Integrale Overactieve Blaas Clinical Trial in de klinische praktijk III.

1. Written informed consent has been obtained;

2. Written documentation has been obtained in accordance with local privacy requirements, where applicable;

3. Patient is male or female, aged between 18 and 75 years old (Amundsen 2005);

4. Patient weighs ≥ 40 kg;

5. Patient has symptoms of idiopathic OAB (frequency and urgency) with urinary incontinence immediately prior to qualification, determined by documented patient history;

6. Patient experiences a mean of 3 episodes of urinary urgency incontinence in the 3-day patient bladder diary completed during the qualification period (qualification day -14 to start treatment day 1);

7. Patient experiences urinary frequency, defined as an average of ≥ 8 micturitions (toilet voids) per day i.e. a total ≥ 24 micturitions in the 3-day patient micturition diary completed during the qualification period (qualification day -14 to start treatment day 1);

8. Patient has a negative pregnancy test result if female and of childbearing potential;

9. Patient has a negative urine dipstick reagent strip test at start treatment day 1 (for nitrites, blood and leukocyte esterase) and, in the investigator’s opinion, patient is asymptomatic for UTI on day of treatment;

10. Patient is able to complete study requirements including using the toilet without assistance, is able to collect volume voided per micturition measurements over a 24- hour period, complete micturition diaries and questionnaires, and attend all study visits in the opinion of the coordinating investigator.

OAB patients not eligible for SNS and botulinum toxin type A:

1. Residual urine after micturition > 100 cc determined using sonography or catheterisation;

2. Presence of urinary tract infection (UTI), determined using urinary sticks. (temporarely until UTI has been solved by antibiotics, then still potential candidate);

3. Patient has symptoms of overactive bladder due to any known neurological reason (eg, spinal cord injury, multiple sclerosis, cerebrovascular accident, Alzheimer’s disease, Parkinson’s disease, etc);

4. Patient has a predominance of stress incontinence in the opinion of the coordinating investigator, determined by patient history;

5. Patient has received anticholinergics or any other medications or pelvic physiotherapy or PTNS to treat symptoms of overactive bladder, including nocturia, within 3 months of start treatment day 1;

6. Patient uses chronic intermittent catheterisation (CIC) or indwelling catheter to manage his or her urinary incontinence;

7. Patient has been treated with any intravesical pharmacologic agent (eg, capsaicin, resiniferatoxine) within 12 months of start treatment day 1;

8. Patient has history or evidence of any pelvic or urological abnormalities, bladder surgery or disease, other than ‘overactive bladder’, that may affect bladder function including but not limited to:
bladder stones and/or bladder stone surgery at the time of qualification or within 6 months prior to qualification, surgery (including minimally invasive surgery) within 1 year of qualification for: stress incontinence, uterine prolapse, rectocele, or cystocele;

9. Patient has a history of interstitial cystitis/painful bladder syndrome, in the opinion of the coordinating investigator;

10. Patient has an active genital infection, other than genital warts, either concurrently or within 4 weeks prior to qualification;

11. Patient has a history or current diagnosis of bladder cancer or other urothelial malignancy, and/or has un-investigated suspicious urine cytology results. Suspicious urine cytology abnormalities require that urothelial malignancy is ruled out to the satisfaction of the investigator according to local site practice;

12. Patient is male with previous or current diagnosis of prostate cancer or a prostate specific antigen (PSA) level of > 10 ng/L at screening. Patients with a PSA level of ≥ 4 ng/L but ≤ 10 ng/L must have prostate cancer ruled out to the satisfaction of the investigator according to local site practice;

13. Patient has evidence of urethral and/or bladder outlet obstruction, in the opinion of the coordinating investigator at qualification or start treatment day 1;

14. Patient has had urinary retention or an elevated PVR urine volume that has been treated with an intervention (such as catheterization) within 6 months of qualification. Note: voiding difficulties as a result of surgical procedures that resolved within 24 hours are not exclusionary;

15. Patient has a 24-hour total volume of urine voided > 3000 mL, collected over 24 consecutive hours during the 3-day bladder diary collection period prior to treatment day 1;

16. Patient has a history of 2 or more urinary tract infections within 6 months of qualification;

17. Patient has a serum creatinine level > 2 times the upper limit of normal at qualification;

18. Patient has current or previous un-investigated hematuria. Patient with investigated hematuria may enter the study if urological/renal pathology has been ruled out to the satisfaction of the investigator;

19. Patient has hemophilia, or other clotting factor deficiencies, or disorders that cause bleeding diathesis;

20. Patient cannot withhold any antiplatelet, anticoagulant therapy or medications with anticoagulant effects for 3 days prior to start treatment day 1. Note: some medications may need to be withheld for > 3 days, per clinical judgment of the investigator;

21. Patient has a known allergy or sensitivity to any components of the study medication, such as the active ingredients botulinum toxin type A or the inactive ingredients human albumin and sodium chloride or has had a known allergic reaction to any other botulinum toxin product such as Myobloc®, Dysport® or Xeomin® (Allergan Pharmaceuticals 2010), or antibiotics to be used during the study;

22. Females who are pregnant, nursing or planning a pregnancy during the study or females of childbearing potential who are unable or unwilling to use a reliable form of contraception during the study;

23. Patient is currently participating in or has previously participated in another therapeutic study within 30 days of qualification (or longer if local requirements specify);

24. The urologist first preference is a treatment with anticholinergics/antimuscarinics;

25. Use of anticoagulant medications (eg, warfarin and other coumadin derivatives), antiplatelet
medications (eg, clopidogrel and aspirin [including low dose]) and any other medications
with anticoagulative effects (eg, non-steroidal anti-inflammatory drugs [NSAIDs]) within a period 3 days (or longer according to the clinical judgment of the ccordinating investigator) prior to any study treatment.