Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence
Phase: NA
Conditions: Urgency Urinary Incontinence
Sponsor: Valencia Technologies Corporation

Original Application for an 
Investigational Device Exemption 
19 July 2017
Subcutaneous Tibial Nerve Stimulation 
for Urgency Urinary Incontinence 
Device Name: 
 eCoin (Electroceutical Coin) 
Protocol Number: 
IDE Number: 
111-3186 
G170028
NCT03029624
Sponsor & Manufacturer: 
Valencia Technologies Corporation 
28464 Westinghouse Place 
Valencia, CA 91355 
United States 
Principal Investigators: 
Scott MacDiarmid, M.D. 
CONFIDENTIAL 
Document Number 111-3186 Rev. 1.6 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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Valencia Technologies Corporation          Doc. No. 111-3186 Rev. 1.6                         
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TABLE OF CONTENTS 
1 
INTRODUCTION ................................................................................................................................................ 5 
 
NAME, ADDRESS, AND SIGNATURE OF SPONSOR ..................................................................................................... 5 
 
OVERVIEW ...................................................................................................................................................................... 5 
2 
REPORT OF PRIOR INVESTIGATIONS ....................................................................................................... 7 
 
PRIOR PUBLICATIONS OF ANIMAL STUDIES .............................................................................................................. 7 
 
HUMAN STUDIES ........................................................................................................................................................... 8 
2-2-1 
Prior Publications of Tibial Nerve Stimulation for Overactive Bladder ......................................... 8 
2-2-2 
Prior Studies of the Valencia Technologies eCoin System .................................................................... 9 
 
EXECUTIVE SUMMARY OF NON-CLINICAL STUDIES............................................................................................... 11 
2-3-1 
Bench Testing - eCoin Device ........................................................................................................................ 11 
2-3-2 
Bench Testing External Controller ............................................................................................................. 15 
2-3-3 
MR Compatibility ............................................................................................................................................... 16 
2-3-4 
Electrical Safety and Electromagnetic Compatibility ......................................................................... 17 
2-3-5 
Electrical Safety and EMC External Controller ...................................................................................... 18 
2-3-6 
Software eCoin Device (209-1035, 209-1061, 303-1122) ................................................................. 18 
2-3-7 
Software External Controller (207-1541, 303-1122) .......................................................................... 18 
2-3-8 
Biocompatibility ................................................................................................................................................. 19 
2-3-9 
Particulate (Nelson Lab Number 884283-01) ....................................................................................... 21 
2-3-10 
Sterility (2002-1206) .................................................................................................................................. 21 
2-3-11 
Packaging (202-1254; Westpak 225-15-0053A) ............................................................................. 21 
2-3-12 
Shelf Life (202-1254; Westpak 225-15-0053B, 225-15-0053C) ................................................ 22 
3 
INVESTIGATIONAL PLAN ............................................................................................................................ 23 
 
PURPOSE ....................................................................................................................................................................... 23 
 
SUMMARY ..................................................................................................................................................................... 23 
 
PROTOCOL .................................................................................................................................................................... 24 
3-3-1 
Study Design ........................................................................................................................................................ 24 
3-3-2 
Subject Selection ................................................................................................................................................ 24 
3-3-3 
Ethical Considerations ..................................................................................................................................... 25 
 
STUDY PROCEDURES ................................................................................................................................................... 26 
3-4-1 
Subject Recruitment Plans ............................................................................................................................. 26 
3-4-2 
Visit Overview ..................................................................................................................................................... 27 
3-4-3 
Screening for Eligibility Procedures ........................................................................................................... 30 
3-4-4 
Prior and Concomitant Therapy .................................................................................................................. 30 
3-4-5 
Informed Consent Procedures ...................................................................................................................... 30 
3-4-6 
Baseline Visit Assessments ............................................................................................................................. 30 
3-4-7 
Implantation of Subcutaneous Neuromodulation System ................................................................ 31 
3-4-8 
eCoin Activation ................................................................................................................................................. 31 
3-4-9 
Establishment of the Electrical Regimen ................................................................................................. 31 
3-4-10 
Post Activation Follow-up Procedure................................................................................................... 32 
3-4-11 
Escape Procedure ......................................................................................................................................... 32 
 
STUDY ENDPOINTS ...................................................................................................................................................... 32 
3-5-1 
Primary Outcome Measures .......................................................................................................................... 32 
3-5-2 
Key Secondary Outcome Measure ............................................................................................................... 32 
3-5-3 
Exploratory Secondary Outcome Measures ............................................................................................ 32 
 
RATIONALE FOR THE SELECTION OF OUTCOME MEASURES AND STUDY DESIGN ............................................ 33 
 
RISK ANALYSIS............................................................................................................................................................. 34 
3-7-1 
Overview................................................................................................................................................................ 34 
3-7-2 
Description of Patient Population ............................................................................................................... 35 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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Valencia Technologies Corporation          Doc. No. 111-3186 Rev. 1.6                         
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3-7-3 
Justification for Investigation ....................................................................................................................... 35 
3-7-4 
Additional Safety Profile Information ....................................................................................................... 35 
3-7-5 
Standards Conformance Demonstrating Safety .................................................................................... 37 
 
DESCRIPTION OF THE DEVICE ................................................................................................................................... 38 
3-8-1 
Components ......................................................................................................................................................... 38 
3-8-2 
Stimulation Settings/Parameters ............................................................................................................... 39 
3-8-3 
Implant Procedure ............................................................................................................................................ 39 
3-8-4 
Activation of eCoin System ............................................................................................................................. 40 
3-8-5 
Subject Compliance Monitoring ................................................................................................................... 40 
3-8-6 
Safety and Adverse Events ............................................................................................................................. 40 
3-8-7 
Subject Withdrawal & Termination ........................................................................................................... 43 
3-8-8 
Data and Safety Monitoring Board ............................................................................................................ 44 
 
DATA ANALYSIS PLAN ................................................................................................................................................ 45 
3-9-1 
Data Collection ................................................................................................................................................... 45 
3-9-2 
Interim Monitoring ........................................................................................................................................... 45 
3-9-3 
Analysis Plan Summary ................................................................................................................................... 46 
3-9-4 
Primary Hypotheses ......................................................................................................................................... 46 
3-9-5 
Sample Size Calculation .................................................................................................................................. 47 
3-9-6 
Analysis Sets......................................................................................................................................................... 47 
3-9-7 
Exploratory Subgroup Analyses................................................................................................................... 47 
3-9-8 
Calculation of Efficacy Variables ................................................................................................................. 47 
3-9-9 
Missing Outcome Data ..................................................................................................................................... 48 
3-9-10 
Safety Analysis ............................................................................................................................................... 48 
 
DATA HANDLING, RECORD KEEPING AND STUDY MONITORING ........................................................................ 49 
3-10-1 
Confidentiality and Security .................................................................................................................... 49 
3-10-2 
Training ........................................................................................................................................................... 49 
3-10-3 
Documentation, Case Report Forms and Source Documents ...................................................... 49 
3-10-4 
Device Accountability ................................................................................................................................. 50 
3-10-5 
Monitoring Procedures, Auditing, and Inspecting .......................................................................... 50 
3-10-6 
Protocol Deviations and Compliance ................................................................................................... 51 
 
METHODS, FACILITIES, AND CONTROL INFORMATION ......................................................................................... 52 
3-11-1 
Device Manufacturer .................................................................................................................................. 52 
 
STUDY SITES AND INVESTIGATORS ........................................................................................................................... 53 
3-12-1 
Organization and Participating Center .............................................................................................. 53 
3-12-2 
Funding Source and Conflicts of Interest ............................................................................................ 53 
3-12-3 
Institutional Review Board / Ethics Committees ............................................................................ 53 
3-12-4 
Roles and Responsibilities ......................................................................................................................... 54 
3-12-5 
Subject Compensation ................................................................................................................................ 55 
 
STUDY TIMETABLE ...................................................................................................................................................... 55 
4 
ATTACHMENTS .............................................................................................................................................. 56 
 
3-DAY VOIDING DIARY ............................................................................................................................................... 57 
 
MANUALS, AND LABELS ............................................................................................................................................. 58 
 
INVESTIGATOR’S BROCHURE ..................................................................................................................................... 59 
 
PATIENT TRIAL BROCHURE ....................................................................................................................................... 60 
 
INFORMED CONSENT DOCUMENT ............................................................................................................................ 61 
 
PATIENT GLOBAL IMPRESSION OF IMPROVEMENT ................................................................................................ 62 
 
PATIENT IMPLANTATION CARD ................................................................................................................................ 63 
 
CASE REPORT FORMS ................................................................................................................................................. 64 
 
ADVERSE EVENT FORM .............................................................................................................................................. 65 
 
DSMB CHARTER ......................................................................................................................................................... 66 
 
OUS STUDY FOR HYPERTENSION PROTOCOL ......................................................................................................... 67 
 
OUS STUDY FOR HYPERTENSION CRFS FOR INFECTIONS ................................................................................... 68 
 
OUS STUDY FOR HYPERTENSION DSMB LETTER RECOMMENDING SUSPENSION OF IMPLANTATION AT 
SITE 12 69 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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SNS RISK ASSESSMENT (110-1493) .................................................................................................................... 70 
 
SUMMARY OF RISKS AND MITIGATIONS .................................................................................................................. 71 
 
DESIGN VERIFICATION AND VALIDATION REPORTS .............................................................................................. 72 
 
ETHYLENE OXIDE STERILIZATION VALIDATION REPORTS................................................................................... 73 
 
STERILE PACKAGING VALIDATION REPORT............................................................................................................ 74 
 
ENGINEERING DRAWINGS .......................................................................................................................................... 75 
 
ECOIN DEVICE MATERIALS ........................................................................................................................................ 76 
 
TEMPLATE INVESTIGATOR AGREEMENT ................................................................................................................. 77 
 
CLINICAL MONITORING PLAN ................................................................................................................................... 78 
 
ASSEMBLY PROCEDURE ECOIN DEVICE ................................................................................................................... 79 
 
ASSEMBLY PROCEDURE STERILIZATION AND PACKAGING CLINICAL MONITORING PLAN ............................. 80 
 
LIST OF INVESTIGATORS ............................................................................................................................................. 81 
 
303-1122 SOFTWARE DESIGN SPECIFICATION SNS .......................................................................................... 82 
 
BIOCOMPATIBILITY REPORTS ................................................................................................................................... 83 
 
 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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1 Introduction 
 Name, Address, and Signature of Sponsor 
 
Name:     Stacy Chambliss 
 
Title:        Chief of Scientific Review 
            
Address: 
Valencia Technologies Corporation  
28464 Westinghouse Place 
Valencia, CA 91355 
United States 
 
 
Phone: +1 (661) 775-1414 ext. 1002 
 
Fax: +1 (661) 775-1411 
 
Email: schambliss@valenciatechnologies.com 
 
 
Signature of Sponsor:___________________________ Date: ____________ 
 Overview 
Overactive bladder (OAB) is a clinical diagnosis characterized by the presence of 
bothersome urinary symptoms including urgency, frequency, nocturia, and urgency 
incontinence. Urinary incontinence is a prevalent condition that markedly impacts 
quality of life affecting both men and women (1). In population based studies, the 
prevalence of OAB ranges from 7% to 27% in men, and 9% to 43% in women (2-9). 
However, urgency urinary incontinence, characterized by involuntary leakage of urine 
that is associated with a sudden compelling desire to void, is more common in women.  
Because urgency urinary incontinence can be difficult to distinguish from stress urinary 
incontinence, total incontinence episodes are often measured in the clinical trial 
setting. Suffering from unpredictable loss of urine and associated odor or related 
symptoms, the burden on quality of life is well documented.  
While physical therapy and surgery are relatively effective treatments for stress urinary 
incontinence, disorders of the detrusor muscle and/or neural regulation of the lower 
urinary tract system remain quite challenging to treat well. There are a number of 
treatments including first line behavioral therapies and second line medications (anti-
muscarinics or oral β3-adrenoceptor agonists), but many patients remain in poor control.  
For those not well treated by behavioral therapy or medications, or intolerant of 
medications, percutaneous tibial nerve stimulation (PTNS) as well as sacral nerve 
stimulation (SNS) are approved for marketing by the National Institutute for Health and 
Clinical Excellence (NICE) in the United Kingdom and by the Food and Drug 
Administration in the United States. In the US, PTNS is cleared for treatment of 
overactive bladder and the associated symptoms of urinary frequency, urinary urgency 
and urinary urge incontinence.  Furthermore, a category I CPT code was approved by 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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the Centers for Medicare and Medicaid Services (effective Jan. 1, 2011). Percutaneous 
tibial nerve stimulation, described by Stoller in the late 1990s, has been documented in a 
large number of medium sized clinical studies for the treatment of overactive bladder.  
For PTNS, given the need for maintenance therapy over the long-term (10), the expense 
of such maintenance visits, and waning efficacy of the therapy when conducted in the 
home (11), the use of a tiny fully-implantable device is likely to have advantages in 
implementation.  Such advantages may include automated compliance, lower cost over 
device life compared with long term visit costs, and improved efficacy through accurate 
device placement by visualization of tibial nerve compared with percutaneous 
administration at home. 
1. Burgio KL, Locher JL, Goode PS, et al. Behavioral vs drug treatment for 
urge urinary incontinence in older women: a randomized controlled trial. 
Jama 1998;280:1995-2000. 
2. Choo MS, Ku JH, Lee JB et al: Cross-cultural differences for adapting 
overactive bladder symptoms: results of an epidemiologic survey in Korea. 
World J Uro 2007; 25: 505.  
3. Corcos J and Schick E: Prevalence of overactive bladder and incontinence 
in Canada. Can J Urol 2004; 11: 2278.  
4. Coyne KS, Sexton CC, Vats V et al: National community prevalence of 
overactive bladder in the United States stratified by sex and age. Urology 
2011; 77: 1081. 
5. Tikkinen, KA, Auvinen A, Tiitinen A. et al: Reproductive factors associated 
with nocturia and urinary urgency inin women: A population-based study in 
Finland. Am J Obstet Gynecol 2008: 199: 153 e1.  
6. Irwin DE, Milsom I, Hunskaar S et al: Population-based survey of urinary 
incontinence, overactive bladder, and other lower urinary tract symptoms in 
five countries: Results of the EPIC study. Eur Urol 2006; 50: 1306.  
7. Stewart WF, Van Rooyen JB, Cundiff GW et al: Prevalence and burden of 
overactive bladder in the United States. World J Uro 2003; 20: 327.  
8. Herschorn S, Gajewski J, Schulz J, et al: A population-based study of 
urinary symptoms and incontinence: The Canadian Urinary Bladder Survery. 
BJU Int 2008; 101; 52.  
9. Milsom I, Abrams P, Cardozo L et al: How widespread are the symptoms of 
an overactive bladder and how are they managed? A population-based 
prevalence study. BJU Intl 2001; 87: 760. 
10. Yoong, Wai, et al. "Neuromodulative treatment with percutaneous tibial nerve 
stimulation for intractable detrusor instability: outcomes following a shortened 6‐
week protocol." BJU international 106.11 (2010): 1673-1676. 
11. van der Pal F, van Balken MR, Heesakkers JP, et al: Percutaneous tibial 
nerve stimulation in the treatment of refractory overactive bladder syndrome: 
is maintenance treatment necessary? BJU Int 2006, 97(3):547–550. 
 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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2 Report of Prior Investigations  
 Prior Publications of Animal Studies 
The underlying science in support of tibial nerve stimulation for treatment of overactive 
bladder has been well described in published scientific literature.  For example, in 1966, 
McPherson first demonstrated in a cat model that stimulation of the cut ends of dorsal 
spinal roots or various peripheral nerves including the posterior tibial nerve can 
effectively inhibit bladder contractions (12).  The hypothesis for this effect was an action 
of neural circuitry in the forebrain, as intercollicular decerebration or thoracic spinal cord 
transection abolished the effect (13).  Later, in 1980, Sato et al. verified that electrical 
stimulation of afferent nerves to hind limb muscles, but not cutaneous afferents, inhibited 
reflex bladder activity in the anesthetized cat (14).  Three years later, McGuire and 
Morrissey used electrical stimulation of the hindquarter nerves to treat detrusor instability 
in spinal injured nonhuman primates before moving onto demonstrate such effect in the 
clinical setting in 16 patients (15).  Next, case studies were conducted and then a 
number of randomized, controlled trials.  
 
