E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10059617 |
E.1.2 | Term | Overactive bladder |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the PK of solifenacin succinate suspension after single-dose administration at different dose levels in children and adolescents with OAB. |
|
E.2.2 | Secondary objectives of the trial |
To evaluate the safety and tolerability of solifenacin succinate suspension after single-dose administration at different dose levels in children and adolescents with OAB. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
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. |
|
E.4 | Principal exclusion criteria |
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 (β-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, grapefruit juice or grapefruit marmalade within 14 days prior to Day 1. 34. Positive drug screen test for drugs of abuse at Day 1. 35. Positive alcohol breath test at Day 1. 36. Use of prohibited prior and concomitant medication (refer to Appendix 1): • Anti-muscarinics, antidepressants, desmopressin or alpha-blockers within 14 days prior to Day 1. • Intravesical treatment with botulinum toxin (any history). • Potent cytochrome P450 (CYP) 3A4 inhibitors (e.g., ketoconazole), CYP3A4 substrates with higher affinity (e.g., verapamil, diltiazem), or potent CYP3A4 inducers (e.g., rifampicine, phenytoin, carbamazepine), including natural and herbal remedies (e.g., St. John’s Wort) within 14 days prior to Day 1. 37. Donation of blood or blood products within 3 months prior to Day 1.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Pharmacokinetic variables: • Maximum concentration (Cmax) • Time to attain Cmax (tmax) • Area under the plasma concentration – time curve (AUC) from time of dosing until last measurable concentration (AUClast) • AUC extrapolated until time is infinity (AUCinf) • Apparent terminal elimination half-life (t1/2) • Apparent Total Body Clearance (CL/F) • Apparent volume of distribution during the terminal phases (Vz/F) |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | Yes |
E.7.1.3.1 | Other trial type description |
Single dose PK in children and adolescents |
|
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |