SUBCUTANEOUS TIBIAL NERVE STIMULATION FOR URGENCY URINARY INCONTINENCE: A FOLLOW-ON STUDY
Phase: NA
Conditions: Overactive Bladder, Urge Incontinence, Incontinence, Urinary, Urinary Urge Incontinence
Sponsor: Valencia Technologies Corporation

 
Original Application for an 
Investigational Device Exemption 
 
 
13 March 2019 
 
SUBCUTANEOUS TIBIAL NERVE 
STIMULATION FOR URGENCY URINARY 
INCONTINENCE: A FOLLOW-ON STUDY 
 
Device Name:  
        eCoinTM (Electroceutical Coin) 
 
IDE Number: 
 
G170028/S003  
 
 
Sponsor & Manufacturer: 
Valencia Technologies Corporation 
 
 
 
 
 
28464 Westinghouse Place 
Valencia, CA 91355 
United States 
 
Principal Investigators:  
See Attachment 4-25 
 
 
 
 
CONFIDENTIAL 
Document Number 111-3335 Rev 1.2 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 2 of 93 
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 eCoinTM System ............................................................... 9 
 
EXECUTIVE SUMMARY OF NON-CLINICAL STUDIES .................................................................................................. 12 
2-3-1 
Bench Testing - eCoinTM Device ................................................................................................................... 12 
2-3-2 
Bench Testing External Controller ............................................................................................................. 16 
2-3-3 
MR Compatibility .............................................................................................................................................. 17 
2-3-4 
Electrical Safety and Electromagnetic Compatibility ........................................................................ 17 
2-3-5 
Electrical Safety and EMC External Controller ..................................................................................... 19 
2-3-6 
Software eCoinTM Device (209-1035, 209-1061, 303-1122) ............................................................ 19 
2-3-7 
Software External Controller (207-1541, 303-1122) ......................................................................... 19 
2-3-8 
Biocompatibility ................................................................................................................................................ 20 
2-3-9 
Particulate (Nelson Lab Number 884283-01)....................................................................................... 22 
2-3-10 Sterility (2002-1206) ....................................................................................................................................... 22 
2-3-11 Packaging (202-1254; Westpak 225-15-0053A) ................................................................................. 22 
2-3-12 Shelf Life (202-1254; Westpak 225-15-0053B, 225-15-0053C) ..................................................... 23 
3 
INVESTIGATIONAL PLAN.............................................................................................................................. 24 
 
PURPOSE .......................................................................................................................................................................... 24 
 
SUMMARY ......................................................................................................................................................................... 24 
 
PROTOCOL........................................................................................................................................................................ 25 
3-3-1 
Study Design ....................................................................................................................................................... 25 
3-3-2 
Subject Selection ............................................................................................................................................... 25 
3-3-3 
Ethical Considerations .................................................................................................................................... 25 
 
STUDY PROCEDURES ...................................................................................................................................................... 26 
3-4-1 
Recruitment Plans ............................................................................................................................................ 27 
3-4-2 
Visit Overview ..................................................................................................................................................... 28 
3-4-3 
Screening for Eligibility Procedures .......................................................................................................... 29 
3-4-4 
Prior and Concomitant Therapy ................................................................................................................. 30 
3-4-5 
Informed Consent Procedures ...................................................................................................................... 30 
3-4-6 
Baseline ................................................................................................................................................................. 30 
3-4-7 
Reimplantation of Subcutaneous Neuromodulation System ........................................................... 30 
3-4-8 
eCoinTM Activation ............................................................................................................................................ 31 
3-4-9 
Establishment of the Amplitude Setting .................................................................................................. 31 
3-4-10 Post Activation Follow-up Procedure ....................................................................................................... 31 
 
STUDY OBJECTIVES ......................................................................................................................................................... 31 
3-5-1 
Primary and Key Secondary Objectives .................................................................................................... 31 
3-5-2 
Secondary Objectives ....................................................................................................................................... 32 
 
RATIONALE FOR THE SELECTION OF OUTCOME MEASURES AND STUDY DESIGN ............................................... 32 
 
RISK ANALYSIS ................................................................................................................................................................ 33 
3-7-1 
Overview ............................................................................................................................................................... 33 
3-7-2 
Description of Patient Population .............................................................................................................. 34 
3-7-3 
Justification for Investigation ...................................................................................................................... 35 
3-7-4 
Additional Safety Profile Information ...................................................................................................... 35 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 3 of 93 
3-7-5 
Standards Conformance Demonstrating Safety ................................................................................... 37 
 
DESCRIPTION OF THE DEVICE....................................................................................................................................... 38 
3-8-1 
Components ......................................................................................................................................................... 39 
3-8-2 
Stimulation Settings/Parameters .............................................................................................................. 39 
3-8-3 
Implant Procedure ........................................................................................................................................... 39 
3-8-4 
Activation of eCoinTM System ........................................................................................................................ 40 
3-8-5 
Subject Compliance Monitoring .................................................................................................................. 40 
3-8-6 
Safety and Adverse Events ............................................................................................................................. 41 
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 
Sample Size Consideration ............................................................................................................................ 49 
3-9-5 
Calculation of Effectiveness Variables ...................................................................................................... 49 
3-9-6 
Missing Outcome Data .................................................................................................................................... 50 
3-9-7 
Additional OAB medications ......................................................................................................................... 50 
3-9-8 
Safety Analysis ................................................................................................................................................... 51 
 DATA HANDLING, RECORD KEEPING AND STUDY MONITORING ............................................................................ 52 
3-10-1 Confidentiality and Security ......................................................................................................................... 52 
3-10-2 Training ................................................................................................................................................................ 52 
3-10-3 Documentation, Case Report Forms and Source Documents .......................................................... 52 
3-10-4 Device Accountability ...................................................................................................................................... 53 
3-10-5 Monitoring Procedures, Auditing, and Inspecting ............................................................................... 53 
3-10-6 Protocol Deviations and Compliance ........................................................................................................ 54 
 METHODS, FACILITIES, AND CONTROL INFORMATION............................................................................................. 55 
3-11-1 Device Manufacturer ....................................................................................................................................... 55 
3-11-2 Organization and Participating Center ................................................................................................... 56 
3-11-3 Funding Source and Conflicts of Interest ................................................................................................. 56 
3-11-4 Institutional Review Board / Ethics Committees ................................................................................. 56 
3-11-5 Roles and Responsibilities.............................................................................................................................. 57 
3-11-6 Subject Compensation ..................................................................................................................................... 57 
 STUDY TIMETABLE ......................................................................................................................................................... 58 
4 
ATTACHMENTS ................................................................................................................................................ 59 
 
3-DAY VOIDING DIARY .................................................................................................................................................. 60 
 
MANUALS, AND LABELS ................................................................................................................................................. 61 
 
INVESTIGATOR’S BROCHURE ........................................................................................................................................ 62 
 