The tibial nerve is a mixed nerve comprised of sensory and motor nerve fibers. It is by 
action of central afferent fibers that neuromodulation of the tibial nerve works to restore 
normal control of an imbalanced voiding reflex.  It is the large diameter somatic afferent 
fibers of the tibial nerve that cause inhibition of bladder activity by way of central 
inhibition of the micturition reflex pathway in the spinal cord or the brain. Such is 
confirmed by studies in anaesthetized female cats (14). Neuromodulation of the tibial 
nerve is presumed to improve or restore normal control of an imbalanced voiding reflex 
by action of the central afferents (12, 17).  Thus, the therapy aims to cause detrusor 
inhibition by acute electrical stimulation of afferent tibial nerve fibers.  Interestingly, it 
appears that the same spinal roots (L4-S3) are targeted by both sacral nerve stimulation 
and tibial nerve stimulation.  It appears that stimulation of the sacral roots, sacral nerve, 
pudendal nerve and tibial nerve all affect central components of the neural circuits 
controlling the bladder, yet we can deduce some distinctions in the action.  That is, a 
study by Tai and colleagues shows that short duration stimulation of the tibial nerve 
causes a persistent post-stimulation inhibition and increase of bladder capacity (18) that 
is replicated by many tibial nerve clinical studies, yet the effects of sacral nerve 
stimulation are shown to go away once stimulation is stopped (19).  
 
As the bladder is controlled by sympathetic, parasympathetic, and somatic nervous 
systems that are regulated by the pontine micturition center (PMC), it is likely that tibial 
nerve stimulation acts on the PMC, either via the pelvic nerve or pudendal nerve or both. 
Bladder contraction (micturition) is controlled via the pelvic nerve (S2-S4) and 
continence is controlled via the hypogastric nerve (T10-L2) and the pudendal nerve (L4-
S3); it is thereby deduced that stimulation of the large somatic afferent fibers of the tibial 
nerve, with spinal roots from L4-S3, finds its effect on the bladder via either the pelvic or 
the pudendal nerve. 
12. McPherson A. The effects of somatic stimuli on the bladder in the cat. J Physiol. 
1966;185(1):185–96.  
13. McPherson A. Vesico-somatic reflexes in the chronic spinal cat. J Physiol. 
1966;185(1):197–204.PubMed 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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Valencia Technologies Corporation          Doc. No. 111-3186 Rev. 1.6                         
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14. Sato A, Sato Y, Schmidt RF, Torigata Y. Somato-vesical reflexes in chronic 
spinal cats. J Auton Nerv Syst. 1983;7:351–62.PubMedCrossRef 
15. McGuire EJ, Zhang SC, Horwinski ER, Lytton B. Treatment of motor and sensory 
detrusor instability by electrical stimulation. J Urol. 1983;129(1):78–9.  
16. van der Pal, F., M. van Balken, and J. Heesakkers. "Maintenance percutaneous 
tibial nerve stimulation (PTNS) treatment in successfully treated patients with 
refractory overactive bladder syndrome: a necessity."Eur Urol 47.Suppl 4 (2005): 
144. 
17. Vandoninck, Vera, et al. "Posterior tibial nerve stimulation in the treatment of 
urge incontinence." Neurourology and urodynamics 22.1 (2003): 17-23. 
18. Tai C, Shen B, Chen M, Wang J, Roppolo JR, de Groat WC. Prolonged 
poststimulation inhibition of bladder activity induced by tibial nerve stimulation in 
cats. Am J Physiol Ren Physiol. 2011;300(2):F385–92. 
doi:10.1152/ajprenal.00526.2010.CrossRef 
19. Herbison GP, Arnold EP. Sacral neuromodulation with implanted devices for 
urinary storage and voiding dysfunction in adults. Cochrane Database Syst Rev. 
2009; Suppl 2:CD004202. doi:10.1002/14651858.CD004202.pub2 
20. Oerlemans, Dennis JAJ, and Philip EV Van Kerrebroeck. "Sacral nerve 
stimulation for neuromodulation of the lower urinary tract." Continence. Springer 
London, 2009. 217-226. 
 Human Studies 
2-2-1 Prior Publications of Tibial Nerve Stimulation for Overactive 
Bladder 
Inhibition of detrusor activity by peripheral neuromodulation of the posterior tibial nerve 
was first described by McGuire et al. (21) and more recent authors such as Govier et al. 
(22), van Balken et al. (23) and Vandoninck et al. (24) have confirmed a 60–80% 
positive response rate after 12 weekly treatments with percutaneous tibial nerve 
stimulation.  According to a meta-analysis by Gaziev et al. (25), level 1 evidence is 
available and supportive of the safety and efficacy of tibial nerve stimulation for 
overactive bladder.  Data available on the safety of percutaneous tibial nerve stimulation 
shows no major concerns for safety.  For example, in the 24 month follow up study to the 
SUmiT trial, the authors find there were no reported treatment related adverse events in 
the 50 subjects through 24 months (26).  Four subjects reported five adverse events with 
unknown causes (UTI, pulling feeling on feet, bladder pressure, pinched nerve and slow 
stream). 
21. McGuire, E. J., et al. "Treatment of motor and sensory detrusor instability by 
electrical stimulation." The Journal of urology 129.1 (1983): 78-79. 
22. Govier, Fred E., et al. "Percutaneous afferent neuromodulation for the refractory 
overactive bladder: results of a multicenter study." The Journal of urology 165.4 
(2001): 1193-1198. 
23. van Balken, Michael R., et al. "Posterior tibial nerve stimulation as 
neuromodulative treatment of lower urinary tract dysfunction." The Journal of 
urology 166.3 (2001): 914-918. 
24. Vandoninck, Vera, et al. "Posterior tibial nerve stimulation in the treatment of 
urge incontinence." Neurourology and urodynamics 22.1 (2003): 17-23. 
25. Gaziev, Gabriele, et al. "Percutaneous tibial nerve stimulation (PTNS) efficacy in 
the treatment of lower urinary tract dysfunctions: a systematic review." BMC 
urology 13.1 (2013): 1. 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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26. Peters, Kenneth M., et al. "Randomized trial of percutaneous tibial nerve 
stimulation versus Sham efficacy in the treatment of overactive bladder 
syndrome: results from the SUmiT trial." The Journal of urology 183.4 (2010): 
1438-1443. 
27. Finazzi-Agrò, Enrico, et al. "Percutaneous tibial nerve stimulation effects on 
detrusor overactivity incontinence are not due to a placebo effect: a randomized, 
double-blind, placebo controlled trial." The Journal of urology184.5 (2010): 2001-
2006. 
28. Amarenco, G., et al. "Urodynamic effect of acute transcutaneous posterior tibial 
nerve stimulation in overactive bladder." The Journal of urology 169.6 (2003): 
2210-2215. 
29. Peters, Kenneth M., et al. "Sustained therapeutic effects of percutaneous tibial 
nerve stimulation: 24‐month results of the STEP study." Neurourology and 
urodynamics 32.1 (2013): 24-29. 
2-2-2 Prior Studies of the Valencia Technologies eCoin System 
The Valencia Technologies eCoin system is currently in the final months of follow-up in a 
prospective, multicenter study to confirm the effectiveness and safety of median nerve 
stimulation using bilateral eCoin devices in resistant or drug intolerant hypertensive 
human subjects. The proposed study for this investigational device exemption addresses 
a different underlying condition from that previously tested with eCoin. Rather, urinary 
urge incontinence treated with tibial nerve stimulation by eCoin is proposed.  Thus, only 
safety data from previous nerve stimulation studies of the eCoin system is presented 
herein. 
2-2-2-1 Safety 
Among the 48 subjects with 96 implanted eCoin devices, there have been no device or 
therapy related Serious Adverse Events. 
Nine subjects have experienced inflammation tenderness or redness at the incision site 
or hand. Four subjects have been treated for an infection at the implant site. One of 
these infections occurred after six months post implant and led to the explant of the 
device. Three out of the four infections were from one clinical center which was 
subsequently shut down at the recommendation of the DSMB. One additional explant of 
a device occurred at this same center due to an unconfirmed infection. All remaining 
Adverse Events were thought to be unrelated to the device or therapy. 
The case report forms for the four reported infections are in Attachment 4-12.  In 
addition, a fifth case report form is included for what the DSMB regarded as an infection 
leading to explant that was not appropriately handled by the center in Ottawa, Canada 
(Site 12). 
The five subject adverse events with infection or explant can be summarized as follows: 
12-005 reported moderate bilateral device infection resolved with antibiotics; 04-008 
reported severe left arm infection treated initially with antibiotics, but ultimately resulting 
in explantation of device from the left arm; 14-006 self-reported mild small infection for a 
few days that resolved on its own; 12-007 reported mild right forearm infection that 
resolved with antibiotics; and 12-004 reported middle finger cellulitis initially treated with 
antibiotics, but ultimately resulting in explantation of device from the right arm.  The 
corresponding adverse event logs, organized according to patient number, are enclosed. 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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The DSMB investigation into the higher than average infection at Site 12 found that the 
Site was not timely in its filing of adverse event reports; and pointed out that the AE on 
12-004 stated that the patient’s swollen middle finger was observed on the very day of 
implantation.  After discussions with site 12 the DSMB was unconvinced that Site 12 had 
put in place an effective plan for confronting its high infection rate.  The DSMB 
recommended suspension of implantation at Site 12 (see attached letter from DSMB – 
Attachment 4-13).  After discussions with the Principal Investigator at Site 12, the 
Company decided to suspend indefinitely any further implantations at Site 12. 
2-2-2-2 Conclusions 
Adverse events related to the eCoin therapy are primarily associated with inflammation 
or infection at the implant site. There have been no device related serious adverse 
events.  

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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 Executive Summary of Non-Clinical Studies 
Preclinical testing of the eCoin subcutaneous neuromodulation system has been 
performed to assure conformance to the design specifications. 
The eCoin subcutaneous neuromodulation system was developed under an ISO 
14971:2012 compliant risk management process to identify potential harms and to 
eliminate risk or reduce risks to an acceptable level. 
2-3-1 Bench Testing - eCoin Device 
The eCoin device is designed to be compliant with all applicable clauses of ISO 14708-
1:2014 Implants for surgery – Active implantable medical devices – Part 1: General 
requirements for safety, marking and for information to be provided by the manufacturer 
and ISO 14708-3:2008 Active implantable medical devices -- Part 3: Implantable 
neurostimulators. 
2-3-1-1 Stimulus Output (207-1093 2.2.1-2.2.5, 2.3.1; 207-1082 2.1-2.5, 2.8)  
The stimulation output pulse amplitude, current regulation (at loads of 300, 600, 1000, 
1500, and 2500 Ohms), pulse width and pulse rate of the eCoin device were verified at 
room temperature, 20 °C, and 45 °C and over battery voltages of 2.7 V, 3 V and 3.2 V. 
Folder: “VOL_018_IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “004_207-1093 SNS Design Verification Test Report.” Refer to 
Sections 2.2.1-2.2.5 and 2.3.1. 
File: “003_207-1082 SNS PCBA Verification Test Report.” Refer to 
Sections 2.1-2.5 and 2.8. 
2-3-1-2 Internal Moisture (207-1093 2.3.2, 2.3.3) 
Residual gas analysis was performed to verify the internal moisture of the hermetically 
sealed eCoin device is no more than 1.5%. This test was repeated on eCoin devices 
after 24 hour water immersion at 80 °C water and a pressure of 2 atm. 
Folder: “VOL_018 IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “004_207-1093 SNS Design Verification Test Report.” Refer to 
Sections 2.3.2 and 2.3.3. 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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CONFIDENTIAL                                               Page 12 of 83 
2-3-1-3 Temperature Exposure (207-1093 2.3.4, 202-1254) 
The eCoin device in a sterile pack passed final functional test after one hour of 
temperature exposure at -10 °C and 55 °C per ISO 14708-3 clause 26.2. In addition as 
part of the packaging validation, eCoin devices passed functional test after exposure to 
climatic conditioning per ASTM D4332-13. 
Folder: “VOL_018 IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “004_207-1093 SNS Design Verification Test Report.” Refer to 
Section 2.3.4.   
Folder: “VOL_020_IDE Attachment 4-18 Sterile Packaging Validation 
Report” 
File: “001_4.18 202-1254 SNS Device Packaging Validation Report” 
2-3-1-4 Pressure Exposure (207-1093 2.3.5)  
The eCoin device passed final functional test after one hour of pressure exposure at 70 
kPa and 150 kPa per ISO 14708-1:2014 clause 25. 
Folder: “VOL_018 IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “004_207-1093 SNS Design Verification Test Report.” Refer to 
Section 2.3.5. 
2-3-1-5 Random Vibration (207-1093 2.3.7)  
The eCoin device passed final functional test after random vibration at 5 Hz to 500 Hz 
for 30 minutes in each of three mutually perpendicular axes per ISO 14708-1:2014 
clause 23.2.  
Folder: “VOL_018 IDE Attachment 4-16 Design Verification and 
Validation Reports”  
File: “004_207-1093 SNS Design Verification Test Report.” Refer to 
section 2.3.7.  
2-3-1-6 Mechanical Shock (207-1093 2.3.8)  
The eCoin device passed final functional test after mechanical shock per ISO 14708-
1:2014 clause 23.7 (1 ms duration 500 g half-sine). 
Folder: “VOL_018 IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “004_207-1093 SNS Design Verification Test Report.” Refer to 
Section 2.3.8. 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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Valencia Technologies Corporation          Doc. No. 111-3186 Rev. 1.6                         
CONFIDENTIAL                                               Page 13 of 83 
2-3-1-7 Mechanical Squeeze Test (207-1093 2.3.9)  
The eCoin device passed final functional test following a ten minute exposure to a force 
of 45 N applied to the top center of the device over an area of 0.5 cm squared. 
Folder: “VOL_018 IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “004_207-1093 SNS Design Verification Test Report.” Refer to 
Section 2.3.9.   
2-3-1-8 Battery UL Testing (EA1821) 
The eCoin device battery passed testing per UL 1642 5th edition including short circuit 
(room temperature and 55 °C), abnormal charging, crush, impact, shock, vibration, 
heating, temperature cycling, low pressure and projectile.   
Folder: “VOL_018_IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “013_EA1821_RPT_Valencia CR1612_UL1642.”  
2-3-1-9 Battery External Short Test (207-1093 2.3.12)  
The eCoin device battery under an external short circuit fault condition was verified to 
generate less than a 2 °C temperature rise at the device surface when implanted 
subcutaneously (ISO 14708-3:2008 clause 17.1). 
Folder: “VOL_018 IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “004_207-1093 SNS Design Verification Test Report.” Refer to 
Section 2.3.12. 
2-3-1-10 Electrocautery Immunity Test (207-1093 2.3.13)  
The eCoin device passed final functional test following a 10 second exposure to a 
conducted 500 kHz since wave delivering 10 V peak to peak between the anode and 
cathode approximating the signal from monopolar electrocautery applied no closer than 
25 cm from the eCoin device. 
Folder: “VOL_018 IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “004_207-1093 SNS Design Verification Test Report.” Refer to 
Section 2.3.13. 
 
 
 
 
 
 
 
 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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Valencia Technologies Corporation          Doc. No. 111-3186 Rev. 1.6                         
CONFIDENTIAL                                               Page 14 of 83 
2-3-1-11 Corrosion Test (207-1093 2.4.1)  
No corrosion of the eCoin case, feed through anode or cathode in phosphate buffered 
physiological saline at 37 °C was observed after continuous stimulation at maximum 
amplitude until battery depletion. 
Folder: “VOL_018 IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “004_207-1093 SNS Design Verification Test Report.” Refer to 
Section 2.4.1. 
2-3-1-12 Battery Service Life and Elective Replacement (207-1082 2.6, 2.7; 
201-1016, 201-1111)  
The eCoin battery discharge current and accelerated battery discharge capacity at 37 °C 
were used to verify a 2 year service life at nominal amplitude after a 12 month shelf life 
and a 1 year elective replacement at the maximum amplitude after a 12 month shelf life. 
Folder: “VOL_018_IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File 1: “003_207-1082 SNS PCBA Verification Test Report.” Refer to 
Sections 2.6 and 2.7. 
File 2: “022_ER 201-1016 Rev 1 - CR1612 Battery” 
File 3: “023_ER 201-1111 Rev 1 – CR1612 Battery Discharge 
Capacity RIR 419-356” 
2-3-1-13 Accelerated Life Test (207-1082 2.9)  
The eCoin electronics assembly (PCBA) passed final functional test following a highly 
accelerated life test (HALT) at 125 °C for 1000 hours while under power with a supply 
voltage of 3.2 volts. 
Folder: “VOL_018_IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “003_207-1082 SNS PCBA Verification Test Report.” Refer to 
Section 2.9. 
2-3-1-14 Temperature Cycling Test (207-1082 2.10)  
The eCoin electronics assembly (PCBA) passed final functional test following 
temperature cycling test per MIL-STD-883H Method 1010, Condition B (10 cycles, -55 
+0/-10 degrees Centigrade to 125 +15/-0 degrees Centigrade, 10 minute dwell time 
minimum). 
Folder: “VOL_018_IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “003_207-1082 SNS PCBA Verification Test Report.” Refer to 
Section 2.10. 

 
Original Application for an Investigational Device Exemption 
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Valencia Technologies Corporation          Doc. No. 111-3186 Rev. 1.6                         
CONFIDENTIAL                                               Page 15 of 83 
2-3-1-15 Laser Seam Weld Validation (202-1436)  
The eCoin device laser seam weld process was validated (IQ, OQ, PQ) to demonstrate 
that it produces a reliable hermetic seam weld. Acceptance criteria included visual 
inspection, fine leak, gross leak and cross section for weld penetration. 
Folder: “VOL_018_IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “001_202-1436 PVR SNS Device Seam Weld Top Cover and 
Feed thru Case.”  
2-3-2 Bench Testing External Controller 
The External Controller is designed to be compliant with all applicable clauses of AAMI / 
ANSI ES60601-1:2005/(R) 2012 and A1:2012, c1:2009/(R) 2012 and a2:2010/(r) 2012 
(consolidated text) Medical Electrical Equipment – Part 1: General requirements for 
basic safety and essential performance, IEC 60601-1-2:2014 Medical electrical 
equipment – Part 1-2: General requirements for basic safety and essential performance 
– Collateral standard: Electromagnetic disturbances - Requirements and tests. 
2-3-2-1 External Controller Output (207-1541 4.2.1- 4.2.8) 
The External Controller was verified to meet all output command and command data 
transmission and timing requirements. 
Folder: “VOL_018_IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “005_207-1541 SNS External Controller Verification Test 
Report.” Refer to Sections 4.2.1 – 4.2.8.  
2-3-2-2 External Controller Battery Discharge and Charge Time (207-1541 
4.2.9, 4.2.10)  
The External Controller was verified to provide at least 7 days of standby operation and 
15 minutes of transmit operation on a single battery charge. The External Controller 
charging with fully discharged battery was verified to complete within 6 hours. 
Folder: “VOL_018_IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “005_207-1541 SNS External Controller Verification Test 
Report.” Refer to Sections 4.2.9 and 4.2.10. 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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Valencia Technologies Corporation          Doc. No. 111-3186 Rev. 1.6                         
CONFIDENTIAL                                               Page 16 of 83 
2-3-2-3 External Controller Battery Safety Testing (RSZBHST 160325326, 
VTC-002A (IEC 60950-1 4.3.8), 207-1541 4.2.11 – 4.2.13, 4.2.15)  
The External Controller rechargeable Li-polymer battery has undergone safety testing 
and passed per IEC62133:2012. In addition, the battery protection circuitry for over-
charging, over-discharge, and over-heating were verified to operate as specified. Battery 
short-circuit protection was verified to operate as specified and also passed testing per 
IEC 60950-1 4.3.8. 
Folder: “VOL_018_IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File 1: “014_005_RSZBHST 160325326.” 
File 2: “021_External Controller Safety Testing VTC_002A IEC 
60601-1 3rd ed Ec01 Remote.” 
File 3: “005_207-1541 SNS External Controller Verification Test 
Report.” Refer to Sections 4.2.11 – 4.2.13 and 4.2.15. 
2-3-2-4 External Controller Over-heat Shutdown (207-1541 4.3.2, 4.3.3)  
The External Controller has been verified to shut-down transmission if the temperature 
of the device exceeds 48 °C. 
Folder: “VOL_018_IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “005_207-1541 SNS External Controller Verification Test 
Report.” Refer to Sections 4.3.2 and 4.3.3.  
2-3-2-5 External Controller IEC 60601-1 (VTC-002A)  
The External Controller has passed applicable clauses of IEC 60601-1: 2005 + CORR. 1 
(2006) + CORR. 2 (2007) + AM1 (2012) or IEC 60601-1: 2012. This includes clauses 5.7 
Humidity, 8.7 Leakage Current, 8.8.3 Dielectric Strength, 8.8.4.1 Enclosure Ball 
Pressure Test, 11.1.1 Excessive Temperatures, 11.6.1 Cleaning, Sterilization 
Disinfection and 15.3 Mechanical Strength (Push, Drop and Mould Stress Relief). 
Folder: “VOL_018_IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “021_External Controller Safety Testing VTC_002A IEC 60601-1 
3rd ed Ec01 Remote” 
File Attachments: “017_External Controller Safety Testing VTC-
002A Attachment A Photographs;” “018_External Controller Safety 
Testing VTC-002A Attachment B Schematics;” “019_External 
Controller Safety Testing VTC-002A Attachment C Calibration;” and 
“020_External Controller Safety Testing VTC-002A Attachment D 
Specifications.”  
2-3-3 MR Compatibility 
The eCoin Subcutaneous Neuromodulation System has not been evaluated for safety 
and compatibility in the MRI environment and is considered MRI unsafe. Patients with 
the eCoin implant should not undergo Magnetic Resonance Imaging (MRI). 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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Valencia Technologies Corporation          Doc. No. 111-3186 Rev. 1.6                         
CONFIDENTIAL                                               Page 17 of 83 
2-3-4 Electrical Safety and Electromagnetic Compatibility 
2-3-4-1 Electromagnetic Non-Ionizing Radiation Immunity (SD72116479-
0516, 207-1093 2.3.6)  
The eCoin device passed final functional test after and remained immune during 
exposure to electromagnetic non-Ionizing radiation per ISO 14708-3 Clause 27. 
Folder: “VOL_018_IDE 4-16 Design Verification and Validation 
Reports” 
File 1: “016_SD72116479-0516-0516 CISPR 11 Class B ESD and 
ISO14708-3 Test Report.” Refer to Section 4.  
File 2: “004_207-1093 SNS Design Verification Test Report.” Refer 
to Section 2.3.6. 
2-3-4-2 Current Leakage (207-1093 2.3.10)  
The direct current leakage between the anode and cathode of the eCoin was verified to 
be less than less than 0.75 microamperes / square millimeter of electrode surface per 
ISO 14708-3 clause 16.2. Notes: For a direct current leakage less than 1 microampere, 
the 4.0 ±0.2mm diameter cathode current density is less than 0.08 microamperes per 
mm-squared. The cathode is worst case since it has a smaller surface area than the 
anode. 
Folder: “VOL_018 IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “004_207-1093 SNS Design Verification Test Report.” Refer to 
Section 2.3.10. 
2-3-4-3 Insulation Leakage (207-1093 2.3.11)  
After preconditioning by total immersion into 9 g/l saline at 37 °C for at least 10 days, the 
eCoin insulation at maximum stimulation amplitude was verified to be greater than 3.3 
kOhm based on no more than a 10% reduction in amplitude when the load is reduced 
from 600 Ohms to 300 Ohms (measured greater than 30 kOhm). 
Folder: “VOL_018 IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “004_207-1093 SNS Design Verification Test Report.” Refer to 
Section 2.3.11. 
2-3-4-4 Electrostatic Discharge (SD72116479-0516) 
The eCoin device passed final functional test and demonstrated safe operation after 
exposure to electrostatic discharge per IEC 61000-4-2 up to + 8 kV direct contact and up 
to + 15 kV air discharge. 
Folder: “VOL_018 IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “016_SD72116479-0516 CISPR 11 Class B ESD and ISO14708-3 
Test Report.” Refer to Section 3.1. 
 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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Valencia Technologies Corporation          Doc. No. 111-3186 Rev. 1.6                         
CONFIDENTIAL                                               Page 18 of 83 
2-3-5 Electrical Safety and EMC External Controller 
2-3-5-1 Electromagnetic Emissions and Non-Ionizing Radiation Immunity 
(SD72110544-1015)  
The External Controller has undergone testing and passed EMC emissions and 
immunity per IEC 60601-1-2:2014. This includes radiated and conducted emissions per 
CISPR 11 Class B, harmonic current emissions per EN61000-3-2 Class A and voltage 
fluctuations and flicker per EN 61000-3-3. Immunity testing includes electrostatic 
discharge per IEC 61000-4-2, amplitude modulated RF EM fields per IEC 61000-4-3, 
proximity RF fields from wireless communication equipment per IEC 61000-4-3, 
electrical fast transients per IEC 61000-4-4, surge per IEC 61000-4-5, RF common 
mode per IEC 61000-4-6, power magnetic field of 30 A/m at 50Hz and 60 Hz per IEC 
61000-4-8 and voltage dip and interruptions per IEC 61000-4-11. 
Folder: “VOL_018 IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “015_SD72110544-1015 External Controller EMC Test Report.” 
Refer to Section 3. 
2-3-6 Software eCoin Device (209-1035, 209-1061, 303-1122)   
The level of safety concern for the eCoin device firmware is Moderate since a failure or 
latent design flaw could directly result in a minor injury to the patient by leading to 
uncomfortable levels of stimulation and/or the need for premature device explant.  
Folder: “VOL_018 IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File 1: “006_209-1035 SNS Firmware Verification Test Report” 
File 2: “007_209-1061 Firmware Unit Test Report” (plus 008_209-
1061 Appendix A & 009_209-1061 Appendix B) 
File 3: “024_209-3264 Rev 1 - SNS Firmware Verification Test Report 
OAB”  
Folder: “VOL_028_IDE Attachment 4-26 303-1122 Software Design 
Specification SNS” 
File: “001_4.26 303-1122 Software Design Specification SNS.”  
2-3-7 Software External Controller (207-1541, 303-1122)  
The level of safety concern for the External Controller firmware is Minor since its function 
is limited such that a failure or design flaw is unlikely to cause any injury to the patient or 
operator. Verification and validation testing has been completed with all software design 
requirements met.  
Folder: “VOL_018 IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “005_207-1541 SNS External Controller Verification Test 
Report.” 
Folder: “VOL_028_IDE Attachment 4-26 303-1122 Software Design 
Specification SNS” 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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Valencia Technologies Corporation          Doc. No. 111-3186 Rev. 1.6                         
CONFIDENTIAL                                               Page 19 of 83 
File: “001_4.26 303-1122 Software Design Specification SNS.” 
2-3-8 Biocompatibility 
2-3-8-1 Cytotoxicity ISO 10993-5 (PBL 14E0355G-M01G) 
Based on the qualitative evaluation of cells exposed to eCoin test article extract, the 
eCoin test article was not considered to have a cytotoxic effect (no reactivity). 
Folder: “VOL_029 IDE Attachment 4-27 Biocompatibility Reports” 
File: “001_Cytotoxicity Pacific BioLabs Study No. 14E0355G-M01G.” 
2-3-8-2 Sensitization ISO 10993-10 (PBL 14H0049G-X01G)  
Under the conditions of the study, the eCoin test article did not elicit sensitization 
reactions. 
Folder: “VOL_029_IDE Attachment 4-27 Biocompatibility Reports” 
File: “002_Report Sensitization Pacific BioLabs Study No 
14H0049G-X01G.” 
2-3-8-3 Irritation ISO 10993-10 (PBL 14H0048G-X01G)  
Based on erythema and edema scores, no irritation was noted with the eCoin test article 
when compared to control. Under the conditions of the study, the eCoin test article met 
the requirements for the Intracutaneous (Intradermal) Reactivity Test. 
Folder: “VOL_029_IDE Attachment 4-27 Biocompatibility Reports” 
File: “003_Irritation Pacific BioLabs Study No 14H0048G-X01G.”  
2-3-8-4 Acute Systemic Toxicity ISO 10993-11 (PBL 14H0051G-X01G)   
None of the animals treated with eCoin test article extract exhibited a greater biological 
activity when compared to those treated with the control. Under the conditions of the 
study, the eCoin test article met the requirements of ISO 10993-11. 
Folder: “VOL_029_IDE Attachment 4-27 Biocompatibility Reports” 
File: “004_Acute Systemic Toxicity Pacific BioLabs Study No 
14H0051G-X01G.”  

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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Valencia Technologies Corporation          Doc. No. 111-3186 Rev. 1.6                         
CONFIDENTIAL                                               Page 20 of 83 
2-3-8-5 Sub-Chronic Systemic Toxicity 90 Day ISO 10993-6 (PBL 16C0069G-
X01G)  
The results suggest that the device, when implanted subcutaneously was well-tolerated 
in male and female Sprague Dawley rats over a period of 94 days. There was no 
evidence of test article effect on body weights and body weight changes. Changes in 
several hematology and clinical chemistry parameters that reached statistical 
significance were not considered test article related because they appeared to be 
sporadic and values were within the normal range typical for this animal species. There 
were no statistically significant differences in coagulation factors. 
There were no microscopic observations in the systemic tissues or organs of male and 
female rats that were considered to be related to the subcutaneous implantation of the 
test article. There were two notable lesions that were identified macroscopically in two 
female rats from the test group; a lump present near the implant site (Animal #13) and 
right eye opacity (Animal # 12). The lesion near the implant site observed in one female 
animal was identified as M-adenocarcinoma of mammary gland and was considered 
incidental. The ocular changes observed in Animal #12 were considered to be of a 
traumatic etiology. The local, subcutaneous tissue response to both the control article 
and test article was comparable for male and female rats as characterized primarily by 
fibrosis, neovascularization, and cellular infiltrates.     
Folder: “VOL_029 IDE Attachment 4-27 Biocompatibility Reports” 
File: “005_Sub-chronic Toxicity Pacific BioLabs Study No. 
16C0069G-X01G.”  
2-3-8-6 Genotoxicity ISO 10993-3 (PBL 14E0349G-X01G, 16E0213G-X01G)  
Based on the criteria and conditions the Bacterial Mutagenicity Test (Ames Assay) used, 
the eCoin test article was considered non-mutagenic. In a ISO 10993-3:2014 compliant 
mouse lymphoma assay, the mutant frequencies and cloning efficiencies of preparations 
treated with the eCoin test article were within limits defined for a negative response. 
Accordingly, the eCoin is considered to be non-mutagenic and non-clastogenic in the 
mouse lymphoma assay test system. 
Folder: “VOL_029 IDE Attachment 4-27 Biocompatibility Reports” 
File 1: “006_Genotoxicity AMES PBL No 14E0349G-X01G.” 
File 2: “007_Genotoxicity Mouse Lymphoma 16E0213G-X01G.”  
2-3-8-7 Implantation 90 Day ISO 10993-6 (PBL 14E0356G-X01G)  
Under the conditions of the study, the eCoin test article was considered a non-irritant to 
the tissue as compared to the negative control article. 
Folder: “VOL_029 IDE Attachment 4-27 Biocompatibility Reports” 
File: “008_Implantation Pacific BioLabs Study No. 14E0356G-X01G.” 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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Valencia Technologies Corporation          Doc. No. 111-3186 Rev. 1.6                         
CONFIDENTIAL                                               Page 21 of 83 
2-3-8-8 Pyrogen - Material Mediated ISO 10993-11 (PBL 16C0182G-X01G)  
The test was performed according to ISO 10993-11 and USP <151> guidelines. All 
animals appeared healthy during the test and none of the tested rabbits exhibited 
individual increase in temperature greater or equal to 0.5°C when compared to the 
control temperature. Based on criteria for this test, the test article meets USP <151> 
requirements for the absence of pyrogens 
Folder: “VOL_029_IDE Attachment 4-27 Biocompatibility Reports” 
File: “009_Material-Mediated Pyrogenicity 16C0182G-X01G.” 
2-3-8-9 Ethylene Oxide Sterilization Residuals ISO 10993-7 (Nelson 749416)  
The ethylene oxide residual for the eCoin device was less than 0.012 mg (1.2 
micrograms per centimeter squared of device surface area). The ethylene chlorohydrin 
residual for the eCoin device was less than 0.038 mg (3.8 micrograms per centimeter 
squared of device surface area). Both of these are within the ISO 10993-7 limit for 
permanent implants and the tolerable contact limit. 
Folder: “VOL_029_IDE Attachment 4-27 Biocompatibility Reports” 
File: “010_EO Residuals 749416 8XL.” 
2-3-9 Particulate (Nelson Lab Number 884283-01)  
The eCoin device particulate counts meet requirements per ISO 14708-1:2014 clause 
14.2. 
Folder: “VOL_018_IDE Attachment 4-16 Design Verification and 
Validation Reports” 
File: “010_884283-S01 Particulate Test.”  
2-3-10 Sterility (2002-1206)  
The eCoin device ethylene oxide sterilization process was validated per ISO 11135 
using half cycle batch release approach using the over kill method (ISO 11135-
1:2007(E) Annex B). 
Folder: “VOL_019_IDE Attachment 4-17 Ethylene Oxide Sterilization 
Validation Reports” 
File: “001_Ethylene Oxide Sterilization Validation Reports”  
2-3-11 Packaging (202-1254; Westpak 225-15-0053A)  
Validation of the eCoin device packaging demonstrated that the integrity of the final 
package is maintained under the severities of distribution, storage and handling. After 3x 
(worst case) sterilization, baseline samples were tested for seal strength per ASTM 
F88M:2009 and seal integrity per ASTM F1886-09. Remaining samples underwent 
climatic conditioning followed by shipping and handling testing per ASTM D4169-14. 
Zero-aged samples were then tested for seal strength per ASTM F88M:2009 and seal 
integrity per ASTM F1886-09. Remaining samples underwent accelerated and real time 
shelf-life aging (see 2-3-12). 
Folder: “VOL_020_IDE Attachment 4-18 Sterile Packaging Validation 
Report” 
File 1: “001_202-1254 SNS Device Packaging Validation Report.”  
File 2: “003_Appendix B Test Lab Report No 225-15-0053A”  

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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Valencia Technologies Corporation          Doc. No. 111-3186 Rev. 1.6                         
CONFIDENTIAL                                               Page 22 of 83 
2-3-12 Shelf Life (202-1254; Westpak 225-15-0053B, 225-15-0053C) 
Accelerated and real time aging of the eCoin device and its packaging demonstrated 
that the integrity of the final package and device functionality is maintained over the 1 
year device shelf-life. Accelerated aging equivalent to a 13 month shelf life was 
completed per ASTM F1980-07. Real-time aging for 13 months was completed at 
ambient conditions (approximately 25 °C and 50% relative humidity). After aging, 
packaging samples were then tested for seal strength per ASTM F88M:2009 and seal 
integrity per ASTM F1886-09 and the eCoin device underwent final functional testing. 
Folder: “VOL_020_IDE Attachment 4-18 Sterile Packaging Validation 
Report” 
File 1: “001_202-1254 SNS Device Packaging Validation Report” 
File 2: “004_Appendix C Test Lab Report No 225-15-0053B.”  
File 3: “005_Appendix C Test Lab Report No 225-15-0053C 13 Month 
Real Time Aging of the SNS.” 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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Valencia Technologies Corporation          Doc. No. 111-3186 Rev. 1.6                         
CONFIDENTIAL                                               Page 23 of 83 
3 Investigational Plan  
 Purpose 
The investigation is a feasibility study of the safety and efficacy of the Valencia 
Technologies eCoin system in the treatment of urgency urinary incontinence in patients 
with refractory overactive bladder. The study will be completed in 16 months. 
The primary aims are to evaluate the change in urgency incontinence episodes in 
patients after 3 months of tibial nerve stimulation therapy with eCoin and the safety of 
eCoin during the same period. 
 Summary 
This trial is a single arm, prospective study of the safety and effectiveness of eCoin tibial 
nerve stimulation in subjects with refractory overactive bladder as defined by the 
American Urological Association (30). The eCoin neuromodulation device will be 
implanted subcutaneously in the right or left leg of patients with urgency urinary 
incontinence.  After a 4 week implant healing period, subjects will have their devices 
activated (turned ON). After 3 months of device therapy (occurring 4 months post-
implant), the primary endpoint will be assessed.  It is anticipated that subjects will reach 
the full therapeutic effect at approximately 3 months of therapy.  Subjects will be 
followed for an additional 9 months to assess the safety of maintenance stimulation 
therapy with fewer sessions occurring during this time interval. 
30. American Urological Association, OVERACTIVE BLADDER DIAGNOSIS AND 
TREATMENT OF OVERACTIVE BLADDER IN ADULTS AUASUFU Guideline 
(2012); Amended (2014). 
 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urinary Urge Incontinence 
 
 
 
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Valencia Technologies Corporation          Doc. No. 111-3186 Rev. 1.6                         
CONFIDENTIAL                                               Page 24 of 83 
 Protocol  
3-3-1 Study Design 
The study is a single arm, prospective study of the safety and effectiveness of the 
Valencia Technologies eCoin System to stimulate the tibial nerve for the treatment of 
patients with refractory urgency urinary incontinence. 
3-3-2 Subject Selection  
3-3-2-1 Patient Population 
The primary sample size target is 50 subjects with refractory urgency urinary 
incontinence. For enrollment, eligible subjects will be consented and entered into a 
baseline evaluation period to confirm study eligibility with a baseline assessment 
including complete medical history, physical examination, and completion of a 3-day 
voiding diary to quantify voiding behavior, symptoms, and incontinence. Subjects with 
presence of clinically significant bladder outlet obstruction, positive urine cytology, 
positive urine culture, and documented neurogenic bladder dysfunction will be excluded.  
Only subjects who meet all the inclusion and exclusion criteria, and have provided 
informed consent, will be enrolled. It is estimated that approximately 100 subjects will be 
enrolled into baseline evaluation in order to yield 50 implanted subjects (where up to 35 
subjects in the United States will be implanted). 
All eligible enrolled subjects are implanted with the eCoin system after baseline 
assessment.  The implantation side will be left to the discretion of the investigator. 
Approximately 4 weeks post implantation, subjects will return for implant activation at 
which time the device will be activated and therapy will begin. A programming technician 
will implement the activation procedure, setting amplitude of stimulation according to the 
upper level of a subject’s comfort.  
3-3-2-2 Selection Criteria 
Participants shall be screened in accordance with the following inclusion and exclusion 
criteria.  
 Inclusion Criteria 
1. Women and men 18 years and older. 
2. Diagnosis of overactive bladder with urgency urinary incontinence or mixed 
urge and stress incontinence with a predominant urgency component, for at 
least 6 months (self-reported).  
3. Individual has at least one urgency incontinence episode, on average over a 
one-day period, as determined over a 3-day period.  
4. Individual is unresponsive to, inadequately responsive to, or intolerant of 
behavioral, rehabilitation, and pharmacologic therapy.  
5. Individual is able to give his or her written, informed consent. 
6. Individual is mentally competent and able to understand all study requirements. 
7. Individual is willing and able to complete a 3-day voiding diary and quality of life 
questionnaire. 
8. Individual is without pharmacological treatment of overactive bladder 
(antimuscarinics and beta-3 agonists) for 2 weeks prior to baseline. 

 
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 Exclusion Criteria  
1. 
Individual has predominantly stress urinary incontinence. 
2. 
Individual has clinically significant bladder outlet obstruction. 
3. 
Individual has clinically significant pelvic organ prolapse. 
4. 
Individual has abnormal post void residual (i.e., greater than 150 cc). 
5. 
Individual has clinically significant urethral stricture disease or bladder neck 
contracture. 
6. 
Individual has an active urinary tract infection at time of enrollment. 
7. 
Individual has recurrent urinary tract infections defined as 4 or more UTI’s per 
year.  
8. 
Individual has peripheral arterial disease. 
9. 
Individual has chronic venous insufficiency with a history of skin change 
(hyperpigmentation, lipodermatosclerosis, ulceration) in the ankle region. 
10. Individual has morbid obesity. 
11. Individual has had positive urine cytology or diagnosis of bladder or prostate 
cancer. 
12. Individual has neurogenic bladder dysfunction. 
13. Individual is taking an alpha-blocker for benign prostatic hyperplasia. 
14. Individual is pregnant or intends to become pregnant during the study. 
15. Patient is breast feeding or is less than 9-month post-partum.  
16. Individual has the presence of urinary fistula, bladder stone, or interstitial cystitis. 
17. Individual has uncontrolled diabetes mellitus. 
18. Individual has an implanted device. 
19. Individual has been previously treated with sacral nerve stimulation.  
20. Individual has been treated with onabotulinumtoxinA in the previous 9 months 
prior to enrollment. 
21. Individual has been treated with percutaneous tibial nerve stimulation within the 
previous 12 weeks prior to enrollment.  
22. Individual is aware that he or she will need an MRI scan during the study period. 
23. Individual has a clotting or bleeding disorder; antiplatelet and anticoagulant 
therapy may be continued or held at the discretion of the investigator.  
24. Individual has a clinically significant peripheral neuropathy.  
25. Individual is neutropenic or immunocompromised. 
26. Individual has had previous surgery and/or significant scarring at the implant 
location. 
27. Individual has ongoing dermatologic condition at the implant site, including but 
not limited to dermatitis and autoimmune disorders. 
3-3-3 Ethical Considerations  
No critical ethical issues have been identified.  Subjects who are refractory to available 
drug therapy have the potential to gain a new treatment modality through participation in 
the study and to assess the impact of this treatment modality on their incontinence with 
minimal risk.  However, the following are considerations: 

 
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 
Some subjects may not receive clinical benefit from eCoin therapy, but are to 
continue with follow-ups until study completion.  Note that in some cases, benefit 
may be identified over time based on late response and cumulative effects of 
treatment. 
 
Subjects are intended to be without pharmacological medications for overactive 
bladder.  If the addition of medications is medically necessary as described 
herein, such changes may affect a subject’s continued participation in the study. 
 Study Procedures 
All subjects will be followed for 6 months post-activation: collecting a 3-day voiding diary 
reporting the number of incontinence episodes, number of micturitions, voided volumes, 
and quality of life scores at 1, 2, 3, 4 and 6 months post-activation.  
All subjects are expected to remain free of pharmacological medications for overactive 
bladder, unless medically necessary, until the primary endpoint measured at 3 months 
post-activation. Subjects who are taking pharmacologic medication should be washed off 
OAB medications for a period of 2 weeks prior to baseline. 
After the 3 month post-activation study endpoint has been reached, all subjects will be 
monitored at 12 months post-activation.  
At 12 months, the study is concluded.  
3-4-1 Subject Recruitment Plans 
Investigators will identify patients currently under their direct care, and contact patients 
that appear to qualify from medical records.   Investigators will also seek referrals from 
other urology, urogynecology, and gynecology practices.  A member of the site’s clinical 
research team shall assess whether the individual seems suitable for the study.  The 
patient should have a medical history of overactive bladder with urgency incontinence.   
Patients with urgency incontinence who appear to meet the inclusion/exclusion criteria 
from medical records will be contacted by the Investigator or designated study staff and 
presented with the opportunity to participate in the study, including: 
 
 
reason for being identified (refractory urgency urinary incontinence) 
 
therapy description 
 
potential benefits 
 
risks 
 
compensation (see 3-12-5)  
 
If the patient is interested thereafter, they will be brought into the research clinic for 
further screening and informed consent.   
 

 
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3-4-2 Visit Overview 
The ordered enrollment process consists of screening including obtaining written 
consent, completing the baseline evaluation, implantation of eCoin system, and 
establishing the stimulation paradigm for the patient. A flowchart depicting the process is 
provided in Figure 1.  The timing of visits 1 through 4 is described in relationship to the 
immediately previous visit, while the timing of visits 6 through 10 is described in 
relationship to visit 5 (the activation).  
 
For visits involving a 3-day diary, the diary should be completed over 3 consecutive days 
during the 7 days prior to each indicated visit.  The site should give patients a call to 
remind them of the diary requirement at least 3 days prior to each follow up visit.   
 
