CAN-Stim Compared to SNS in Treatment of Urinary Urgency Incontinence With Wireless Neuromodulation Technology

Subjects will be randomized at baseline to either CAN-Stim or SNS InterStim® after inclusion
and exclusion criteria have been met, 150 subjects will be randomized in to either arm of the
study (89 subjects each arm).

At the following visit, CAN-Stim subjects will be immediately implanted unilaterally with a
permanent device (implantation side up to investigators discretion). During implantation, the
subject should feel pulsation in their foot with or without toe flexion, confirming
stimulation of the tibial nerve. Subjects not achieving this motor response will not have the
device implanted and will be exited from the study. Implanted subjects will be educated on
the use of the transmitter and programmer. Programming parameters will be set and therapy
will be delivered for a minimum of 8 hours per day for 2 weeks. Programming changes can be
done as needed during this time period to maximize clinical response. At the 2-week visit,
diaries will be reviewed and confirmed for accuracy and discrepancies and the number of
urgency incontinence episodes will be calculated and compared to baseline diaries. Subjects
who are considered a responder at the 2-week follow-up visit (>50% improvement in urgency
related incontinence episodes) will continue therapy and followed for a total of 12 months
with primary outcomes assessed at 3 months. Non-responders will be offered an explant of the
device and will exit the study. Subjects having less than 50% improvement may choose to keep
the device. These subjects will be followed for adverse events with phone calls at 3, 6 and
12 months.

Subjects randomized to SNS will have their Stage I device implanted and tested during a
2-week period. Stage I will have a tined, quadripolar lead placed in the S3 (preferred) or S4
(alternate) foramen in the standard fashion using fluoroscopic guidance and motor response.
Motor responses can include a contraction of the levators ("bellows" response) with or
without plantar flexion of the great toe. Subjects who are not demonstrating an appropriate
motor response will not have the device implanted and will be exited from the study.
Subjects, who respond intraoperatively, will have the extension lead connected and
externalized in the standard fashion. Subjects may have their InterStim® activated 24
hours/day, but a minimum of 8 hours per day for 2 weeks is required to remain in the study.
Programming changes can be done as needed during this time period to maximize the clinical
effect. At the 2-week visit, diaries will be reviewed and confirmed for accuracy and
clarified for discrepancies and the number of urgency incontinence episodes will be
calculated and compared to baseline diaries. Patients achieving a clinical response (>50%
improvement in urgency related incontinence episodes) will undergo implantation of a pulse
generator and removal of the percutaneous extension lead. The IPG will be programmed in the
standard fashion using settings that were working for the patient during the 2-week trial.
Subjects implanted with the InterStim® device will be monitored for a total of 12 months with
primary outcomes assessed at 3 months. Non-responders will be offered an explant of the
device and will exit the study. Subjects having less than 50% improvement may choose to keep
the device. These subjects will be followed for adverse events with phone calls at 3, 6 and
12 months.

Inclusion Criteria:

- Diagnosis of overactive bladder with urgency urinary incontinence or mixed
incontinence (urge and stress) with predominate urge, as confirmed by the MESA
questionnaire;

- Women and men ≥ 18 years of age;

- Women of child-bearing age willing to practice birth control;

- At least 4 incontinent episodes associated with urgency on a 3-day voiding diary;

- At least 10 voids per day;

- Average urgency score of at least 2 as measured with IUSS on a 3-day voiding diary;

- Self-reported bladder symptoms present > 6 months;

- Documented failure of an adequate trial of first and second line therapy;

- Off all antimuscarinics and beta-3 adrenergic agonists for at least 2 weeks prior to
enrollment;

- If on Tricyclic antidepressants, dosage must be stabilized for at least 3 months;

- Have no active urethral obstruction/stricture, bladder calculi or bladder tumor based
on medical history;

- Normal upper urinary tract function based on medical history;

- Based on the medical opinion of the Investigator, there is no evidence of anatomic
abnormalities that could jeopardize the placement of the device or pose a hazard to
the subject;

- Based on the medical opinion of the Investigator, subject is willing and able to
operate the patient programmer, recharging equipment, diary and has the ability to
undergo study assessments and provide accurate responses;

- Based on the medical opinion of the Investigator, subject is a good surgical subject
for the implant procedure;

- Capable of giving informed consent;

- Capable and willing to follow all study related procedures.

Exclusion Criteria:

- An active implantable electronic device regardless of whether stimulation is ON or
OFF;

- Pregnant as confirmed by a urine pregnancy test or plan to become pregnant during the
following 12 months period;

- Primary complaint of stress urinary incontinence;

- Less than 1 year post-partum and/or are breast-feeding;

- Neurogenic bladder (i.e. Multiple sclerosis, Parkinson's, Spinal Cord Injury);

- Patients with spinal hardware that would limit access to the sacrum;

- Botox use in bladder or pelvic floor muscles in the past nine months;

- Have a post-void residual urine volume >150 cc at baseline;

- Current urinary tract infection (UTI);

- Previous treatment with sacral neuromodulation;

- Previous treatment with percutaneous tibial nerve stimulation, pelvic floor muscle
stimulation, or biofeedback within the past 60 days;

- Conditions requiring Magnetic Resonance Imaging (MRI) evaluation or diathermy
procedures;

- Inability to operate the CAN-Stim System or InterStim System;

- Diabetes with peripheral nerve compromise or severe uncontrolled diabetes (HbA1C 8.5
or greater);

- History of coagulopathy or bleeding disorder;

- History of pelvic pain as primary diagnosis (VAS score of > 4) at baseline;

- Anatomical restrictions such that device placement is not possible;

- Are currently participating or have participated within the past 30 days in any
clinical investigation involving or impacting urinary or renal function;

- Have a life expectancy of less than 1 year;

- Cannot independently comprehend and complete the questionnaires and diaries;

- Deemed unsuitable for enrollment by the investigator based on history or physical
examination (including bleeding disorders or anticoagulant medications, and peripheral
neuropathy).