PATIENT TRIAL BROCHURE AND ADVERTISEMENT .................................................................................................. 63 
 
INFORMED CONSENT DOCUMENT ................................................................................................................................ 64 
 
PATIENT GLOBAL IMPRESSION OF IMPROVEMENT ................................................................................................... 65 
 
PATIENT IMPLANTATION CARD ................................................................................................................................... 66 
 
CASE REPORT FORMS .................................................................................................................................................... 67 
 
ADVERSE EVENT FORM ................................................................................................................................................. 68 
 DSMB CHARTER ............................................................................................................................................................ 69 
 OUS STUDY FOR HYPERTENSION PROTOCOL ............................................................................................................ 70 
 OUS STUDY FOR HYPERTENSION CRFS FOR INFECTIONS....................................................................................... 71 
 OUS STUDY FOR HYPERTENSION DSMB LETTER RECOMMENDING SUSPENSION OF IMPLANTATION AT SITE 
12 
72 
 SNS RISK ASSESSMENT (110-1493) ........................................................................................................................ 73 
 SUMMARY OF RISKS AND MITIGATIONS ...................................................................................................................... 74 
 DESIGN VERIFICATION AND VALIDATION REPORTS ................................................................................................. 75 
 ETHYLENE OXIDE STERILIZATION VALIDATION REPORTS ...................................................................................... 76 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 4 of 93 
 STERILE PACKAGING VALIDATION REPORT ............................................................................................................... 77 
 ENGINEERING DRAWINGS ............................................................................................................................................. 78 
 ECOINTM DEVICE MATERIALS....................................................................................................................................... 79 
 TEMPLATE INVESTIGATOR AGREEMENT .................................................................................................................... 80 
 CLINICAL MONITORING PLAN ...................................................................................................................................... 81 
 ASSEMBLY PROCEDURE ECOINTM DEVICE .................................................................................................................. 82 
 ASSEMBLY PROCEDURE STERILIZATION AND PACKAGING CLINICAL MONITORING PLAN ................................. 83 
 LIST OF INVESTIGATORS, CVS, AND CENTERS ........................................................................................................... 84 
 303-1122 SOFTWARE DESIGN SPECIFICATION SNS .............................................................................................. 85 
 BIOCOMPATIBILITY REPORTS ....................................................................................................................................... 86 
 BACTERIAL ENDOTOXINS TEST METHOD .................................................................................................................. 87 
 BIOBURDEN LEVELS AND RAW DATA ......................................................................................................................... 88 
 BATTERY RECEIVING INSPECTION INSTRUCTIONS.................................................................................................... 89 
 REFERENCES .................................................................................................................................................................... 90 
 ECOINTM FOR OAB FEASIBILITY: SAFETY .................................................................................................................. 91 
4-32-1 Adverse Event Table......................................................................................................................................... 91 
4-32-2 Subject 01-10 One Month Follow-up Implant Site Picture ............................................................... 91 
4-32-3 Subject 07-17 AE report ................................................................................................................................. 91 
 ECOINTM FOR OAB FEASIBILITY STUDY PROTOCOL ................................................................................................. 92 
 AFTERCARE INSTRUCTIONS .......................................................................................................................................... 93 
 
 
 
 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 5 of 93 
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).  Urgency urinary 
incontinence (UUI), which affects approximately one-third of patients with OAB, is 
associated with substantial negative effects on quality of life (HRQOL) (7). The 
unpredictable loss of urine and associated odor or related symptoms leads to well 
documented burden on quality of life. This study will focus on urgency urinary 
incontinence.  
 
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. A number of treatments, 
including first line behavioral therapies and second line medications (anti-muscarinics or 
oral β3-adrenoceptor agonists), are available; however, 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 Institute for Health and 
Clinical Excellence (NICE) in the United Kingdom and by the Food and Drug 
Administration in the United States. 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 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 6 of 93 
automated compliance, lower cost over device life compared with long-term visit costs, 
and improved efficacy through accurate device placement 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 Survey. 
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 Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 7 of 93 
2 Report of Prior Investigations  
 Prior Publications of Animal Studies 
The underlying science in support of tibial nerve stimulation for treatment of overactive 
bladder including urgency urinary incontinence has been well described in published 
scientific literature.  For example, in 1966, McPherson 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).  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 on to 
demonstrate a similar effect in the clinical setting in 16 patients (15).  Case studies on 
percutaneous tibial nerve stimulation (PTNS) for overactive bladder were then 
conducted followed by several 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.  The large diameter somatic afferent 
fibers of the tibial nerve cause inhibition of bladder activity by way of central inhibition of 
the micturition reflex pathway in the spinal cord or the brain. This action 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, the same spinal 
roots (L4-S3) appear to be 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.  Tai et al. showed 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), tibial nerve 
stimulation is likely to act on the PMC, either via the pelvic nerve or pudendal nerve or 
both. The pelvic nerve (S2-S4) controls bladder contraction (micturition) while the 
hypogastric (T10-L2) and pudendal (L4-S3) nerves control continence; stimulation of the 
large somatic afferent fibers of the tibial nerve, with spinal roots from L4-S3, is 
postulated to 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 Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 8 of 93 
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 
McGuire et al. (21) first described inhibition of detrusor activity by peripheral 
neuromodulation of the posterior tibial nerve. 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.  A meta-analysis by Gaziev et al. (25) showed level 1 evidence is available 
and supportive of the safety and effectiveness of tibial nerve stimulation for overactive 
bladder.  Data available on the safety of percutaneous tibial nerve stimulation show no 
major concerns for safety.  For example, in the 24-month follow-up study to the SUmiT 
trial, the authors found 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 Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 9 of 93 
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 eCoinTM System 
The eCoinTM system has been tested in a prospective, multicenter study on 46 subjects 
in the United States and New Zealand.  A review of the available data on both safety and 
effectiveness of eCoinTM when implanted next to the tibial nerve for treatment of urgency 
urinary incontinence (UUI) is set forth in subsections 2-2-2-1 and 2-2-2-2. 
The Valencia Technologies eCoinTM system was tested in a prospective, multicenter 
study to confirm the effectiveness and safety of median nerve stimulation using bilateral 
eCoinTM devices in resistant or drug-intolerant hypertensive human subjects. A review of 
the data on safety of eCoin when implanted in the periphery subcutaneously is given in 
subsection 2-2-2-3.  
2-2-2-1 Effectiveness of eCoinTM Tibial Nerve Stimulation for UUI 
 
The feasibility study of eCoinTM tibial nerve stimulation enrolled and implanted 46 
subjects. Two subjects (08-07 and 07-06) did not complete an adequate baseline diary 
or follow-up diaries.  Age may have been a factor in the inadequate diary completion: 
both subjects were 78 years old.  A third subject (07-17) was explanted prior to receiving 
treatment (device activation).  The following analysis excludes data from those three 
subjects. 
 
