AURA-2: Augmenting Urinary Reflex Activity

Inclusion Criteria:

• Female patients aged ≥ 18 years

• Diagnosis of urinary incontinence, with on a 5-day voiding diary at least 1 dailyurgency episode and/or greater than or equal to 8 voids/day and/or by having aminimum of two involuntary leaking episodes in 72 hr

• Duration of urinary incontinence symptom ≥ 6 months prior to the screening baselinevisit date

• Failed or is not a candidate for more conservative treatment e.g. pelvic floormuscle therapy or biofeedback or behavioral modification

• Failed or could not tolerate at least one (1) antimuscarinic or beta3-adrenoceptoragonist medication

• Urodynamic testing (uroflowmetry, cystometry and pressure flow) completed within 12months prior to screening baseline visit date or is willing to have testing atscreening baseline visit

• Cystoscopy test completed within 12 months prior to the screening baseline visitdate or is willing to have a test at screening baseline visit

• Is willing and able to washout from OAB medications for at least 4 week prior tobeginning the baseline voiding diary

• Ability and willingness to give informed consent including language constraints (seeabove)

• Able to participate in all testing and follow-up clinic visits associated with studyprotocol

• Capable of independently using the system components (after training) as describedin the Patient Manual

• Mobile and able to use toilet without assistance

Exclusion Criteria:

General:

• Patient is pregnant, breastfeeding, or plans to become pregnant during the course ofthe study (pregnancy tests provided in schedule)

• Patient is unwilling or unable to use contraception during sexual intercourse forthe duration of the study, and thereafter if implant remains in the longer term.

• Any significant medical condition that is likely to interfere with study procedures,device operation, or likely to confound evaluation of study endpoints

• Any psychiatric or personality disorder at the discretion of the study physician

• Any neurological condition that may interfere with normal bladder function (e.g.,stroke, multiple sclerosis, Parkinson's disease; clinically significant peripheralneuropathy, or complete spinal cord injury)

• Patient has uncontrolled type I or type II diabetes as defined by their routine careclinician or diabetes with peripheral nerve involvement

• Any history of any pelvic cancer

• Patient has history of other non-pelvic neoplasia within 5 years prior to enrolment,except for a cancer that was determined to be local occurrence only, such as basalcell carcinoma, or is receiving or planning to receive anti-cancer oranti-angiogenic drugs

• Patient has proven major autoimmune disease, e.g. scleroderma or immunodeficiency (including use of biologic immunomodulatory drugs at time of procedure)

• Life expectancy of less than 1 year

• Patient is a frail elderly and/or with notable clinical evidence of sarcopaenia

• Patient is not suitable for the study as determined by their routine care physicianfor any other reason

• Patient is enrolled in another interventional study excepting observational studies,e.g. SNM registries or in relation to disease (see below)

• Patient participation in vigorous sporting activities where these cannot berestricted for a period of 6 weeks post-implantation.

Specific urological

• Urinary tract mechanical obstruction such as urethral stricture

• Current symptomatic urinary tract infection (UTI) or more than 3 UTIs in past year

• Pure stress incontinence or mixed incontinence where the stress component overridesthe urge component

• Interstitial cystitis or bladder pain syndrome as defined by either AUA or EAUguidelines

• Suspected pudendal nerve entrapment syndrome. In patients with co-existent symptomsof chronic pelvic pain and urinary incontinence, Nantes criteria will be used forscreening. Patients meeting essential criteria will be excluded from the study

• Treatment of urinary symptoms with botulinum toxin therapy in the past 12 months

• Prior attempt at pudendal nerve stimulation using an implanted lead

• Treatment of urinary symptoms with tibial or sacral nerve stimulation in the past 3months (prior experience of either before this time is permitted provided noimplants remain in-situ)

Specific technical

• Patient is significantly obese (defined as BMI ≥ 35) so as to limit electrode leadplacement using standard approaches

• Skin, orthopaedic or neurological anatomical limitations that could preventsuccessful placement of the electrode lead

• Knowledge of planned MRIs, diathermy, microwave exposure, high output ultrasonicexposure, or RF energy exposure

• Implantable neurostimulator, pacemaker or defibrillator in situ (anywhere in bodyincluding sacral and tibial)

• Subject with a documented history of allergic response to titanium, zirconia,polyurethane, epoxy, or silicone