Visit 1: Screening Procedures (informed consent, urinalysis, PVR, history and 
physical examination, subjects begin 2 week wash-off of OAB medications if 
applicable, concomitant medication therapy review, eligibility determination) 
 
Visit 2: Baseline Assessments (3-day voiding diary, I-QoL, subject sent home 
with 7-day TENS trial instructions) (Time: Between 0 and 28 days from Visit 1) 
 
Visit 3: Implant Procedure (Time: Between 0 and 14 days from Visit 2)  
 
Visit 4: Incision Healing Check (week 2) (Time: Between 9 and 19 days from Visit 
3) 
 
Visit 5: Activation (week 4) (Time: Between 23 and 33 days from Visit 3) 
 
Visit 6 (1 month post-activation): Follow up Assessments (3-day voiding diary, 
adverse event assessment, concomitant medication therapy review, patient 
surveys including I-QoL, patient satisfaction, and patient global assessment of 
improvement) (Time: Between 23 and 33 days from Visit 5) 
 
Visit 7 (2 months post-activation): Follow up Assessments (3-day voiding diary, 
adverse event assessment, concomitant medication therapy review, patient 
surveys including I-QoL, patient satisfaction, and patient global assessment of 
improvement) (Time: Between 51 and 61 days from Visit 5) 
 
Visit 8 (3 months post-activation): Follow up Assessments (3-day voiding diary, 
adverse event assessment, concomitant medication therapy review, patient 
surveys including I-QoL, patient satisfaction, and patient global assessment of 
improvement) (Time: Between 79 and 89 days from Visit 5) 
 
Visit 9 (4 months post-activation): Follow up Assessments (3-day voiding diary, 
adverse event assessment, concomitant medication therapy review, patient 
surveys including I-QoL, patient satisfaction, and patient global assessment of 
improvement) (Time: Between 107 and 117 days from Visit 5) 
 
Visit 10 (6 months post-activation): Follow up Assessments (3-day voiding diary, 
adverse event assessment, concomitant medication therapy review, patient 
surveys including I-QoL, patient satisfaction, and patient global assessment of 
improvement) (Time: Between 163 and 173 days from Visit 5) 
 
Visit 11 (12 months post-activation): Follow up Assessments (3-day voiding diary, 
adverse event assessment, concomitant medication therapy review, patient 
surveys including I-QoL, patient satisfaction, and patient global assessment of 
improvement) (Time: Between 331 and 341 days from Visit 5) 
 
Visit 12 (12 months post-activation): Explantation to follow Visit 11 (Time: On or 
within 30 days of Visit 11) 
 
Visit 13 Incision Healing check (2 weeks post-explantation): visit to assess 
wound healing. (Time: Between 9 and 19 days post-explantation). 
 

 
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Screening 
Baseline 
Implantation 
Incision Healing Check 
Activation  (Follow up Clock Starts) 
1 Month Follow-up 
2 Month Follow-Up 
3 Month Follow-Up: Primary Endpoint 
4 Month Follow-Up 
6 Month Follow-up 
12 Month Monitoring 
Incision Healing Check 
Demographics, screening exam, 
physical exam, & medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
Eligibility Determination 
X X 
 
 
 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
 
3-day Voiding Diary Reminder 
Call 
X X X 
 
 
 
X X X X X 
 
3-day Voiding Diary 
X X X 
 
 
 
X X X X X 
 
Post Void Residual (PVR) 
X 
 
 
 
 
 
 
 
 
 
 
 
Urinalysis 
 
X 
 
 
 
 
 
 
 
 
 
 
I-QoL Assessment 
 
X 
 
 
 
 
X X X X X 
 
7-day TENS Trial Data Collection 
 
 
X 
 
 
 
 
 
 
 
 
 
Patient Reported Satisfaction 
Assessment 
 
 
 
 
 
 
X X X X X 
 
Patient Global Impression of 
Improvement 
 
 
 
 
 
 
X X X X X 
 
Implant or Explant Procedure  
 
 
X 
 
 
 
 
 
 
 
X 
 
Incision Assessment  
 
 
 
X 
 
 
 
 
 
 
 
X 
Activation 
 
 
 
 
X 
 
 
 
 
 
 
 
Completion of Primary Endpoints 
 
 
 
 
 
 
 
X 
 
 
 
 
Completion of Study 
 
 
 
 
 
 
 
 
 
 
 
X 
Subject Assessment for AEs 
 
 
X X X X X X X X X X 
 

 
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Figure 3-1: Summary of Study Process 
3-4-3 Screening for Eligibility Procedures 
Interested adults who are known or present at the research site with refractory urgency 
urinary incontinence may be initially screened for inclusion in the study. Patients’ 
medical records will be reviewed for inclusion/exclusion criteria.  
Patients who initially qualify will be scheduled for a screening visit to assess general 
health and overactive bladder condition.  Urinalysis will be utilized after providing their 
informed consent.  Patients will also be questioned for inclusion/exclusion criteria in 
addition to medical record review.  A history will be taken, physical exam will be 
performed, and general health to participate in the study will be further evaluated by the 
Investigator at the screening visit.  
3-4-4 Prior and Concomitant Therapy  
The intent of the study is to enroll subjects who are refractory to other modes of therapy, 
including behavioral therapy, pelvic floor exercises, and pharmacologic therapy.  
Subjects who are taking pharmacologic agents for overactive bladder or other agents 
that may influence urination at enrollment will be expected to discontinue those 
medications at least 2 weeks prior to baseline.  Subjects who are not taking such agents 
will be expected to remain agent-free until the primary endpoint, A complete list of 
prescription drugs, over-the-counter drugs, or dietary supplements should be taken at 
screening to ensure stability of medications that can affect urination.  
3-4-5 Informed Consent Procedures 
The study as contained in the Informed Consent (see Attachment 4-5) will be presented 
to the individual for consideration at the screening visit. The individual will be given 
adequate time to have all questions answered and to carefully consider participation. If, 
after understanding the purpose, potential risks, potential benefits, and requirements of 
the study, as well as his or her rights as a research participant, the individual agrees to 
participate as evidenced by providing written informed consent, the subject will be 
enrolled to enter the baseline period.  The subject should be allowed to take informed 
consent documents home for further consideration, if needed, and scheduled with an 
additional visit to complete the screening visit.  Informed Consent shall be included in the 
patient’s medical record file and noted in the screening CRF.  
3-4-6 Baseline Visit Assessments 
At the conclusion of the Screening Visit, eligible subjects who have provided informed 
consent will be asked to come back for baseline assessments. 
Baseline assessments will include: 
1) 3-day voiding diary; 
2) I-QoL assessment; 
3) TENS trial instructions; 
Study staff will schedule subject’s implantation procedure to follow baseline 
assessments.  
 
 

 
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3-4-7 TENS Trial 
At baseline, subjects will be sent home with a TENS (transcutaneous electrical nerve 
stimulation) unit and instructions to perform TENS of the tibial nerve twice daily for seven 
days.  The electrical paradigm will be preset to match the electrical paradigm of eCoin 
(pulse width of 0.2 ms and frequency of 20 Hz), but the subject will set the amplitude of 
stimulation to the upper level of comfort.  Subjects should perform one thirty minute 
session in the morning and one in the evening for 7 days (total of 14 sessions).  Subjects 
will also be asked to complete a voiding diary in the last three days of the TENS trial.  
This TENS trial will occur after the baseline visit but before the implantation visit.  The 
purpose of this trial is to ascertain whether there is a relationship between responders to 
TENS and responders to eCoin therapy.  Patients will not be excluded from participation 
in this study based on response to TENS.  This procedure is optional in New Zealand.  
3-4-8 Implantation of Subcutaneous Neuromodulation System  
An implant procedure is to be completed following, but no later than 30 days from, the 
baseline visit.  The eCoin system will be implanted in accordance with the procedures 
outlined in the Surgical Implant Manual set forth in Attachment 0.  The implant procedure 
is conducted as an outpatient procedure under local anesthesia for subcutaneous 
placement. An incision site healing check will be performed 2 weeks post implant. 
Subjects will be provided a minimum of 4 weeks for healing prior to activation of the 
system. 
Prior to discharge from the procedure, the research staff shall review study requirements 
with the subject to help ensure compliance with the follow-up schedule.  All patients will 
be required to return to clinic for an incision assessment visit, one activation visit, one 
safety assessment visit, three follow up visits, followed by one long-term maintenance 
visit as outlined in the protocol. Telephone numbers will be obtained from the participant 
at the time of informed consent to ensure the clinic has the ability to contact the subject 
and primary physician as needed.  Patients will be instructed on post-procedural care 
and activities, and antibiotics and pain medication will be prescribed at the discretion of 
the investigator. 
3-4-9 eCoin Activation 
Four weeks after implantation, subjects will return for device activation.  All subjects will 
have their device activated. 
The subject will be provided with a 3-day voiding diary to complete in the 7 days prior to 
the next visits (occurring 1, 2, 3, 4, 6, and 12 months post-activation). Subjects will be 
reminded by phone by a member of the study staff at least 3 days prior to the next visit 
that they should begin the 3-day diary. Instructions will be given regarding wound care. 
 
3-4-10 Establishment of the Electrical Regimen 
The programming technician will follow programming procedures setting the amplitude 
according to the subject’s upper level of comfort. Subjects will be informed that they may 
periodically feel a tingling or notice a muscle twitch; but if they do, it would be transient 
and they should not feel anything most of the time, if at all.  In particular, subjects may 
feel a motor response (flexing of the big toe and/or fanning of the other toes) and 
sensory response (a radiating sensation is felt at the sole of the foot and in the toes).  
 

 
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3-4-11 Post Activation Follow-up Procedure 
Subjects will be followed up in visits at 1, 2, 3, 4, and 6 months post activation, with the 
primary analysis at 3 months. 
1) Overactive bladder medications and doses should not be given through the 3 
month primary endpoint (unless medication is medically necessary according to 
the “Escape Treatment” guidelines below). 
2) At least 3 days prior to each appointment, the subject will be responsible to 
complete a 3-day voiding diary to be brought with them to each appointment. 
3) Assessments at these follow-up visits are described in the Visit Overview Section 
3-4-2. 
At the follow-up visit 3 months post-activation, the study endpoint will have been 
reached. At this time, the addition of medication is allowed if clinically necessary to 
achieve improved control of overactive bladder symptoms.  
3-4-12 Escape Procedure 
Overactive bladder medications are not allowed until the study endpoints are reached at 
3 months post activation, unless judged medically necessary.  Agents added or 
withdrawn are at the discretion of the Investigator and managing physician(s). Any such 
adjustments are to be noted on the CRF for the next Follow Up visit.  
 Study Endpoints 
3-5-1 Primary Outcome Measures 
3-5-1-1 Primary Effective Outcome Measure 
The change in number of incontinence episodes from baseline to three months post-
activation.  
3-5-1-2 Primary Safety Outcome Measures 
Incidence of System and Procedure Related Adverse Events from implantation to one 
month post-implantation. 
Incidence of all Serious Adverse Events from baseline to 3 months post-activation.  
3-5-2 Key Secondary Outcome Measure 
The percentage of responders in subjects implanted with the device.  Responders are 
defined as subjects with a 50% or greater reduction in urge incontinence episodes from 
baseline to three months post-activation.   
3-5-3 Exploratory Secondary Outcome Measures 
The difference in change from baseline in number of incontinence episodes at three and 
four months post-activation in all responder subjects with data available at three and four 
month visits.   
The change, expressed as a percentage from baseline, in incontinence episodes from 
baseline to three months post-activation in responder subjects.  
The change in number of micturitions from baseline to three months post-activation in 
responder subjects.   

 
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The change in mean voided volume from baseline to three months post-activation in 
responder subjects.   
The change in I-QoL score from baseline to three months post-activation in responder 
subjects.   
The mean change in patient satisfaction score from baseline to 3 months post-activation. 
The mean change in patient global impression of improvement score from baseline to 3 
months post-activation. 
The mean change in quality of life as measured by the IQoL score from baseline to 3 
months post-activation. 
The proportion of subjects who had a 100% reduction (dryness) in the # of incontinent 
episodes/24 hours at 3 months post-activation.  
 Rationale for the Selection of Outcome Measures and Study 
Design 
It is anticipated that eCoin therapy will positively affect a number of symptoms of 
overactive bladder including number of urge incontinence episodes, voiding volume, 
frequency, and nocturia.  Urinary incontinence is associated with substantial routine care 
costs and a clinically significant decrement in health-related quality of life that is similar 
to the impact of other chronic medical conditions like osteoarthritis, chronic obstructive 
pulmonary disease, and stroke (31).  Percutaneous tibial nerve stimulation achieves a 
50-70% response rate.  Thus, it is anticipated that not all subjects will respond to eCoin 
therapy, but that a high level of response in responders would translate to a meaningful 
contribution to overactive bladder care.  Thus, the primary outcome focuses on a 
relatively objective and significant symptom of overactive bladder, the number of 
incontinence episodes in a 3-day period in responder subjects. Of the secondary 
outcomes, quality of life is an important measure of the overactive bladder condition 
because overactive bladder is a symptom-based diagnosis.  The degree of bother 
caused by symptoms directly affects care seeking, treatment intensity, and satisfaction 
with treatment.  However, there has been a historical lack of standardization of such 
patient reported questionnaires on the quality of life of incontinence patients.  Thus, 
Valencia selected two questionnaires based on evidence that each, the I-QOL and the 
ICIQ-UI, proved to be valid and reproducible as a self-administered measure for 
assessing quality of life in patients with urinary incontinence (32, 33).   
 
Given the expected therapeutic equivalence of percutaneous nerve stimulation of the 
tibial nerve to eCoin stimulation of the tibial nerve, it is not expected that the therapy will 
cause adverse events.  Furthermore, prior experience with eCoin implantation in the 
forearm for the treatment of hypertension, shows that the primary concern was infection 
or symptoms of infection, which tend to appear by 30 days post-implantation.  Thus, the 
safety outcomes focus on related events 30 days post-implantation and all serious 
adverse events through the primary endpoint. In addition, safety will be assessed for an 
additional 9 months following the primary endpoint assessment.  
While an important benefit to the eCoin system is that therapy delivery does not require 
the patient to operate a percutaneous device and locate the tibial nerve on a regular 
basis, it is also important to understand how well patients tolerate the device. In order to 
assess patient acceptance, a patient satisfaction grade will be documented for each 
subject at 3 months post activation. 

 
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31. Schultz SE, Kopec JA. Impact of chronic conditions. Health Rep. 2003;14:41–53. 
32. Wagner, T. H., et al. "Quality of life of persons with urinary incontinence: 
development of a new measure." Urology 47.1 (1996): 67-71. 
33. Hajebrahimi, Sakineh, et al. "Validity and reliability of the International 
Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form 
and its correlation with urodynamic findings." Urology journal 9.4 (2012): 685. 
 