As of the time of this writing, all 43 subjects have reached three months of follow-up—
the primary endpoint and the time point for all data presented herein.  With an average 
baseline of 5.25 ± 2.93 urge leaks per day, the average change at 3 months is -3.30± 
2.99 (N=43) urge leaks per day.  The average percentage change in urge leaks in 
comparison to baseline is -61%.   
 
Ten of the 43 subjects (23%) showed no urge leaks (i.e., a 100% improvement); 19 
(44%) showed at least a 75% improvement in urge leaks, and 30 (70%) showed at least 
a 50% improvement. 
 
Patient reported outcomes also showed improvement.  Specifically, 72% of subjects (31 
of 43) report improvement of at least 10 points in their quality of life as measured by the 
Incontinence Quality of Life Questionnaire (iQoL).  Similarly, the average score on the 
Patient Global Impression of Improvement (PGI-I) scale, which was measured on a 
scale of 1 to 7 from very much worse to very much better, was 5.44.   

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 10 of 93 
 
In conclusion, the objective diary data and patient reported data show promise for 
eCoinTM as a treatment of UUI.     
2-2-2-2 Safety of eCoinTM Tibial Nerve Stimulation for UUI 
 
The feasibility study of eCoinTM tibial nerve stimulation implanted 46 subjects; the last 
implantation procedure was performed on October 1, 2017.  At the time of this writing, all 
subjects have had the device implanted for at least six months, where one month is the 
critical period for the incident of expected related adverse events in a leadless 
neurostimulator.  All subjects have also reached the primary endpoint of 3 months.  Per 
protocol, subjects attend an incision check visit two weeks after implantation. They then 
attend a visit one month after implantation at which the wound is reviewed again and 
programming is done.  The safety data presented herein reflect all reported and known 
safety data to date. 
 
Thirteen (13) related adverse events (AEs) and three serious adverse events (SAEs) 
(one related [SAE#1] and two unrelated [SAE #2 and [SAE#3]) have occurred.  For 
purposes of this section, “related” includes “possibly related” as well as “related”.  See 
table of related adverse events in Attachment 04-32. All the AEs have now been 
resolved.  Subject 01-10’s adverse event of mild swelling and Subject 03-05’s incidence 
of mild to moderate swelling and ankle pain that were previously reported as ongoing are 
now resolved. 
 
The related serious adverse event (SAE #1; Subject 07-17) involved severe cellulitis of 
the subject’s calf secondary to the ankle wrap.  See Attachment 04-32 for the SAE report 
including the hospital report.  The subject was admitted to the hospital with infection and 
given IV antibiotics.  The infection was resolved with antibiotics.  Nonetheless, the 
subject desired to have the device explanted, which was done November 1, 2017.   
 
The second serious adverse event (SAE #2) was a limp on the leg where the device was 
implanted.  The subject, a patient who did not respond to the therapy and who had 
peripheral edema at screening, desired to have the device removed.  The device was 
successfully removed on December 7, 2017.  The patient returned for an incision healing 
check on December 21, 2017.  The SAE is now resolved with no sequelae.  Both the 
center and the DSMB later categorized the SAE #2 as unrelated.  Subject also had 
bursitis of the hip, which was inflamed, responded to injections, and later returned once 
effect of injections had worn off. 
 
The third SAE (SAE#3 of 3) was an unrelated incident of pneumonia that resolved. 
 
Finally, there were two slightly misplaced devices (up to one centimeter) at one New 
Zealand center noticed by the DSMB during review of photographs taken at the subjects’ 
healing check visits.  An investigation was opened to determine how the misplacements 
occurred and to decide whether the center should continue implantations.  The DSMB 
determined that the center had not used a measurement tool optimally.  In response, the 
surgical trainer retrained the appropriate PI on this tool, updated and clarified the 
surgical manual, and communicated with all PIs on the correct use of the measurement 
tool.  The DSMB was satisfied that actions taken would prevent further misplacements 
and allowed continued implantations at the affected center.  The Sponsor believes that 

 
Original Application for an Investigational Device Exemption 
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proctoring of all first implants, as done in the United States where no misplacements 
occurred, provides assurance that all devices will be optimally placed.  
 
In summary, the safety data suggest that the primary concern is mild to moderate wound 
healing, which resolved in all cases.     
2-2-2-3 Safety of eCoinTM Median Nerve Stimulation for Hypertension 
The global multicenter feasibility study on hypertension is complete and thus the safety 
data are available for review and presented herein.  Among the 48 subjects with 96 
implanted eCoinTM devices, two related Serious Adverse Events (SAEs) (called out as 
“SAE #1” and “SAE #2” in this Section) occurred.   
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 six months post implant and led to the explant of the device (SAE #1). 
Three of the four infections occurred at 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 (SAE #2). All remaining Adverse 
Events were judged to be unrelated to the device or therapy. 
Attachment 4-12 presents the case report forms for the four reported infections.  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 subjects who had adverse events of infection or were explanted 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 a 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 the device from the right 
arm.  The corresponding adverse event logs, organized according to patient number, are 
enclosed. 
The DSMB investigation into the higher than average infection rate 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 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. 
2-2-2-4 Conclusions 
Adverse events related to the eCoinTM therapy are associated primarily with inflammation 
or infection at the implant site. In the completed hypertension feasibility study on 48 
subjects with bilateral implants, two subjects had related SAEs (one infection and one 
unconfirmed infection), both of which were resolved by explant of the device.  
In the ongoing OAB feasibility study on 46 subjects, all subjects have been followed at 
least six months post-operatively and the safety results appear slightly better than the 

 
Original Application for an Investigational Device Exemption 
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Study 
 
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aforementioned hypertension study.  One subject had a related SAE (severe cellulitis of 
the calf secondary to ankle wrap provided for post-operative care), and two subjects had 
unrelated SAEs (one pneumonia and one limp associated with underlying bursitis of the 
hip and peripheral edema present at screening).  The other adverse events were 
associated primarily with wound healing, all of which were resolved. 
 Executive Summary of Non-Clinical Studies 
Preclinical testing of the eCoinTM subcutaneous neuromodulation system has been 
performed to assure conformance to the design specifications. 
The eCoinTM 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 - eCoinTM Device 
The eCoinTM 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 eCoinTM 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 eCoinTM device is no more than 1.5%. This test was repeated on eCoinTM 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 
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Study 
 
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2-3-1-3 Temperature Exposure (207-1093 2.3.4, 202-1254) 
The eCoinTM 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, eCoinTM 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 eCoinTM 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 eCoinTM 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 eCoinTM 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 
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Study 
 
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2-3-1-7 Mechanical Squeeze Test (207-1093 2.3.9)  
The eCoinTM 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 eCoinTM 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 eCoinTM 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 eCoinTM device passed final functional test following a 10 second exposure to a 
conducted 500 kHz sine 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 eCoinTM 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. 
 
2-3-1-11 Corrosion Test (207-1093 2.4.1)  
No corrosion of the eCoinTM 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. 

 
Original Application for an Investigational Device Exemption 
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Study 
 
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2-3-1-12 Battery Service Life and Elective Replacement (207-1082 2.6, 2.7; 
201-1016, 201-1111)  
The eCoinTM 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 eCoinTM 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 eCoinTM 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. 
2-3-1-15 Laser Seam Weld Validation (202-1436)  
The eCoinTM 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.”  

 
Original Application for an Investigational Device Exemption 
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Study 
 
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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. 
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. 

 
Original Application for an Investigational Device Exemption 
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Study 
 
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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 eCoinTM Subcutaneous Neuromodulation System has not been evaluated for safety 
and compatibility in the MRI environment and is considered MRI unsafe. Patients with 
the eCoinTM implant should not undergo Magnetic Resonance Imaging (MRI). 
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 eCoinTM 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. 

 
Original Application for an Investigational Device Exemption 
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Study 
 
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2-3-4-2 Current Leakage (207-1093 2.3.10)  
The direct current leakage between the anode and cathode of the eCoinTM 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 
eCoinTM 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 eCoinTM 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 
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Study 
 
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CONFIDENTIAL                                               Page 19 of 93 
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 eCoinTM Device (209-1035, 209-1061, 303-1122)   
The level of safety concern for the eCoinTM 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 
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Study 
 
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CONFIDENTIAL                                               Page 20 of 93 
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 eCoinTM test article extract, the 
eCoinTM 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 eCoinTM 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 eCoinTM test 
article when compared to control. Under the conditions of the study, the eCoinTM 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 eCoinTM test article extract exhibited a greater 
biological activity when compared to those treated with the control. Under the conditions 
of the study, the eCoinTM 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 
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Study 
 
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CONFIDENTIAL                                               Page 21 of 93 
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 eCoinTM 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 eCoinTM test article were within limits defined for a negative 
response. Accordingly, the eCoinTM 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 eCoinTM 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 Urgency Urinary Incontinence: A Follow-on 
Study 
 
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CONFIDENTIAL                                               Page 22 of 93 
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 eCoinTM device was less than 0.012 mg (1.2 
micrograms per centimeter squared of device surface area). The ethylene chlorohydrin 
residual for the eCoinTM 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 eCoinTM 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 eCoinTM device ethylene oxide sterilization process was validated per ISO 11135 
using half cycle batch release approach with 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 eCoinTM 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.”  

 
Original Application for an Investigational Device Exemption 
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File 2: “003_Appendix B Test Lab Report No 225-15-0053A”  
2-3-12 Shelf Life (202-1254; Westpak 225-15-0053B, 225-15-0053C) 
Accelerated and real time aging of the eCoinTM 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 eCoinTM 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 
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3 Investigational Plan  
 Purpose 
This investigation is designed as a follow-on study to a feasibility study called, 
“Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence” (“the eCoinTM 
Feasibility Study for Urgency Urinary Incontinence”). The purpose of this follow-on study 
is to collect data on the reimplantation of the study device, eCoinTM.   
 
Valencia Technologies Corporation, the Sponsor, manufactures the study device, 
eCoinTM (electroceutical coin).  eCoinTM is an investigational device to be utilized in the 
treatment of patients with urgency urinary incontinence (UUI).   
 
Up to 30 subjects will be consented and enrolled to participate in the follow-on study.  
Only subjects meeting all inclusion and exclusion criteria will be enrolled. 
 
Each person will participate in the follow-on study for up to 39 weeks (up to 15 weeks 
between screening and device activation plus 24 weeks of follow-up). Participants from 
New Zealand will have one additional follow-up visit 3-years post-activation. 
The primary aims are to evaluate the safety and effectiveness of reimplantation of the 
eCoinTM for the treatment of UUI. 
 Summary 
This prospective, multicenter, single-arm follow-on study will evaluate the safety and 
effectiveness of eCoinTM tibial nerve stimulation in subjects with urgency urinary 
incontinence (UUI) as defined by the American Urological Association (30). The follow-
on study will evaluate changes from baseline in OAB symptoms as measured by voiding 
diaries and patient-reported outcomes through 24 weeks of eCoinTM therapy (which is 
the same as 28 weeks from study device reimplantation).  The primary outcome will be 
measured at 12 weeks of eCoinTM therapy; the key secondary outcomes will be 
measured at 24 weeks of eCoinTM therapy. Safety will be summarized by data on 
reportable adverse events and device deficiencies. Participants from New Zealand will 
have one additional follow-up visit 3-years post-activation. 
 
The eCoinTM neuromodulation device will be reimplanted subcutaneously in the right or 
left leg of subjects with UUI.  After a 4-week implant healing period, all subjects will have 
a programming visit where the device is activated (turned ON).  After 12 weeks 
(occurring about 16 weeks post-reimplantation), the primary effectiveness and primary 
safety endpoints will be assessed.    
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 
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Study 
 
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 Protocol  
3-3-1 Study Design 
This trial is a prospective, multicenter, single-arm follow-on study of the safety and 
effectiveness of eCoinTM tibial nerve stimulation in subjects having UUI.  
 
Subjects will be screened. Up to 30 subjects who meet all inclusion and exclusion 
criteria will be enrolled to participate.  All subjects will be scheduled to receive the 
investigational therapy (eCoinTM for UUI).   
 
This document may refer to eCoinTM as “eCoinTM,” “eCoinTM therapy”, the “eCoinTM 
system,” or the “study device.”  All such terms refer to the active study device called 
eCoinTM by the manufacturer. 
3-3-2 Subject Selection  
3-3-2-1 Patient Population 
The primary sample size target is 30 subjects having UUI who participated in the 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence feasibility trial. 
The baseline assessment from the feasibility trial, which included complete medical 
history, physical examination, and completion of a 3-day voiding diary to quantify voiding 
behavior, symptoms, and incontinence, will serve as the baseline for this follow-on study. 
Only subjects who meet all the inclusion and exclusion criteria, and have provided 
informed consent, will be enrolled. 
 
All eligible enrolled subjects will be scheduled to be reimplanted with the eCoinTM 
system. The investigator will select the side of reimplantation. Approximately 4 weeks 
post reimplantation, subjects will return for a programming visit at which time the device 
will be activated. A programming technician will implement the activation procedure, 
setting amplitude of stimulation according to a comfortable level. 
 
3-3-2-2 Selection Criteria 
Participants shall be screened in accordance with the following inclusion and exclusion 
criteria.  
 Inclusion Criteria 
1. Individual participated in the eCoinTM Feasibility Study for Urgency Urinary 
Incontinence. 
2. Individual was implanted with the study device during the eCoin Feasibility Study 
for Urgency Urinary Incontinence. 
3. Individual is able to give his or her written, informed consent. 
4. Individual is mentally competent and able to understand all study requirements. 
 Exclusion Criteria 
1. 
Individual is pregnant or intends to become pregnant during the study. 
 
