A Study Evaluating the Efficacy and Safety of BOTOX® and Solifenacin in Patients with Overactive Bladder and Urinary Incontinence

Phase 1

• Conditions: Overactive Bladder and Urinary Incontinence; MedDRA version: 17.1Level: LLTClassification code 10059617Term: Overactive bladderSystem Organ Class: 100000004857; Therapeutic area: Not possible to specify

• Registration Number: EUCTR2012-003255-11-DE
• Lead Sponsor: Allergan Limited

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-03-19
• Last Update Posted: 22 May 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 345

Inclusion Criteria

1. Patient is male or female, aged = 18 years old.

2. Patient weighs = 40 kg (88 lbs).

3. Patient has OAB and urinary incontinence for a period of at least 6 months immediately prior to screening, determined by documented patient history

4. Patient experiences = 3 episodes of urinary urgency incontinence, with no more than 1 urinary urgency incontinence-free day, in the 3-day patient bladder diary completed during the screening period (see Section 6.3.4 Bladder Diary).

5. Patient experiences urinary frequency, defined as an average of = 8 micturitions (toilet voids) per day ie, a total of = 24 micturitions in the 3-day patient bladder diary completed during the screening period (see Section 6.3.4 Bladder Diary).

6. Patient has not been adequately managed with one or more anticholinergic agent for treatment of their OAB symptoms, in the opinion of the investigator. Not adequately managed is defined as:
oan inadequate response after at least a documented 4-week period of anticholinergic therapy on an optimized dose(s) ie, patient was still incontinent despite anticholinergic therapy, or
olimiting side effects after at least a documented 2-week period of anticholinergic therapy on an optimized dose(s).
An optimized dose is defined as an approved dose for the indication of OAB

7. Patient is willing to use clean intermittent catheterization (CIC) to empty the bladder at any time after study treatment, if it is determined to be necessary by the investigator
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 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 145

Exclusion Criteria

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

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

3. Patient has had previous or current therapy for OAB with solifenacin (any dose).

4. patient has received anticholinergics or any other medications or therapies to treat symptoms of OAB, including nocturia, within 7 days of the start of the screening period procedures

5. Patient uses CIC or indwelling catheter to manage their urinary incontinence.

6. 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 randomization/day 1

7.Patient has had previous or current botulinum toxin therapy of any serotype for any urological condition (or for any other condition within 12 weeks of randomization/day 1).

8. Patient has a history or evidence of uncontrolled narrow-angle glaucoma.

9. Patient has received therapy with ketoconazole or other potent cytochrome P450 3A4 (CYP3A4) inhibitors, within 7 days of the start of the screening period procedures.

10. Patient has serum creatinine level > 2 times the upper limit of normal at screening.

11. Patient has liver function tests (bilirubin, aspartate aminotransferase [AST], alanine aminotransferase [ALT]) > 1.5 times the upper limit of normal at screening.

12. Patient has decreased gastrointestinal motility, in the opinion of the investigator.

13. Patient has a known hypersensitivity to solifenacin, one of its components, including lactose, or to any other anticholinergics

14. Patient has a history of congenital or acquired QT prolongation

15. patient has history or evidence of any pelvic or urological abnormalities, bladder surgery or disease, other than OAB, that may affect bladder function including but not limited to:
o bladder stones and/or bladder stone surgery at the time of screening or within 6 months prior to screening
o surgery (including minimally invasive surgery) within 1 year of screening for stress incontinence, uterine prolapse, rectocele, or cystocele
o current or planned use of an electrostimulation/neuromodulation device (including posterior tibial nerve stimulation) for treatment of urinary incontinence (if a device is still implanted it must be inactive 4 weeks prior to randomization/day 1 and for the duration of the study); use of other nonimplantable electrostimulatory devices are also exclusionary.

16. Patient has evidence of urethral and/or bladder outlet obstruction, in the opinion of the investigator at screening or randomization/day 1

17. Patient has a PVR urine volume of > 100 mL at screening. The PVR measurement can be repeated once; the patient is to be excluded if the repeated measure is above 100 mL.

18. 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 screening. Note: voiding difficulties as a result of surgical procedures that resolved within 24 hours are not exclusionary

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 efficacy and safety of intradetrusor BOTOX® 100 U compared to placebo in patients with OAB and urinary incontinence whose symptoms have not been adequately managed with anticholinergic therapy and are solifenacin naïve;Secondary Objective: To compare the treatment effects of BOTOX® and solifenacin.;Primary end point(s): There are 2 co-primary efficacy measures:<br>1. number of episodes of urinary incontinence as recorded by the patient in the 3-day bladder diary completed in the week prior to each study visit<br>2. proportion of patients who have 100% reduction (incontinence free/dry) from study baseline (ie, baseline prior to intradetrusor treatment 1) in urinary incontinence<br>;Timepoint(s) of evaluation of this end point: The primary timepoint is week 12 after intradetrusor treatment 1.<br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): The secondary measures include:<br>1. proportion of patients who have a positive treatment response on the Treatment Benefit Scale (TBS) (score of either 1 or 2, representing ‘greatly improved’ or ‘improved’)<br>2. number of micturition episodes<br>3. number of nocturia episodes (voids that interrupt night sleep)<br>4. mean KHQ domain scores for 2 of the 7 multi-item KHQ domains (‘Role Limitations’ and ‘Social Limitations’)<br>;Timepoint(s) of evaluation of this end point: The secondary end point timepoint is week 12 after intradetrusor treatment 1.