 Risk Analysis 
3-7-1 Overview 
The eCoin system risk assessment (Attachment 4-14) has been completed per FDA-
recognized Consensus Standard 5-40: ISO 14971. The risk analysis method identifies 
each potential hazard which could result in patient harm, with action taken to reduce risk 
when the risk estimation for any potential hazard exceeds an acceptable level. The risk 
analysis for the eCoin system and the controller was performed early in the design 
process and has been updated throughout the process. The identified, anticipated risks 
were mitigated so that all potential hazards were reduced to an acceptable severity and 
occurrence.   
To verify mitigation of risk, the eCoin system has undergone testing for safety, essential 
performance, design verification and marking per applicable parts of IEC 60601-
1:2005+A1:2012(E) and ISO 14708-1:20000(E) as well as biocompatibility testing to be 
compliant with all applicable ISO 10993 standards.  
The table in attachment 4-15 is a summary of the potential risks to human health and 
traces them to specific FMEA assignments and risk mitigation measures.  
3-7-1-1 Clinical Safety Data as Validation of Risks  
The eCoin system has been used in a successful first in human feasibility trial from 2013 
through 2016 for the treatment of drug resistant hypertension in adults.  The system 
parameters were 2 pulses per second at a pulse width of 0.5 ms with amplitudes ranging 
from 0.5 mA to 25 mA.  There were no stimulation therapy related adverse events during 
this study. Section 2-2-2-1 is a summary of the safety results.  In this proposed study, 
the eCoin system parameters will be 20 pulses per second at a pulse width of 0.2 ms 
with amplitudes ranging from 0.5 mA to 15 mA.  The proposed system parameters 
match that utilized by many percutaneous tibial nerve stimulation studies for which no 
stimulation related adverse events were reported (3, 13, 17) and the same parameters 
used by FDA cleared devices (K132561) that also stimulate the tibial nerve for treatment 
of overactive bladder.  According to the American Urological Association’s guideline on 
the diagnosis and treatment of overactive bladder (34), percutaneous tibial nerve 
stimulation carried minor adverse events in reviewed studies.  The most frequently 
reported events were painful sensation during stimulation that did not interfere with 
treatment and minor bleeding at the insertion site.  In the panel’s view, benefits outweigh 
risks/burdens for the use of percutaneous tibial nerve stimulation in the thoughtfully-
selected and counseled patient who is highly motivated to make the office visits required 
for repeated percutaneous administration of tibial nerve stimulation. 
34. Gormley A, Lightner D, Burgio K, Chai T, Clemens JQ, Culkin D, Das A, Foster 
HE, Scarpero HM, Tessier C, Vasavada SP, Diagnosis and Treatment of 
Overactive Bladder (Non-neurogenic) in Adults: AUA/SUFU Guideline. American 

 
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Urological Association Education and Research 
https://www.auanet.org/education/guidelines/overactive-bladder.cfm 
3-7-2 Description of Patient Population 
The eCoin system is indicated for the treatment of patients with refractory urgency 
urinary incontinence.  For inclusion, subjects must meet the inclusion criteria and must 
not meet the exclusion criteria.  For more information about inclusion criteria, see 
Inclusion Criteria 3-3-2-2-1. 
Patients with overactive bladder have a clinically and statistically significant lower quality 
of life, lower depression status, and poorer quality of sleep (35).  Overactive bladder also 
causes additional health problems including increased risk of falls and fractures 
(presumably from nocturia in the elderly), urinary tract and skin infections, sleep 
disturbances and depression (36).  Most studies about the cost of overactive bladder 
focus on the economic burden of overactive bladder, showing a total cost to the US 
healthcare system of $26.3B a year (37).  Patients with refractory urgency urinary 
incontinence are those who are not achieving adequate control of incontinence 
symptoms through available modes of therapy.  Such modes include behavioral therapy, 
pelvic floor exercises, and pharmacological therapy. 
35. Stewart WF, Van Rooyen JB, Cundiff GW, Abrams P,Herzog AR, Corey R, Hunt 
TL and Wein AJ, Prevalence and burden of overactive bladder in the United 
States (NOBLE Study), World J Urol (2003) 20: 327–336. 
36. Brown JS, McGhan WF, and Chokroverty S, Comorbidities Associated With 
Overactive Bladder, The American Journal of Managed Care, Vol. 6, No. 11, 
SUP (2000), S574-S579. 
37. Wagner TH, Hu TW. Economic costs of urinary incontinence in 1995. Urology 
1998;51:355-361. 
3-7-3 Justification for Investigation 
3-7-3-1 Potential Benefits of Treatment 
According to the American Urological Association and its guideline for diagnosis and 
treatment of overactive bladder, the Panel interpreted the available percutaneous tibial 
nerve stimulation data to indicate that percutaneous tibial nerve stimulation can benefit 
a carefully selected group of patients characterized by moderately severe baseline 
incontinence and frequency and willingness to comply with regular return visits for 
administration of the percutaneous therapy.  The Grade C evidence supports a 
potential benefit of tibial nerve stimulation in overactive bladder patients of 
improvements to incontinence episodes, voiding volume, quality of life, frequency, and 
nocturia.  Furthermore, in a study by Finazzi-Agro et al., patients matching the 
population for the proposed study—females with detrusor overactivity incontinence—
showed statistically and clinically significant improvements in mean incontinence 
episodes per 3 days, mean voids per day, mean voided volume, and mean QoL score 
(17).  Thus, potential benefits of tibial nerve stimulation by eCoin include improvements 
to the number of incontinence episodes, voiding volume, frequency, and quality of life.    
3-7-4 Additional Safety Profile Information 
3-7-4-1 Description of Procedure  
eCoin is placed into a subcutaneous pocket in the lower leg. The anatomical structures 
involved in the implantation procedure are skin, subcutaneous tissue and fascia. The 

 
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eCoin sits above the fascia so the deeper structures are not affected. Within the 
subcutaneous pocket, there are no significant nerves or vessels, other than 
subcutaneous veins which are of minimal significance.  eCoin is placed about 3 mm 
above its target nerve (tibial nerve). 
Similar to other inert prosthetic devices, a fibrous capsule is expected to form around the 
eCoin system. This capsule stabilizes the implant at its desired location and 
compartmentalizes it from the surrounding tissues (skin, subcutaneous fat and fascia). 
3-7-4-2 Therapeutic or Stimulation Risks 
Although stimulation could briefly exceed a comfortable level during the activation 
procedure, no serious complications from tibial nerve stimulation are known or 
anticipated.  Stimulation pulses are charge balanced and at a charge density level 
known to be safe for neuromodulation with platinum electrodes (≤ 100 C/cm2). If 
stimulation intensity above the subject’s comfort level is reached during programming in 
the clinic, the subject may feel discomfort or pain until the stimulation level is turned 
down.  The subject may also experience a muscle twitch related to stimulation of the 
tibial nerve.  Discomfort or muscle twitch is managed through optimal setting of 
stimulation amplitude to subject comfort levels. Adjustments to stimulation levels are 
only made in the clinic where the patient response can be monitored and adjustments 
made as needed. 
Furthermore, the energy discharge of the eCoin battery is such that no harm will arise 
from heating due to a battery short. Direct shorting of the 120 mWh battery delivers less 
than 200 mW or 20 mW/cm2 of heat from the device surface to tissue. This ensures a 
safe level of tissue heating (less than 2 degrees Centigrade) in a worst case direct short 
failure condition. 
3-7-4-3 Risks of eCoin Implantation 
The most probable risks associated with eCoin implantation include ecchymosis, 
erythema, and incisional pain at the implant site, intermittent paresthesias of the toes, 
foot, or lower leg, and other wound healing complications. Other risks are categorized as 
uncommon or rare and are reported below: 
UNCOMMON (<5%)  
• 
Hematoma at the incision site 
• 
Implant site infection that leads to device explant 
• 
Persistent implant site pain  
• 
Severe pain during or shortly after the procedure 
• 
Persistent wound healing complications lasting beyond 8 weeks post implant 
• 
Persistent stimulation discomfort 
RARE (<1%) 
• 
Wound dehiscence  
• 
Allergic reactions to local anesthesia 
• 
Inflammation of nearby tendons 
• 
Localized neuritis  
• 
Surgical injury to adjacent nerves, vessels or tendons 
• 
Allergic reaction to implanted materials  
• 
Implant device failure leading to explant 
• 
Implant device extrusion 
• 
Implant device migration requiring explant or revision 
• 
Implant device inversion 

 
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Device-related risks of the eCoin system can be deduced from the 50 year field of 
neuromodulation.  The primary risks of importance are infection and lead-related 
problems (e.g. leadwire break, leadwire migration).  For the leadless eCoin system, lead-
related problems are not relevant.  The rate of infection can be reasonably estimated 
based upon other neuromodulation devices, an implantable device whose implantation 
site is nearby that of eCoin, and the OUS clinical study.  Infection can be mitigated 
through surgical training, adequate manufacturing controls, and adequate after-care 
instructions.  Infection can be resolved through explantation of eCoin and/or antibiotics. 
If needed, explantation of the eCoin device can be performed easily through simple 
opening of the capsule and removal of the device. If the capsule itself has a significant 
problem such as deep infection or dense scar tissue causing significant discomfort, then 
the capsule might require surgical excision, a procedure known as capsulectomy. 
In the OUS clinical study of eCoin, the rate of patient infections requiring explantation 
was approximately 4.2%. See 2-2-2-1 for details. 
The eCoin utilizes established biocompatible materials and manufacturing processes 
that are typical of implantable neurostimulators (titanium hermetic enclosure, silicone 
elastomer insulation coating (MED-4870) and with platinum stimulating electrodes). 
3-7-5 Standards Conformance Demonstrating Safety 
The eCoin system has been developed under design control in accordance with QSR 21 
820.30 and ISO 13485. 
3-7-5-1 Risk Management 
Risk management conforms to ISO 14971:2012(E). A Risk Assessment has been 
completed for the SNS system based on Use, Design and Process FMEAs (See Risk 
Assessment Report 110-1493 in attachment 4-14). 
3-7-5-2 Development Process and Design Verification Testing 
Safety, Essential Performance, Design Verification and Marking have been completed 
per applicable parts of IEC 60601-1:2005+A1:2012(E) in compliance with active 
implantable medical devices ISO 14708-1:2000(E) and software life cycles per IEC 
62304:2006. Attachment 4-16 is a summary of design verification testing results. 
3-7-5-3 Biological Evaluation  
The eCoin system is an active implantable device for long term patient contact duration 
(>30 days).  The eCoin system has been subject to biocompatibility testing in 
accordance with the ISO 10993 series of standards.  Biocompatibility compendiums 
were obtained from the suppliers of all materials to confirm that the supplier is also 
compliant with ISO 10993 requirements. The testing summarized in Table 3-2 was 
performed on sterile devices representing the final product using Good Laboratory 
Practices. Test Article Preparation was performed in accordance with ISO 10993-12. 
Based on the results of the in vitro testing, the eCoin Subcutaneous Neuromodulation 
System is safe and effective as an implant for the intended use. 
Standard 
Title 
Result 
ISO 10993-3:2003 
Biological evaluation of medical devices - Part 3: 
Tests for genotoxicity, carcinogenicity and 
reproductive toxicity.  
ISO Bacterial Mutagenicity Test – Ames Assay 
Mouse Lymphoma Assay 
Pass  
Pass 

 
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Standard 
Title 
Result 
ISO 10993-5:2009 
Biological evaluation of medical devices - Part 5: 
Tests for in vitro cytotoxicity. 
Cytotoxicity – Elution Test- MEM Extract 
 Pass 
ISO 10993-6:2007 
Subcutaneous Implantation Test – 90 days 
Systemic Toxicity Study of “SNS Biocompatibility 
Test Device” in Sprague Dawley Rats following 
Subcutaneous Implantation for 90 Days 
Pass 
Pass 
ISO 10993-7:2008 
/AC:2009 
Biological evaluation of medical devices -- Part 7: 
Ethylene oxide sterilization residuals. 
Pass 
ISO 10993-10:2010 
Biological evaluation of medical devices - Part 10: 
Tests for irritation and delayed-type hypersensitivity. 
Intracutaneous (Intradermal) Reactivity Test in New 
Zealand White Rabbits 
Maximization Test for Delayed-Type Hypersensitivity 
in Hartley Guinea Pigs 
Pass 
Pass 
ISO 10993-11:2006 
Biological evaluation of medical devices - Part 11: 
Tests for systemic toxicity 
Acute Systemic Toxicity Test in CD-1 Mice 
Pyrogen Test in New Zealand White Rabbits 
Pass 
Pass 
Table 3-2:  ISO 10993 Biocompatibility Testing 
3-7-5-4 Sterilization and Sterile Packaging 
The ethylene oxide sterilization process for the eCoin device was been developed, 
validated and is controlled per ISO 11135:2007 (see attachment 4-17). The sterile 
package sealing process and shelf life were developed and validated per ISO 11607 
(see attachment 4-18). 
 Description of the Device 
Valencia Technologies eCoin therapy for refractory urinary urge incontinence provides 
electrical stimulation to the tibial nerve from a small self-contained implant placed in the 
subcutaneous space over the tibial nerve in the lower leg.  Subjects receive the implant 
unilaterally in a simple procedure under local anesthetic. 
To stimulate the tibial nerve with the eCoin implant, the same parameters as previously 
demonstrated in animal and human studies are applied.  The stimulation rate is 20 
pulses per second (pps) at a pulse width of 0.2 ms. The stimulation pulse amplitude is 
adjusted to the highest comfortable level for the subject with an external controller. After 
activation, the implant automatically provides 30 minute stimulation sessions according 
to a fixed treatment interval schedule.  In between sessions, the amplitude can be 
adjusted or automatic therapy can be turned off.  The device contains a battery that will 
typically operate for 3 to 5 years before the device requires replacement.   
3-8-1 Components 
1) eCoin Implant – The implant is a coin-sized leadless battery powered device 23 mm 
in diameter and 2.2 mm thick. The electronics and battery are hermetically enclosed 

 
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in a titanium case. The materials in direct contact with tissue are the platinum 
electrodes, and the silicone elastomer jacket (NuSil MED 4870) that covers the 
titanium housing. Each implant receives a unique traceable serial number including 
labeling to place in recipient medical records. 
 
2) External Controller – The external controller programs the device via a magnetic field 
using a custom access code secured wireless protocol. 
 
3-8-2 Stimulation Settings/Parameters 
Amplitude Range: 0.5 up to 15 mA (programmable) 
Rate: 20 pulses per second (fixed) 
Pulse Width: 0.2 ms (fixed) 
Treatment Duration: 30 Minutes (fixed) 
Treatment Interval: 2 days for the first 12 weeks (42 sessions) and every 15 days 
thereafter (fixed)  
3-8-3 Implant Procedure 
Subcutaneous implantation of the eCoin is done under local anesthesia. The most 
prominent point of the medial malleolus will be palpated and marked. With the foot 
positioned at a 90-degree angle, a second marking is made 3 cm posterior to the medial 
malleolus marking. The implantation target location is found 3 cm cephalad to this 
second point along a line parallel to the posterior margin of the calcaneal tendon. 
Continuing on this line, the incision is made 3 cm cephalad to the target implantation 
site. The incision is made to the depth of the fascia with a width slightly smaller than that 
of the eCoin. Then, the eCoin is gripped with a surgical tool such as a needle driver or 
custom insertion tool, and slid on top of the fascia until it reaches the implantation site. 
The incision is then closed and dressed. See Attachment 4-2 for a complete surgical 
implant manual. 

 
Original Application for an Investigational Device Exemption 
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3-8-4 Activation of eCoin System  
After a 4 week period of implant healing, the eCoin devices are activated with the 
stimulation amplitude set to the subject’s upper most comfortable level.  Once activated, 
the eCoin applies a 30 minute session of neuromodulation therapy at the programmed 
amplitude every 2 days for a 12 week period and then every 15 days thereafter. 
3-8-5 Subject Compliance Monitoring  
eCoin Therapy:  Neuromodulation therapy is provided automatically by the implant 
system and has no compliance requirements.   
Drug Therapy: Subjects will be asked whether they are taking an overactive bladder 
medication through the primary endpoint to confirm that subjects are overactive bladder 
medication free.   
Data:  Compliance with voiding diaries is established through review by the clinical study 
coordinator at each center.  
Appointment Compliance:  Clinics’ designated study coordinators will ensure subjects 
are compliant with study appointments within the scheduling parameters outlined in the 
Visit Overview described in Section 3-4-2. 
3-8-6 Safety and Adverse Events  
3-8-6-1 Medical Monitoring  
The study will be approved by an independent ethical committee or institutional review 
board and subjects will be medically monitored by the participating Investigators. 
3-8-6-2 Definitions of Adverse Events 
Adverse Event (AE): Any untoward medical occurrence in a study participant whether 
or not there may be a causal relationship with this treatment / intervention.   This can 

 
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include (but is not limited to) worsening of subject’s overactive bladder condition and/or 
occurrence of serious sudden events. 
 