3-3-3 Ethical Considerations  
This follow-on study involves no critical ethical issue. Subjects who are refractory to 
second- or third-line therapy have the potential to gain a new treatment modality through 

 
Original Application for an Investigational Device Exemption 
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Study 
 
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participation in the follow-on study and to assess the impact of this treatment modality on 
their incontinence with minimal risk.   
• 
All subjects will receive tibial nerve stimulation with the eCoinTM device. The 
subjects will be followed for 24 weeks post-activation, and will keep the device 
thereafter, offering them an opportunity to continue using an investigational 
therapy that might provide benefit. The follow-on study Sponsor will pay for 
removal of the device by the study center occurring up to three years from its 
reimplantation in this follow-on study. 
• 
While other device modalities are more invasive (i.e., sacral neuromodulation or 
botulinum toxin of the bladder) and drug therapy is fraught with poor compliance, 
as an investigational device, the follow-on study will only include patients who 
have an inadequate response to second- or third-line therapies.   
• 
Some subjects may not receive clinical benefit from eCoinTM therapy, but are to 
continue with follow-up until follow-on study completion even if they ask for 
eCoinTM to be explanted. Some individuals who initially do not receive clinical 
benefit may benefit from late response and cumulative effects of treatment. That 
said, subjects included in this follow-on study have already received the study 
device and chosen to receive another study device in this follow-on study of the 
reimplantation of the study device. 
• 
Subjects are not required to wash off or stay off pharmacological medications for 
overactive bladder. It is unlikely that subjects will be taking pharmacological 
medications for overactive bladder during this follow-on study, but if they are, 
such information will be tracked. If the addition of medications is medically 
necessary as described herein, such information will be collected and reported. 
 Study Procedures 
All subjects will be followed for 24 weeks post-activation (which is the same as 28 weeks 
post-reimplantation).  A 3-day voiding diary will be collected that reports the number and 
type of incontinence episodes, number of micturitions; and administering questionnaires 
including the IQoL, and PGI-I at 12- and 24-weeks post-activation. Participants from 
New Zealand will have one additional follow-up visit 3-years post-activation. The 3-day 
voiding diary and questionnaires will again be provided at this 3-year follow-up visit. 
At the time of screening, a photo of the implant site from the feasibility will be taken 
according to the Implant Verification Photos Protocol. 
The follow-up study visits are described in relationship to the initial activation visit 
occurring 4 weeks after reimplantation of the study device. Thus, 28 weeks post-
reimplantation occurs at the 24 weeks post-activation visit, and 16 weeks post-
reimplantation occurs at the 12 weeks post-activation visit.  See Visit Overview 3-4-2 for 
exact timing of such visits. For any enrolled subject who is not activated, the same 
schedule will be followed as if the subject were activated.    
Subjects are not required to wash off or stay off of pharmacological medications for 
overactive bladder. As this trial is a follow-on to the feasibility study, it is unlikely that any 
individual will be taking pharmacological medications for OAB, but if they are, such 
information will be recorded.  

 
Original Application for an Investigational Device Exemption 
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Study 
 
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The battery of the device is expected to last between 2 and 3 years. The study sponsor 
intends to remove, and will cover the cost of device explantation up to three years from 
the eCoin activation date in this follow-on study. Should a participant elect not to have 
their device removed by this time, they will be without Sponsor coverage for a future 
explantation procedure. 
 
 
3-4-1 Recruitment Plans 
Subjects who participated in the eCoinTM Feasibility Study for Urgency Urinary 
Incontinence will be contacted by the investigator or designated study staff and 
presented with the opportunity to participate in the follow-on study, including: 
 
• 
reason for being identified (participation in the eCoinTM Feasibility Study for 
Urgency Urinary Incontinence) 
• 
description of therapy 
• 
potential benefits 
• 
potential risks 
• 
compensation (see 3-11-6)  
 
Patients who remain interested will be brought into the research clinic for further 
screening and informed consent.   
 
 
 

 
Original Application for an Investigational Device Exemption 
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Study 
 
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3-4-2 Visit Overview 
The ordered enrollment process consists of screening (including obtaining written 
consent), reimplanting the eCoinTM system, and establishing the participant’s amplitude 
setting. This Section includes a table of the visit schedule and contents thereof.  The 
timing of visits 1 through 3, 8 and 9, is described in relationship to the visit named, while 
the timing of visits 5, 6, and 7 is described in relationship to the initial activation visit 
(Visit 4).  
 
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 telephone 
call to remind them of the diary requirement at least 3 days prior to each follow-up visit.   
• 
Visit 1: Screening Procedures (history and physical examination, informed 
consent, eligibility determination, concomitant medication therapy review, implant 
location photo) 
• 
Visit 2: Reimplantation Procedure (Time: Between 0 and 60 days from Visit 1): 
adverse event assessment, concomitant therapy review, pre and post-op pictures 
• 
Visit 3: Incision Healing Check (week 2) (Time: Between 9 and 19 days from Visit 
2) including pictures 
• 
Visit 4: Initial Activation (week 4) (Time: Between 23 and 43 days from Visit 2) 
including pictures 
• 
Visit 5 (12 weeks post-activation): Follow-up Assessments (3-day voiding diary, 
adverse event assessment, concomitant medication therapy review, patient 
surveys including IQoL, patient satisfaction, and patient global impression of 
improvement) (Time: Between 79 and 89 days from Visit 4) 
• 
Visit 6 (24 weeks post-activation): Follow-up Assessments (3-day voiding diary, 
adverse event assessment, concomitant medication therapy review, patient 
surveys including IQoL, patient satisfaction, and patient global impression of 
improvement) (Time: Between 163 and 173 days from Visit 4) 
• 
(New Zealand participants only) Visit 7 (3 years post-activation):  
Follow-up Assessments (3-day voiding diary, adverse event assessment, 
concomitant medication therapy review, patient surveys including IQoL, patient 
satisfaction, and patient global impression of improvement) (Time: Between 2.5 
and 3 years from Visit 4) 
• 
Visit 8: Explant Visit (Time: Between 0 days from Visit 6 and up to 3 years from 
Visit 4) including pre and post-op pictures 
• 
Visit 9: Incision Healing check (2 weeks post-explantation): visit to assess wound 
healing including pictures. (Time: Between 9 and 19 days from Visit 12) 
 
 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 29 of 93 
 
 
Screening 
Reimplantation 
Incision Healing Check 
Activation (Follow up Clock Starts) 
12 Week Follow-Up 
24 Week Follow-Up: Primary Endpoint 
3 Year Follow-Up (NZ Participants) 
Explant Visit 
Incision Healing Check 
Demographics, screening exam, physical 
exam, & medical history 
X 
 
