Overactive bladder MedDRA version: 12.0 Level: LLT Classification code 10059617 Term: Overactive bladder
Conditions
Interventions
Trade Name: Vesicare
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SOLIFENACIN
CAS Number: 242478-38-2
Current Sponsor code: YM905
Other descriptive name: SOLIFENACIN SUCCINATE
Concentr
Sponsors
Astellas Pharma Europe Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subject is eligible for the study if all of the following apply: 1. The subject should be female aged greater than or equal to 18 years of age. 2. The subject should have symptoms of overactive bladder (OAB), including urinary frequency, urgency or urge incontinence, for greater than or equal to 3 months. 3. The subject should have an urodynamic diagnosis of detrusor overactivity (DO). 4. The subject should be either naïve to anti-muscarinic treatment (i.e. no prior history of use of antimuscarinic agents) or 6-months anti-muscarinic treatment free i.e. have had no anti-muscarinic treatment within 6 months) prior to the screening visit. 5. The subject should have a bladder post-void residual volume of less than 30ml. 6. The subject has provided Independent Ethics Committee (IEC)-approved written informed consent and privacy language as per national regulations (e.g., HIPAA Authorization for U.S. sites) prior to any study-related procedures. 7. The subject is available to complete the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subject will be excluded from participation if any of the following apply: 1. The subject has a history of stress urinary incontinence, uretheral sphincter incompetence or neurogenic detrusor overactivity. 2. The subject has a history, signs or symptoms suggestive of urinary tract infection (confirmed by positive urine analysis), obstruction or urogenital pro-lapse (greater than grade II). 3. The subject has a history of urinary tract operation within 6 months prior to screening. 4. The subject has an indwelling catheter or permanent catheter fitted. 5. The subject has a history of pelvic area radiotherapy treatment. 6. The subject has uncontrolled diabetes mellitus. 7. The subject has a history of fibromyalgia. 8. The subject is post-partum or breast-feeding within 3 months prior to screening visit. 9. The subject is either pregnant or intends to become pregnant during the study or sexually active, of childbearing potential and is unwilling to utilize a reliable method of birth control such as implants, injectables, combined oral contraceptives, some IUDs sexual abstinence or vasectomized partner. 10. The subject has a positive pre–study hepatitis B surface antigen, hepatitis C antibody or HIV result at time of screening. 11. The subject has a history of drug and / or alcohol abuse at time of screening. 12. The subject has a history of known or suspected hypersensitivity to solifenacin succinate, oxybutynin hydrochloride, other anti-cholinergics or lactose, to any component of the dosage form or any other allergy, which, in the opinion of the Investigator, contraindicates their participation. 13. The subject has a history of urinary retention, severe gastrointestinal obstruction (including paralytic ileus or intestinal atony or toxic megacolon or severe ulcerative colitis), myasthenia gravis, uncontrolled narrow angle glaucoma or shallow anterior chamber or deemed to be at risk for these conditions. 14. The subject is undergoing hemodialysis or has severe renal impairment (creatinine clearance =< 30 ml/ min) or moderate hepatic impairment. Subjects who are on treatment with a potent CYP3A4 inhibitor, e.g. Ketoconazole will also be excluded. (Prior to randomization at least one actual serum creatinine value should be available to calculate creatinine clearance according to MDRD / Cockroft Gault.) 15. The subject has started or had any dose(s) changes of medication, described in the list in appendix 1B (list of medications permitted with restrictions), within 1 month prior to screening, which will interfere with the study procedures or compromise safety. 16. The subject is currently dosing with medication(s) intended to treat overactive bladder symptoms or has a history of non-drug treatment, such as electrical therapy, magnetic field stimulation, pelvic floor treatment or bladder training intended to treat overactive bladder symptoms within 6 months prior to screening, as described in the list in appendix 1A (list of prohibited medications). 17. The subject is currently receiving or has a history of treatment with alpha blockers, botulinum toxin (cosmetic use is acceptable), resiniferatoxin or pelvic floor muscle relaxants within 9 months prior to screening, as described in the list in appendix 1A (list of prohibited medications) 18. The subject has any clinically significant abnormality following Investigator review of the physical examination which, in the opinion of the Investigator, contraindicates her participation. 19
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate the effect of solifenacin versus placebo on bladder wall thickness (BWT) after 12 weeks of treatment. 2. To evaluate the effect of solifenacin versus placebo on urinary Nerve Growth Factor (uNGF) normalized by urine creatinine level (uNGF/Cr) after 12 weeks of treatment in subjects with uNGF above laboratory quantification limit at baseline.;Secondary Objective: 1. To evaluate the effect on bladder wall thickness (BWT) of a. Solifenacin versus placebo after six (6) weeks of treatment. b. 5mg and 10mg of solifenacin (dose response). 2. To evaluate the relationship of bladder wall thickness (BWT) and a. OAB symptoms at baseline and changes observed during the study. b. Changes observed in subject perceived satisfaction scales. 3. To evaluate the effect on urinary nerve growth factor (uNGF) / creatinine (Cr) of a. Solifenacin versus placebo after six (6) weeks of treatment. b. 5mg and 10mg of solifenacin (dose response). 4. To evaluate the relationship of urinary nerve growth factor (uNGF) / creatinine (Cr) and a. OAB symptoms at baseline and changes observed during the study. b. Changes observed in subject perceived satisfaction scales. 5. To evaluate the relationship between bladder wall thickness (BWT) and urinary nerve growth factor (uNGF) / creatinine (Cr). 6. To evaluate the safety and tolerability of 5mg and 10mg solifenacin.;Primary end point(s): 1. Change from baseline to week 12 LOCF in bladder wall thickness measured with TVUS. 2. Value at week 12 LOCF in urinary nerve growth factor / creatinine. | — |
Countries
Austria, Belgium, Bulgaria, Czech Republic, France, Germany, Hungary, Italy, Slovakia, Spain, Sweden, United Kingdom
Outcome results
None listed