System and Procedure Related Adverse Event: Any device or placement procedure 
related adverse event.  This can include risks associated with the procedure, implant site 
or stimulation such as infection, or unexpected related adverse events that occur in 
relation to implant placement, median nerve stimulation or device failure.  The Sponsor 
maintains a list of expected adverse events and is responsible for determining 
expectedness.  
3-8-6-3 Classification of Events 
 Relationship 
YES- related:  The event has a reasonable possibility of a causal relationship to the 
administration of tibial nerve stimulation (procedure, device or stimulation) and no other 
etiology explains the event. 
 
NO- not related: The event is independent of tibial nerve stimulation (procedure, device 
or stimulation) and/or the event appears to be explained by another etiology. 
 Severity 
Mild: Transient or mild discomfort (<48 hours); no medical intervention/therapy required 
and does not interfere with the subject’s daily activities. 
Moderate: Some limitation in activity; some assistance may be needed; no or minimal 
medical intervention/therapy required. 
Severe: Marked limitation in activity; interrupts participant’s usual daily activity and may 
require medical intervention/therapy; hospitalization possible. 
Serious:  Results in death during the study period; is life-threatening; requires 
hospitalization or prolongation of existing hospitalization; results in persistent or 
significant disability or incapacity; results in a congenital anomaly or birth defect; 
requires medical or surgical intervention to preclude permanent impairment of a body 
function or to prevent permanent damage to a body structure, where the device is 
suspected to cause such intervention; other important medical events not captured by 
the other categories where the event may jeopardize the patient and may require 
medical or surgical intervention to prevent one of the other outcomes.  
 Expectedness 
Expected: Any adverse reaction whose nature and intensity are consistent with that 
described under risk assessment. 
 
Unexpected: Any adverse reaction not included under risk assessment. 
3-8-6-4 Recording of Adverse Events 
Expected device related AEs will be recorded on case report forms in Attachment 4-9, 
which are used at each visit.  Unexpected or unrelated AEs or any requiring medical 
attention will be checked on CRFs and further recorded on AE forms. Subjects will be 
requested to report adverse urologic events that are inconsistent with their normal 
medical condition that occur in between visits to the study coordinator or medical staff 
who will record on AE forms.  All adverse events will need to be evaluated and assigned 

 
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by a medical reviewer on or designated by the Data and Safety Monitoring Board 
(DSMB) with regards to: 
1) Relatedness or causality to the study device  
2) Severity  
3) Expectedness 
4) Action taken 
The Sponsor is responsible for determining if an adverse event is unexpected.  If 
expectedness is assessed by a medical reviewer as unexpected, the Sponsor will be 
notified and will evaluate and assign a final determination that may or may not result in 
reporting requirements. 
 
At each contact with the subject, the Investigator will obtain information on AEs by 
specific questioning and examination.   In the CRF for visits, if an event is reported, the 
AE checkbox will be selected.  This selection will trigger a separate form to be filled out 
which records the following information:  
1. Subject Number 
2. Adverse Event (AE) 
3. Date of AE onset 
4. Date of AE cessation 
5. Severity 
6. Expectedness 
7. Causality 
8. Was the patient hospitalized? If yes, provide dates. 
9. Will the patient continue with treatment, and will any be missed? 
10. Did the patient add or change any other associated medication and what 
were the changes/additions? 
11. Was there any other action taken? 
When an AE has been recorded, the PI or sub-PI for the study must sign and approve 
the assessment on the Sponsor provided form.  The Study monitor will keep track of the 
reported AEs.  A sample of the AE report form is in Attachment 4-9. 
3-8-6-5 Reporting Procedures 
For Serious Adverse Events (SAEs) or suspected Unanticipated Adverse Device Effects 
(UADEs), the Study Coordinator, the PI and the Sponsor will be alerted.  The timeline for 
medical review and assessment is 24 hours for SAEs and 7 days from subject reporting 
of non-Serious unexpected device related AEs.  For suspected UADEs the Sponsor will 
promptly provide an expectedness determination.  The Investigator must promptly inform 
the Ethics Board or IRB of SAEs or determined UADEs per local reporting requirements.  
 
The SAE form provided by the Sponsor should be completed and signed by the 
Investigator or physician sub-investigator and faxed or emailed to the Sponsor per the 
instructions on the form.  The entire SAE form needs to be completed, if possible, to 
make available in a timely manner complete relevant information thus limiting requests 
for additional information. Each SAE reported on an SAE form must also be reported in 
the adverse event section of the CRF. 
 

 
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These events will be reported by the Sponsor as appropriate to the regulatory authorities 
according to relevant jurisdictional medical device regulations. The Investigator will 
receive notification of these events across all study centers from the Sponsor. 
3-8-6-6 Adverse Event Reporting Period 
Adverse event information will be collected during the study duration - between Informed 
Consent and final follow-up.  If the patient presents to the Investigator after the study 
period and a device related AE is suspected, it should be reported to the Sponsor using 
the post study AE form provided by the Sponsor.  Post-study adverse events should be 
reported to the Sponsor after the study period if they are: 
1) AEs that are device related resulting in a reprogramming, revision surgery or 
explant (explant for reasons other than for normal end of life – e.g. battery 
depletion) for which the patient presents to the PI. 
2) AEs that occur during or related to an explant procedure performed at the normal 
device end of life.   
3-8-7 Subject Withdrawal & Termination 
3-8-7-1 Early Withdrawal of Subjects  
Subjects may voluntarily withdraw from the study for any reason at any time.  They may 
be considered withdrawn if they state an intention to withdraw, fail to return for visits or 
become lost to follow-up for any reason.  The devices must be recommended to be 
explanted if they are withdrawn. 
3-8-7-2 Terminating Subject Participation 
A subject’s continued participation in the study must be terminated for the following 
reasons: 
1) In the Investigator’s opinion, continued participation would be detrimental to the 
subject’s well-being. 
2) Subject is noncompliant with the protocol. 
3) Subject is lost to follow up (after 5 failed attempts to contact). 
4) Subject becomes pregnant during the trial. 
5) Subject uses prohibited treatments, medication changes, or procedures as 
defined in the exclusion criteria. 
The subject’s eCoin system must be recommended to be explanted if subject 
participation is terminated. 
3-8-7-3 Withdrawal/Termination Procedures 
If premature withdrawal occurs for any reason, the Investigator must make every effort to 
determine the primary reason for a subject’s premature withdrawal from the study and 
record this information on the Case Report Form for reporting to the Sponsor.  
Subjects enrolled in the study will not be replaced if they withdraw or are terminated from 
the study after device activation.  Provisions for device explantation will be arranged. 
3-8-7-4 Early Study Termination 
The study can be terminated at any time for any reason by Valencia Technologies.  
Should this be necessary, the subjects should be seen as soon as possible and treated 
as described in the early withdrawal section for a prematurely withdrawn subject.  The 
Investigator may be informed of additional procedures to be followed in order to ensure 

 
Original Application for an Investigational Device Exemption 
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that adequate consideration is given to the protection of the subjects’ interests.  The 
Investigator will be responsible for informing the IRB of the early termination of the trial.  
If required, provisions for the explant of the eCoin system will be arranged. 
3-8-7-5 Data Collection and Follow-up for Withdrawn Subjects  
Subjects will not be followed after completion of or withdrawal from the study. 
3-8-8 Data and Safety Monitoring Board 
A Data and Safety Monitoring Board of at least three members will review data including 
a monthly report of Adverse Events and data analyses at 1 months post implantation (a 
primary safety endpoint) and 3 months post activation (primary safety and efficacy 
endpoint). This DSMB will meet telephonically at least monthly until the study reaches 
the primary endpoint to review aggregate and individual subject data related to safety, 
data integrity and overall conduct of the trial.  They will be responsible for the review of 
safety endpoints.  The DSMB will provide recommendations to continue or terminate the 
trial depending upon this review.  A DSMB charter is set forth in a DSMB Charter 
document (see 4-10). 
 

 
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 Data Analysis Plan 
3-9-1 Data Collection 
All study data will be recorded onto Case Report Forms (CRFs) provided by Valencia 
Technologies. All CRFs will be completed using de-identified data. 
CRF completion may be delegated to other study personnel but the Investigator 
remains responsible for the accuracy and integrity of all data entered on CRFs. CRFs 
will be completed and sent to the designated representative for Valencia 
Technologies as directed, in an expedited fashion. All CRFs will be completed by 
study personnel only. Valencia or its designee will work with participating sites to 
secure data clarification and to obtain additional relevant medical documentation on 
participants enrolled into this trial.   
CRF’s for the study include: 
1) Screening  
2) Baseline 
3) Implantation 
4) Implant Healing Check 
5) eCoin Activation  
6) Safety Follow Up (1 month post-activation) 
7) Follow Up (2, 3, 4, 6 months post-activation) and long term monitoring (12 
months post-activation) 
8) Adverse Event 
9) Study Termination 
3-9-2 Interim Monitoring  
All clinical sites will be monitored periodically by Valencia Technologies or its 
designated representatives. Telephone contacts and site visits will be made 
throughout the course of the study. 
During site visits, the monitor will review participant records, device accountability 
and storage, general study procedures, and will discuss any problems with the 
Investigator. Monitors will audit data collected on CRFs and verify it against source 
documentation in accordance with the Clinical Monitoring Plan in Attachment 4.22. 
Monitors will confirm that written Informed Consent was properly obtained prior to 
enrollment of all participants. Any evident pattern of non-compliance will be 
addressed with the Investigator. If appropriate corrective actions are not subsequently 
undertaken, Valencia reserves the right to suspend enrollment at the site and/or 
withdraw the site from the study. 
At the close of the study at a research site, the clinical monitor will make a final on-
site visit. The purpose of this visit is to collect all outstanding study data documents, 
ensure that the Investigator's files are accurate and complete, review record retention 
requirements with the Investigator, make a final accounting of all study supplies 

 
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shipped to the Investigator, provide for appropriate disposition of any remaining 
supplies, and ensure that all applicable requirements are met for the study. 
 
3-9-3 Analysis Plan Summary 
This is a single-arm, prospective trial designed to demonstrate the safety and 
effectiveness of the eCoin tibial nerve neuromodulation system for the treatment of 
refractory urinary urge incontinence. A total of 50 subjects from about three to five 
different centers in New Zealand and the United States will be implanted with eCoin in 
the single arm study.  Up to 35 subjects from the United States will be implanted with 
eCoin. 
3-9-3-1 Primary Endpoint 
The primary endpoint of this study is the change in number of incontinence episodes 
from baseline to three months post-activation.  
Key Secondary Endpoints  
The key secondary endpoint is the percentage of responders in subjects implanted with 
the device.  Responders are defined as subjects with a 50% or greater reduction in urge 
incontinence episodes from baseline to three months post-activation.   
3-9-3-2 Exploratory Secondary Endpoints 
Estimate the difference in change from baseline in number of incontinence episodes at 
three and four months post-activation in all responder subjects with data available at 
three and four month visits.   
Estimate the change, expressed as a percentage from baseline, in incontinence 
episodes from baseline to three months post-activation in responder subjects.  
Estimate the change in number of micturitions from baseline to three months post-
activation in responder subjects.   
Estimate the change in mean voided volume from baseline to three months post-
activation in responder subjects.   
Estimate the change in I-QoL scores from baseline to three months post-activation in 
responder subjects.   
Patient satisfaction measured at 3 months post-activation. 
3-9-4 Primary Hypotheses 
The goal is to show the size of the treatment effect (reduction in leakage episodes) in 
responder subjects after three months of eCoin therapy. The null hypothesis is that 
there is no reduction in the mean number of leakage episodes from baseline after 3 
months of therapy.   
The primary effectiveness hypotheses being tested is: 
H0: µ(Subject) ≤  µ(Subject Baseline) 
 vs. 
H1: µ(Subject) > µ(Subject Baseline) 
Where µ(Subject) and  µ(Subject Baseline) are the mean number of leakage episodes  
at three months post-activation and at baseline. Rejection of the null hypothesis at a 
two-sided significance level of 0.05 indicates a mean reduction greater than zero. 
 

 
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3-9-5 Sample Size Calculation 
The sample size for this study is based on achieving adequate power to detect the 
size of the effect at 3 months post-activation.  The response variable is the change 
from baseline in the number of urge incontinent episodes after 3 months of therapy 
(3 months post-activation).  For the primary endpoint, urge incontinent episodes are 
measured prospectively using 3-day voiding diaries administered at baseline and 3 
months post-activation.  Subjects are required to have at least three urge 
incontinence episodes over 24 hours on a three-day voiding diary at baseline.  A 
sample size of 25 subjects provides 80% power to detect a true difference of 0.63 
leaks per day, assuming  the standard deviation in the in the response variable is 1 
leak per day with a two-sided 0.05 significance level.  The sample size assumes a 
10% loss to follow-up over the 3-months of treatment. 
3-9-6 Analysis Sets 
Efficacy analyses will be generated for the ITT, PP and Responder analysis sets, with 
the analysis on the Responder set being the primary analysis. Safety analysis will be 
performed on the safety analysis set. 
1) Responder: The subset of PP who achieve at least a 50% reduction in leakage 
episodes from baseline. 
2) Safety: All subjects implanted with the device.   
3) Intent-to-Treat (ITT): All enrolled subjects meeting the inclusion criteria of the 
study who are not ineligible because of exclusion criteria; this is a secondary 
analysis population for the efficacy endpoints and a primary analysis population 
for the safety endpoints. Missing outcome data will be handled per 3-9-9. 
4) Per-Protocol (PP): The subset of ITT subjects who complete the 3 month post 
activation follow-up period. 
3-9-7 Exploratory Subgroup Analyses 
Subjects who respond to treatment (i.e. who achieve at least a 50% reduction in number 
of leaks from baseline to three months post-activation) will be compared to non-
responders in terms of baseline characteristics and demographics as described in the 
statistical analysis plan.  Efficacy endpoints will be analyzed for the responder subset. 
3-9-8 Calculation of Efficacy Variables 
Change in Incontinent Episodes:  Incontinent episodes (IE) are measured 
prospectively using 3-day voiding diaries administered at baseline, 1, 2, 3, 4, and 6 
months post-activation of the eCoin system. 

 
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Change in Severity and Frequency of Leakage:  Severity and frequency of leakage is 
measured prospectively using 3-day voiding diaries administered at baseline, 1, 2, 3, 4, 
and 6 months post-activation of the eCoin system. 
Change in Frequency:  Frequency of urination is measured prospectively using 3-day 
voiding diaries administered at baseline, 1, 2, 3, 4, and 6 months post-activation of the 
eCoin system. 
Change in Voided Volume:  Voided volume is measured prospectively using a urine 
collection tool and captured using 3-day voiding diaries administered at baseline, 1, 2, 3, 
4, and 6 months post-activation of the eCoin system. 
Change in Quality of Life:  Quality of life is measured prospectively using the I-QoL 
questionnaires administered at baseline, 1, 2, 3, 4, and 6 months post-activation of the 
eCoin system. 
Patient Global Impression of Improvement: The level of patient satisfaction with the 
eCoin neuromodulation system will be rated by the subject on a descriptive scale of very 
much worse, much worse, worse, about the same, better, much better, and very much 
better. 
Patient Reported Satisfaction: The level of patient satisfaction with the eCoin 
neuromodulation system will be rated by the subject on a scale of 1 to 5 where 1 is Not 
at All Satisfied, 2 is Slightly Satisfied, 3 is Somewhat Satisfied, 4 is Very Satisfied and 5 
is Completely Satisfied. 
3-9-9 Missing Outcome Data 
Due to device implantation, few patient drop-outs are expected through primary and 
secondary endpoints.  Careful clinical planning that minimizes patient dropouts will be 
implemented.  
Multiple imputation per the statistical analysis plan will be used for missing data. 
3-9-10 Safety Analysis 
All AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). 
The terms included in the tabulations will be organ system and preferred terms.  
Tabulations of general AEs will be provided by treatment group by time point, and will 
include the number of subjects exposed, the number of subjects with at least one AE, 
and the number of subjects with at least one AE by organ system and preferred term. 
These tabulations will be repeated for all AEs recorded as having a causal relationship 
to investigational product. Tabulations of local AEs will be provided at 1 and 3 months, 
and will include the number of subjects exposed, the number of subjects with at least 
one AE, and the number of subjects with at least one AE by preferred term. Separate 
tables will be provided, if relevant, for SAEs or events leading to withdrawal from study. 
 