 
 
 
 
 
 
 
Eligibility Determination 
X 
 
 
 
 
 
 
 
 
Informed Consent 
X 
 
 
 
 
 
 
 
 
Picture Taken of Incision Site 
X 
 
X 
 
 
 
 
X 
X 
3-day Voiding Diary Reminder Call 
 
 
 
 
X 
X 
X 
 
 
3-day Voiding Diary 
 
 
 
 
X 
X 
X 
 
 
IQoL Assessment 
 
 
 
 
X 
X 
X 
 
 
Patient Reported Satisfaction Assessment 
 
 
 
 
X 
X 
X 
 
 
Patient Global Impression of Improvement 
 
 
 
 
X 
X 
X 
 
 
Implant or Explant Procedure  
 
X 
 
 
 
 
 
X 
 
Incision Assessment  
 
 
X 
 
 
 
 
 
X 
Initial Activation 
 
 
 
X 
 
 
 
 
 
Completion of Primary Endpoints 
 
 
 
 
X 
 
 
 
 
Completion of Study 
 
 
 
 
 
X 
 
 
 
Subject Assessment for AEs 
 
X 
X 
X 
X 
X 
X 
X 
X 
    Figure 3-1: Summary of Study Process 
3-4-3 Screening for Eligibility Procedures 
Interested adults who participated in the eCoinTM Feasibility Study for Urgency Urinary 
Incontinence will be eligible to participate.  
Subjects who initially qualify will be scheduled for a screening visit to assess general 
health.  Subjects will 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. A photo of the implant site from the feasibility will be taken according to 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
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the Implant Verification Photos Protocol. After patients provide their informed consent, 
they may be scheduled for reimplantation of the study device.  
3-4-4 Prior and Concomitant Therapy  
The use of agents for overactive bladder will be reported at screening and at each 
follow-up visit.  It is anticipated that most subjects will not be on overactive bladder 
medications because they participated in the eCoinTM Feasibility Study for Urgency 
Urinary Incontinence. 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 follow-on study as described in the Informed Consent Form (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 their 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 move forward for scheduling the reimplantation. 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. The signed 
Informed Consent Form shall be included in the patient’s medical record file and noted in 
the screening CRF.  
3-4-6 Baseline  
The baseline assessment completed during subject’s participation in the eCoinTM 
Feasibility Study for Urgency Urinary Incontinence will serve as the baseline for this 
follow-on study. Furthermore, subjects that are enrolled in this study will retain their 
subject ID numbers from the previous feasibility study. 
 
3-4-7 Reimplantation of Subcutaneous Neuromodulation System  
Subjects who are approved are to undergo a reimplantation procedure following, but no 
later than, 120 days from screening. The eCoinTM system will be reimplanted in 
accordance with the procedures outlined in the Surgical Implant Manual set forth in 
Attachment 4-2 for Manuals and Labels. The reimplantation procedure is conducted as 
an outpatient procedure under local anesthesia for subcutaneous placement. An incision 
site healing check will be performed 2 weeks post reimplantation. 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. Telephone 
numbers will be obtained from the participant at the time of informed consent to ensure 
the clinic is able to contact the subject and primary physician as needed. Patients will be 
instructed on post-procedural wound care and limitation of certain physical activities.  
Antibiotics and pain medication will be prescribed at the discretion of the investigator.  
3-4-8 eCoinTM Activation  
All subjects will return for a device activation visit four weeks after reimplantation.  At this 
point, the follow-up visit clock will start to run (that is, the follow-up visits will be 
characterized in relationship to the date of the activation visit).   

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
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The subject will be provided with a 3-day voiding diary to complete in the 7 days prior to 
the next visits (occurring 12- and 24-weeks post-activation, and also 3 years post-
activation for New Zealand participants). At least 3 days prior to the next visit, a member 
of the study staff will telephone subjects to remind them that they should begin the 3-day 
diary.  
 
3-4-9 Establishment of the Amplitude Setting 
The programming technician will follow programming procedures, setting the amplitude 
according to the subject’s 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 may be felt at the sole of the foot and in the 
toes).   
 
3-4-10 Post Activation Follow-up Procedure 
Subjects will be followed up in visits at 12- and 24-weeks post-activation, with the 
primary analysis at 12 weeks. Participants from New Zealand will have one additional 
follow-up visit 3-years post-activation. 
1) At least 3 days prior to each appointment, subjects will be responsible to 
complete a 3-day voiding diary to be brought with them to each appointment. 
2) Assessments at visits 12 and 24-weeks, and 3-years post-activation contain the 
same procedures. They are described in the Visit Overview Section 3-4-2.  
At the follow-up visit 12 weeks post-activation, the primary effectiveness endpoint will 
have been reached. 
 
3-4-11 Explantation Procedure 
Subjects are intended to have their study device explanted between 2.5- and 3-years 
post-activation. This is so that subjects may continue to benefit from the therapy the 
device provides for the duration of the expected battery life, while still being covered by 
the Sponsor for device explantation. If the subject chooses not to have the device 
explanted by the 3-year post-activation date, they understand that they will not be 
covered by the Sponsor for a future explantation procedure. 
The explantation procedure is conducted as an outpatient procedure under local 
anesthesia for subcutaneous eCoin device removal. An incision site healing check will be 
performed 2 weeks post explantation. 
 Study Objectives 
3-5-1 Primary and Key Secondary Objectives 
3-5-1-1 Primary Effectiveness Objective 
To assess the effectiveness of eCoinTM on the proportion of subjects achieving at least a 
50% improvement in the number of urgency urinary incontinence episodes per 24 hours 
on a 3-day voiding diary after 12 weeks of therapy. 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
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3-5-1-2 Key Secondary Effectiveness Objective 
To assess the effectiveness of eCoinTM on the proportion of subjects achieving at least a 
50% improvement in the number of urgency urinary incontinence episodes per 24 hours 
on a 3-day voiding diary after 24 weeks of therapy. 
 
3-5-1-3 Primary Safety Objective 
To assess safety 16 weeks after reimplantation of eCoinTM. 
 
3-5-1-4 Key Secondary Safety Objective 
To assess safety 28 weeks after reimplantation of eCoinTM. 
 
3-5-2 Secondary Objectives 
The following objectives refer to measures taken after 12 and 24 weeks of therapy. 
 
To assess the proportion of subjects achieving 75% improvement in the number of 
urgency urinary incontinence episodes per 24 hours on a 3-day voiding diary. 
 
To assess the proportion of subjects achieving 100% improvement in urgency urinary 
incontinence episodes (“Dryness”) per 24 hours on a 3-day voiding diary. 
 
To assess the reduction in the number of urgency urinary incontinence episodes per 24 
hours on a 3-day voiding diary. 
 
