criteria.
2. Daytime urgency incontinence at least once/day.
3. Patient is 5 to 11 (inclusive) or 12 to 17 (inclusive) years of age.
4. Weight and height are within normal age percentiles (3% to 97%) according to local country standards.
5. Patient and patient’s parent(s)/legal guardian are willing and able to comply with the study requirements and with the concomitant medication restrictions.
6. Informed consent (patient’s parent(s)/legal guardian) has been obtained; assent (patient) where appropriate is given.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
At screening:
1. Daytime voiding frequency less than 5.
2. Extraordinary daytime urinary frequency. Diagnosis according to ICCS definition:
• daytime voiding frequency is at least once hourly and
• average voided volumes are less than 50% of expected bladder capacity.
3. Uroflow indicative of pathology other than OAB.
4. Maximum voided volume > age expected capacity ([age +1] x 30) in ml.
5. PVR > 10% of the functional bladder capacity.
6. Monosymptomatic enuresis.
7. Polyuria.
8. Dysfunctional voiding.
9. Congenital anomalies of the genito-urinary tract or nervous system.
10. Current constipation (when treated the patient can enter the study).
11. Current urinary tract infection (patient will be eligible for enrolment 14 days after a negative dipstick test, provided a second dipstick test, performed after these 14 days, is also negative).
12. Kidney / bladder stones or other persistent local pathology that may cause urinary symptoms.
13. Urinary indwelling catheter within 4 weeks prior to study entry.
14. Patients with the following gastro-intestinal problems: partial or complete obstruction, decreased motility such as paralytic ileus, patients at risk of gastric retention.
15. Any clinically significant abnormality on physical examination.
16. Known history of QTc prolongation or risk of QT prolongation (e.g., hypokalemia,
family history of Long QT Syndrome [LQTS]).
17. Abnormal pulse rate (mean value) according to ranges specified below [Rijnbeek et al, 2001], judged as clinically significant by the investigator.
- age 5-7 years: <60 beats per minute (bpm) or >110 bpm
- age 8-11 years: <55 bpm or >100 bpm
- age 12-17 years: <50 bpm or >100 bpm
18. Mean systolic blood pressure greater than the 95th percentile according to age and height and/or greater than 140 mmHg, judged as clinically significant by the
investigator; mean diastolic blood pressure greater than the 95th percentile according to age and height and/or greater than 90 mmHg, judged as clinically significant by the investigator.
19. History or presence of any malignancy.
20. Any clinically significant unstable medical condition or disorder, which in the opinion of the investigator precludes the patient from participating in the study.
21. Serum creatinine more than or equal to 2 times the upper limit of normal (ULN).
22. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) more than or equal to 2 times ULN, or bilirubin more than or equal to 1.5 times ULN.
23. Any other clinically significant out of range results of urinalysis, biochemistry or
hematology.
24. Any clinically significant abnormality on ECG.
25. Patient is breastfeeding, pregnant or intends to become pregnant during the study. Patients of childbearing potential who are sexually active must practice a highly reliable method of birth control (these are methods with a failure quotient of <1% per year such as hormonal implants, injectable contraceptives, oral contraceptives of combination type, intra-uterine pessaries restricted to hormone contraceptive coil, sexual abstinence or vasectomy of the partner). Note: the pregnancy test (ß-HCG in serum) at screening, which is to be performed in females of childbearing potential, needs to be negative.
26. Patient has participated in another clinical trial and/or has taken an investigational drug within 30 days (or 5 half-lives of the drug, or the limit set by national law, whichever is longer) prior to Day 1.
At Day 1:
33. Consumption of grapefruit, grap
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the PK of solifenacin succinate suspension after single-dose administration at different dose levels in children and adolescents with OAB.;Secondary Objective: To evaluate the safety and tolerability of solifenacin succinate suspension after single-dose administration at different dose levels in children and adolescents with OAB.;Primary end point(s): Pharmacokinetic variables:<br>• Maximum concentration (Cmax)<br>• Time to attain Cmax (tmax)<br>• Area under the plasma concentration – time curve (AUC) from time of dosing until last measurable concentration (AUClast)<br>• AUC extrapolated until time is infinity (AUCinf)<br>• Apparent terminal elimination half-life (t1/2)<br>• Apparent Total Body Clearance (CL/F)<br>• Apparent volume of distribution during the terminal phases (Vz/F)
- Secondary Outcome Measures
Name Time Method