 

 
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 Data Handling, Record Keeping and Study Monitoring  
3-10-1 Confidentiality and Security 
The Investigator will ensure that the subject’s confidentiality is maintained on the CRFs 
or other documents submitted to the Sponsor. Subjects should be identified by their 
initials and a subject study number only.  Documents that are not for submission to the 
Sponsor such as the signed informed consent forms should be kept in strict confidence 
by the Investigator.  In compliance with ICH GCP Guidelines, it is required that the 
Investigator and institution permit authorized representatives of the company, of the 
regulatory agency(s), and the IRB direct access to review the subject’s original medical 
records for verification of study-related procedures and data.  Direct access includes 
examining, analyzing, verifying and reproducing any records and reports that are 
important to the evaluation of the study.  The Investigator will inform and obtain the 
consent of the subject to permit named representatives to have access to his/her study-
related records without violating the confidentiality of the subject.  Information about 
study subjects will be kept confidential and managed according to the requirements of 
the clinical sites regulatory authority.  As a part of the consent process, subjects will sign 
an authorization informing the following:  
 
What protected health information (PHI) will be collected from subjects in this study 
 
Who will have access to that information and why 
 
Who will use or disclose that information 
 
What rights does a research subject have to revoke their authorization for use of 
their PHI  
3-10-2 Training  
All study forms and procedures will be reviewed with medical/study staff at the 
participating centers.  Investigators or surgical designee will also be medically trained 
and certified by the Sponsor to perform the implant procedure.  Training will include any 
combination of cadaver training, video, or supervised procedures.  To perform the 
procedure the Investigator or designated medical doctor will need to be experienced in 
urology or uro-gynecology, and be certified by the Sponsor. 
3-10-3 Documentation, Case Report Forms and Source Documents 
All documents will be signed off by the Sponsor and controlled such that any revisions 
are approved and tracked, with each document identified with a document number and 
revision code.  Investigators will maintain the following items of documentation in the 
Investigator’s Study File on site: 
 
Protocol and any amendments 
 
Consent forms (sample, and subject signed and dated) 
 
IRB/ERC approval for the protocol and consent form 
 
Agreement letter sent to Sponsor 
 
Case Report Forms  
 
Adverse event or Problem reports to Sponsor and IRB 
 
Inventory control log 
 
Enrollment Log 
 
Records of deviations, violations, and amendments 
 
Implant Registration Cards, where required by local regulations 
Case Report Forms: All data requested on the CRF must be recorded.  All missing data 
must be explained.  If a space on the CRF is left blank because the procedure was not 

 
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completed or the question was not asked, select “N/D”.  If the item is not applicable to 
the individual case, select “N/A”.  If any entry error has been made, to correct such an 
error, draw a single straight line through the incorrect entry and enter the correct data 
above it.  All such changes must be initialed and dated.  DO NOT ERASE OR WHITE 
OUT ERRORS.  Case Report Forms will be kept in the Study File. 
Source Documents:  medical records, voiding diaries, QoL questionnaires, etc. will be 
maintained at the study clinic. 
3-10-4 Device Accountability 
Each device has a unique serial number assigned.  In the device box, there will be 2 
adhesive labels with the serial number of the device.  At the time of implantation, one 
sticker will be placed on the Implantation CRF and another sticker will be placed on the 
patient implantation card (see 4-7).  The Sponsor is responsible for managing the device 
accountability log across the study.  Each site will have a device tracker to be reconciled 
at the conclusion of the study. 
3-10-5 Monitoring Procedures, Auditing, and Inspecting  
A clinical research monitor will supervise conduct of the study at each site in 
accordance with the Clinical Monitoring Plan provided in Attachment 4-22. The monitor 
will visit the Investigator and the study facility at periodic intervals in addition to 
maintaining ongoing telephone, e-mail, and letter contact. The monitor will maintain up-
to-date personal knowledge of the study through observation, review of study records 
and source documentation, and discussion of the study with the Investigator and study 
personnel. The study site will assist the monitor by providing access to all relevant 
study materials. 
The clinical monitors will be qualified members of the Clinical Research Department of 
Valencia Technologies who have been trained on the study protocol, monitoring 
procedures, and standard operating procedures based on Good Clinical Practice and 
other applicable Federal regulations.  
The monitor’s responsibilities are: 
 
 
Conduct Site Initiation visit (after IRB approval/before first subject enrollment). 
 
Conduct periodic monitoring visits. 
 
Compare case report forms to source documents. 
 
Review Investigator’s files for accuracy, currency, and completeness. 
 
Ensure that informed consents are obtained. 
 
Ensure that IRB review is current. 
 
Ensure protocol compliance, document deviations. 
 
Prepare reports of visits. 
 
Ensure adverse events are reported. 
 
Conduct closeout visit (after all case report forms are received in house). 
 

 
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3-10-6 Protocol Deviations and Compliance 
3-10-6-1 Major Protocol Deviations 
A major protocol deviation is defined as one that affects the safety of the subject or the 
scientific validity of the results. 
1) A Physician Investigator can deviate from the protocol in an emergency situation, 
such as when a departure from the protocol is required to protect the life or 
physical well-being of a participant.  The Sponsor and the IRB/Ethics Committee 
must be notified as soon as possible, but not later than 5 days after the 
emergency situation occurred. 
2) Any non-emergency, major deviation to the protocol must be approved by the 
Sponsor and the IRB/Ethics Committee prior to implementation.  If a major 
deviation occurs that is not in response to the protection of a subject, without 
prior approval, the event is considered non-compliance.  Non-compliance must 
be reported to the IRB/Ethics Committee promptly – no later than 5 days after the 
deviation.  A PI’s failure to report promptly any major deviation for which the PI 
did not obtain prior approval is itself an incident of non-compliance and will be 
evaluated by the Sponsor and could be grounds for physician disqualification. 
3-10-6-2 Minor or Administrative Protocol Deviations 
A minor deviation is defined as one that does not affect the safety of the subject or the 
scientific validity of the results. If a minor deviation from the protocol is discovered, it 
should be noted on the protocol deviation log at the site and brought to the attention of 
the monitor at the next CRA visit.  These deviations do not need to be reported to the 
IRB/Ethics Committee.  Examples of a minor protocol deviation: 
1) Follow-up visits that occurred outside the protocol required time frame because 
of the participant’s schedule. 
2) Study procedure conducted out of timeframe, e.g. 3-day diary 
3) Participant failure to initial every page of the consent form 
4) Participant failure to return patient diary 
5) Copy of the ICF not given to the participant 
6) Missing original signed consent, but a copy exists 
7) Patient not given implant card 
3-10-6-3 Analyzing Deviations 
At each monitoring visit, the deviations log will be analyzed along with any additional 
deviations that might be discovered during the monitoring visit.  If any of the minor 
deviations are deemed to have an impact on the trial outcomes, this issue must be 
brought to the attention of the Sponsor.   
3-10-6-4 Statement of Clinical Compliance 
The study will be conducted in accordance with the design and specific provisions of this 
IRB/Ethics Committee approved protocol, in accordance with the ethical principles that 
have their origin in the Declaration of Helsinki, and that are consistent with Good Clinical 
Practice (GCP) and the applicable regulatory requirement(s). The Investigator will 
assure that no deviation from, or changes to, the protocol will take place without prior 
agreement from the Sponsor and documented approval from the IRB/Ethics Committee, 
except where necessary to eliminate an immediate hazard(s) to the trial participants. 
The Investigator will promptly report to the IRB/Ethics Committee and the Sponsor any 
changes in research activity and all unanticipated problems involving risk to human 
subjects, or others. 

 
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 Methods, Facilities, and Control Information 
3-11-1 Device Manufacturer 
3-11-1-1 Manufacturer name, address and contact information 
 
Name of device manufacturer: Valencia Technologies Corporation 
Address: 28464 Westinghouse Place, Valencia, CA 91355 
Contact Person: Dave Peterson, Chief Technology Officer  
Telephone Number: (661) 775-1414  
Fax Number: (661) 775-1411 
3-11-1-2 Manufacturer compliance with Subpart C, Design Controls 
(section 820.30), the Quality System Regulations (21 CFR Part 820) 
The eCoin Subcutaneous Neuromodulation System is manufactured by Valencia 
Technologies Corporation under design controls per QSR 21 820.30 and ISO 13485. 
3-11-1-3 Device Design and Manufacturing Information 
 Device Design 
Engineering drawings of the eCoin Subcutaneous Neuromodulation System described in 
section 3-8 are in attachment 4-19. Materials used outside of the hermetic package in 
the eCoin device are in attachment 4-20.  
Design inputs for the eCoin Subcutaneous Neuromodulation System include the 
requirements for functional performance and safety including applicable regulatory and 
legal requirements as well as the outputs of risk management. The design outputs for 
the eCoin Subcutaneous Neuromodulation System are captured in functional 
specification requirements. These design outputs are verified in the testing summarized 
in attachment 4-16 using test articles that are representative of the final product. The 
clinical use of the eCoin device has been validated in a successful first in human 
feasibility trial from 2013 through 2016 for the treatment of drug resistant hypertension in 
adults per the protocol in attachment 4-11.  
Design Reviews are conducted with representatives of functions concerned with the 
design and development stage being reviewed. Other specialist personnel are included 
as needed. Design changes arising from these reviews are verified and validated before 
approval and release. 
3-11-1-4 Manufacturing Controls 
Assembly procedures with test procedures are in place to ensure the eCoin device is 
produced in accordance with the design and performance specifications (attachment 4-
23). Each device is tracked individually by serial number with traceability to components 
and all production steps maintained in a device history record.  
3-11-1-5 Processing, Packaging, Storage 
The procedures for sterile packaging, sterilization and storage are in attachment 4-24. 
 
 
 

 
Original Application for an Investigational Device Exemption 
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 Study Sites and Investigators  
3-12-1 Organization and Participating Center 
3-12-1-1 Principal Investigators  
All U.S. based Principal Investigators participating in the study will have signed an 
Investigator Agreement, a template of which is enclosed as Attachment 4-21 in 
compliance with § 812.43. New U.S. based Principal Investigators will be required to 
sign the Investigator Agreement before being added to the study. Attachment 4-25 is the 
list of investigators.  
Sponsor 
Valencia Technologies Corporation 
Stacy Chambliss, Tel: +1 (661)775-1414 ext. 1002 
28464 Westinghouse Place 
Valencia CA, 91355 
United States 
3-12-2 Funding Source and Conflicts of Interest 
The study is funded by Valencia Technologies and participating centers will be paid 
according to clinical trial agreements.  No participating physicians are otherwise involved 
or have any ownership in the company. 
3-12-3 Institutional Review Board / Ethics Committees 
Institutional Review Board / Ethics Committees will approve the protocol for each 
respective center pursuant to center requirements or under an independent review 
board. 
 

 
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3-12-4 Roles and Responsibilities 
3-12-4-1 Investigator 
The following are the responsibilities of the Investigator: 
1) Assure IRB/Ethics Committee approval of protocol and informed consent is 
obtained.  
2) Follow the study protocol. 
3) Permit monitor to inspect facilities and records. 
4) Permit regulatory inspections of facilities and records, if necessary. 
5) Inform a patient of any risks and benefits associated with use of the device, and 
obtain the patient’s written consent for its use. 
6) Enroll subjects, execute study, transcribe data from source documents to Case 
Report Forms. 
7) Submit annual progress reports, final reports, and adverse event reports to 
IRB/Ethics Committee and to Sponsor. 
8) Return unused study articles, record their receipt, disposition, and return 
9) Refrain from promoting study or study articles in any manner that is not Sponsor 
authorized. 
10) Conduct study in accordance with the protocol. 
11) Track Sponsor provided inventory and assignments 
12) Maintain medical histories of subjects. 
13) Retain records for 10 years or as required by law following completion of the 
study. 
3-12-4-2 IRB/Ethics Committee 
The following are the responsibilities of the IRB or Ethics Committee, where one group 
will be designated by the center to perform the function: 
1) Review and approve, modify, or disapprove the study protocol and informed 
consent form. 
2) Receive continuing and final reports on study progress. 

 
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3-12-4-3 Sponsor  
The following are the responsibilities of the Sponsor: 
1) Submit protocol and informed consent to IRB/Ethics Committee and FDA and 
await approval. 
2) Submit proposed amendments to the protocol and informed consent to 
IRB/Ethics Committee and Regulatory Authority (where applicable and await 
approval, unless the change reduces the risk to subjects). 
3) Assure IRB/Ethics Committee and Regulatory Approval (where applicable) is 
obtained. 
4) Select and train monitors. 
5) Select and train Investigators and study personnel. 
6) Obtain agreement letter and c.v. of Investigator(s). 
7) Control shipment of test and control articles. 
8) Conduct overall administration of study. 
9) Investigate unanticipated, device-related adverse events. 
10) Document protocol deviations and violations. 
11) Report and respond to the DSMB. 
3-12-5 Subject Compensation 
Subjects will not be paid for participation in this study. However they will be provided a 
small stipend for travel and accommodation expenses associated with the study 
treatment and follow-up requirements. 
 Study Timetable 
Study initiation is planned for April 2017. Study enrollment of 100 subjects (to implant 50 
subjects) is expected to be completed by July 2017.  Study endpoints are expected to be 
reached for all subjects by end of November 2017. Monitoring is expected to be 
completed in August 2018. 

 
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4 Attachments  
 
 

 
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 3-day Voiding Diary 
 
 

 
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 Manuals, and Labels 
 

 
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 Investigator’s Brochure 

 
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 Patient Trial Brochure 

 
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 Informed Consent Document 
 
 
 
 
 
 
 
 
 
 

 
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 Patient Global Impression of Improvement 
 

 
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 Patient Implantation Card 
 

 
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 Case Report Forms 

 
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 Adverse Event Form 

 
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 DSMB Charter 

 
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 OUS Study for Hypertension Protocol 

 
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 OUS Study for Hypertension CRFs for Infections 

 
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 OUS Study for Hypertension DSMB Letter Recommending 
Suspension of Implantation at Site 12 

 
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 SNS Risk Assessment (110-1493) 

 
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 Summary of Risks and Mitigations 

 
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 Design Verification and Validation Reports 

 
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 Ethylene Oxide Sterilization Validation Reports 

 
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 Sterile Packaging Validation Report 

 
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 Engineering Drawings  

 
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 eCoin Device Materials 

 
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 Template Investigator Agreement 

 
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 Clinical Monitoring Plan 

 
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 Assembly Procedure eCoin Device 

 
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 Assembly Procedure Sterilization and Packaging Clinical 
Monitoring Plan 

 
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 List of Investigators 

 
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 303-1122 Software Design Specification SNS 

 
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 Biocompatibility Reports