To assess the reduction in the number of urinary voids per 24 hours on a 3-day voiding 
diary in those subjects whose baseline shows more than 10 voids per day. 
 
To assess the reduction in the number of urgency episodes per 24 hours on a 3-day 
voiding diary.  
 
To assess the reduction in the number of nocturia episodes per 24 hours on a 3-day 
voiding diary. 
 
To assess the improvement in the patient reported quality of life utilizing the 
Incontinence Quality of Life Questionnaire (IQoL). 
 
To assess the improvement in patient reported overactive bladder condition utilizing the 
Patient Global Impression of Improvement (PGI-I) questionnaire. 
 
To assess the patient reported satisfaction with eCoinTM therapy utilizing the custom 
patient satisfaction rating survey. 
 

 
Original Application for an Investigational Device Exemption 
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 Rationale for the Selection of Outcome Measures and Study 
Design 
eCoinTM therapy is expected to have a positive effect on a number of symptoms of 
overactive bladder, including number of urinary urgency incontinent episodes, 
frequency, and nocturia. The primary outcome is the therapeutic effect of eCoin on UUI.   
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). Thus, the primary outcome focuses on an objective and significant 
symptom of overactive bladder: the number of incontinence episodes in a 3-day period 
in all 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, patient reported questionnaires on 
the quality of life of incontinence patients have not been well standardized in the past.   
Selection of the two questionnaires is based on evidence that each, the IQoL and the 
PGI-I, is a valid and reproducible self-administered measure for assessing quality of life 
in patients with urinary incontinence (32, 33).  
 
The Sponsor’s feasibility study for which the study device, eCoinTM, was implanted in 46 
subjects showed a benign safety profile.  In particular, no infection at the implant site 
occurred that required explant.  At the time of this writing, all subjects have been 
followed for at least six months since implantation of the study device.  Given that the 
primary safety concern is infection and that all serious infections are expected to occur 
by one month after implantation, the adverse event information compiled thus far is 
promising.  Three serious adverse events (SAEs) have occurred: one unrelated 
pneumonia incident, one unrelated limp due to underlying bursitis of the hip present at 
screening, and one related cellulitis of the calf secondary to the ankle support suggested 
as post-operative care.  See Attachment 04-32 for additional information on safety. 
Furthermore, given the expected therapeutic similarity of percutaneous nerve stimulation 
of the tibial nerve to eCoinTM stimulation of the tibial nerve, the therapy is not expected to 
cause adverse events. Nonetheless, safety will be reported through adverse event 
reporting for the study duration.  
While an important benefit to the eCoinTM system is that delivery of therapy 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 all follow-up visits. 
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. 
 

 
Original Application for an Investigational Device Exemption 
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 Risk Analysis 
3-7-1 Overview 
The eCoinTM 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 that could result in patient harm, with action taken to reduce risk 
when the estimated risk for any potential hazard exceeds an acceptable level. The risk 
analysis for the eCoinTM system and the controller was performed early in the design 
process and has been updated throughout the process. The identified, anticipated risks 
have been mitigated so that all potential hazards are reduced to an acceptable severity 
and occurrence.   
To verify mitigation of risk, the eCoinTM 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 summarized 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 eCoinTM 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 and in a 
human feasibility trial for the treatment of overactive bladder (OAB) in adults.  The 
system parameters for the hypertension study were 2 pulses per second at a pulse width 
of 0.5 ms with amplitudes ranging from 0.5 mA to 25 mA. No adverse event related to 
stimulation therapy occurred during the two-year hypertension study. Section 2-2-2-2 is 
a summary of the safety results.  In this proposed study and in the ongoing OAB study, 
the eCoinTM 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.  In the OAB study, one adverse event 
related to stimulation occurred for which the subject experienced moderate pain during 
the intermittent stimulation (i.e., 30 minutes every other day).  This was the first subject 
programmed with the device in the U.S. and it was learned that the subject required 
more time for healing in order to provide better sensory feedback and to set the device 
to the upper level of comfort.  The adverse event was resolved with a reprogramming.  
The proposed system parameters match those utilized by many percutaneous tibial 
nerve stimulation studies for which no stimulation-related adverse event has been 
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 and 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 eCoinTM system is indicated for the treatment of patients having UUI.  For this 
follow-on study, subjects who received a study device in the feasibility study may be 
included. For inclusion, subjects must meet all inclusion criteria and none of the 
exclusion criteria. For more information about inclusion criteria, see Inclusion Criteria 3-
3-2-2-1. 
Patients with overactive bladder, including those with the symptom of urgency urinary 
incontinence, have a clinically and statistically significant lower quality of life, lower 
depression status, and poorer quality of sleep than other people (35).  Overactive 
bladder 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 investigating 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. Refractory patients may be eligible 
for inclusion in this study. 
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. 

 
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3-7-3 Justification for Investigation 
3-7-3-1 Potential Benefits of Treatment 
According to the American Urological Association (AUA) and its guideline for diagnosis 
and treatment of overactive bladder, an AUA 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 some features of 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 eCoinTM include improvements to the number of incontinence episodes, 
voiding volume, frequency, and quality of life.   
This current study is primarily concerned with UUI.   
3-7-4 Additional Safety Profile Information 
3-7-4-1 Description of Procedure  
eCoinTM 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 eCoinTM sits above the fascia so the deeper structures are not affected. No 
significant nerves or vessels, other than subcutaneous veins which are of minimal 
significance, are present in the subcutaneous pocket.  eCoinTM 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 
eCoinTM 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 complication from tibial nerve stimulation is known or anticipated.  
Stimulation pulses are charge balanced 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 
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 made only in the clinic where the 
patient response can be monitored and adjustments made as needed. 
The energy discharge of the eCoinTM battery is such that no harm will arise from heating 
due to a battery short. Direct shorting of the 75mAh 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. 

 
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3-7-4-3 Risks of eCoinTM Implantation 
The most probable risks associated with eCoinTM implantation include the following: 
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 that 
are categorized as uncommon or rare are reported below: 
UNCOMMON  
• 
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  
• 
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 
Device-related risks of the eCoinTM 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 or migration).  For the leadless eCoinTM system, lead-
related problems are not relevant.  Reasonable estimation of the rate of infection can be 
based upon other neuromodulation devices, the sponsor’s feasibility study testing 
eCoinTM for hypertension, and the sponsor’s feasibility study testing eCoinTM for OAB.  
Infection can be mitigated through surgical training, adequate manufacturing controls, 
and adequate after-care instructions.  Infection can be resolved through antibiotics 
generally and, in a worst-case scenario, explantation of eCoinTM. 
If needed, explantation of the eCoinTM 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 ongoing clinical study of eCoinTM for OAB conducted under an IDE, no patient 
required explant due to infection.  One cellulitis of the calf secondary to the ankle wrap 
occurred where the patient chose to have the device explanted prior to activation of the 
device. The aforementioned safety data are current as of the date of this writing at which 
time all patients have been followed at least six months from implantation. See 
Attachment 04-28 for a table on reported related adverse events.  In the OUS clinical 
study of eCoinTM for hypertension, the proportion of infection requiring explant, on a per 
patient basis was approximately 4.2%. See Subsection 2-2-2-1 and 2-2-2-2 for details on 
the adverse events that occurred during both studies. 

 
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The eCoinTM 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 eCoinTM 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 eCoinTM system is an active implantable device for long term patient contact 
duration (>30 days).  The eCoinTM 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 eCoinTM 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 
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 

 
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Standard 
Title 
Result 
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 eCoinTM device has 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 eCoinTM therapy for urgency urinary 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 eCoinTM implant, the same parameters as 
previously demonstrated in animal, in human studies, and in the eCoinTM for OAB 
feasibility trial 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 2 to 4 years before the 
device requires replacement.   
3-8-1 Components 
1) eCoinTM Implant – The implant is a coin-sized leadless battery powered device 23 
mm in diameter and 3.2 mm thick. The electronics and battery are hermetically 
enclosed 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. 
 

 
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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:3 days for the first 18 weeks and every 4 days thereafter (fixed)  
3-8-3 Implant Procedure 
Subcutaneous implantation of the eCoinTM 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 eCoinTM. Then, the eCoinTM is 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 eCoinTM System  
After a 4-week period of reimplant healing, the eCoinTM devices are activated with the 
stimulation amplitude set to the subject’s upper most comfortable level.  Once activated, 
the eCoinTM applies a 30-minute session of neuromodulation therapy at the programmed 
amplitude every 3 days for an 18-week period and then every 4 days thereafter.  All 
subjects are activated and the schedule of therapeutic sessions is automated as 
discussed. 
3-8-5 Subject Compliance Monitoring  
eCoinTM 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 and secondary endpoints.   
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. 

 
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3-8-6 Safety and Adverse Events  
3-8-6-1 Medical Monitoring  
The study will be approved by a study-wide independent ethical committee or 
institutional review board. The participating Investigators will monitor the subjects 
medically. 
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 
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 adverse event related to the 
device or placement procedure. 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, tibial 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. 

 
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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 as shown in 
Attachment 4-9, which are used at each visit. Unexpected or unrelated AEs or any 
requiring medical attention will be reported 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 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 a 
requirement to report expeditiously to regulators, IRBs, or both. 
 
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 
that 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 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 all 
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.  

 
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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. 
 
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 throughout the entire study 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, the AE 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 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 
This section describes reasons for withdrawal of subjects and termination of the study. A 
Statistical Analysis Plan (SAP) will describe in detail the methods for handling data from 
subjects who withdraw, or are withdrawn, early from the study. 
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 the subject is withdrawn. 
3-8-7-2 Terminating Subject Participation 
A subject’s continued participation in the study must be terminated if in the Investigator’s 
opinion, continued participation would be detrimental to the subject’s well-being.  If the 
subject is unwilling or unable to attend all remaining follow-up visits, or if subject is lost to 
follow-up, the subject’s continued participation must be terminated.  If the subject is 
explanted for any reason, subject participation must be terminated.   
The subject’s eCoinTM system must be recommended to be explanted if the subject’s 
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.  

 
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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 
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 eCoinTM system will be arranged. 
3-8-7-5 Data Collection and Follow-up for Withdrawn Subjects  
Subjects who are not implanted with the eCoin study device will not be followed after 
termination 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 quarterly report of Adverse Events. This DSMB will meet by telephone monthly until all 
subjects reach one-month post-implantation and at least quarterly until all subjects reach 
28 weeks post-reimplantation to review aggregate and individual subject data related to 
safety, data integrity, and overall conduct of the trial.  The DSMB will be responsible for 
reviewing adverse events.  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.   
CRFs for the study include: 
1) Screening  
2) Reimplantation (Part 1 and Part 2) 
3) Reimplant Healing Check 
4) eCoinTM Programming  
5) Follow-up (12 and 24 weeks post-activation) (And 3-year post-activation for NZ)  
6) Adverse Event 
7) Study Termination 
8) Protocol Deviation 
9) Explantation 
10) Explantation Healing Check 
11) Unplanned Visit 
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, and general study procedures. The monitor will also discuss any 
problems with the Investigator. Monitors will audit data collected on CRFs and verify 
data 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 each participant. 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 to collect all outstanding study data documents, ensure that the Investigator's 

 
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files are accurate and complete, review record retention requirements with the 
Investigator, make a final accounting of all study supplies 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 prospective, multicenter, single-arm follow-on study is designed to assess the 
safety and effectiveness of reimplantation of the eCoinTM tibial nerve 
neuromodulation system for the treatment of urgency urinary incontinence. A total of 
30 subjects from approximately 20 different centers will be enrolled. 
The remainder of this section briefly describes the analyses planned for this study. A full 
Statistical Analysis Plan (SAP) will be prepared. The SAP will include more technical 
and detailed elaboration of the statistical analyses. If there are minor differences 
between the analyses described in this section and the analyses in the SAP, the 
analyses in the SAP will prevail. A change to the data analysis methods described in the 
protocol will require a protocol amendment only if it alters a principal feature of the 
protocol. 
3-9-3-1 Rationale for Design Choice 
 Safety 
The feasibility trial of eCoinTM treating OAB with UUI in the US and New Zealand was 
conducted at 7 centers with 46 subjects implanted.  The results described in Section 2-2-
2-2 show a minimally invasive procedure under local anesthesia and minor wound 
healing problems.   
 
Under this protocol, eCoinTM will be tested to confirm the safety of the reimplantation 
procedure and the effectiveness of the replacement study device.  
 
 Effectiveness 
This open label, single-arm follow-on study will evaluate eCoinTM’s effectiveness in 
reducing episodes of urgency urinary incontinence. The proportion of subjects achieving 
at least a 50% reduction from baseline in the number of urgency urinary incontinence 
episodes will be reported.  
 

 
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3-9-3-2 Analysis Sets 
Effectiveness analyses will be generated for the ITT, mITT, OAB drug-free, PP, 
Responder, and TENS Cohort analysis sets. Adverse events will be reported on all 
subjects implanted through 12 weeks and 24 weeks post-activation. 
1) Intent-to-Treat (ITT): All enrolled subjects meeting the inclusion criteria of the 
study who are not ineligible because of exclusion criteria.  This is the primary 
analysis population for the effectiveness and safety analyses 
2) Modified Intent-to-Treat (mITT). All subjects in the ITT population who received 
an implant.  
3) OAB drug-free. All subjects in the mITT population who took no medication for 
OAB during the study period. 
4) Per-protocol (PP): The subset of OAB drug-free subjects excluding all subjects 
with any other major protocol violation. The SAP will define major protocol 
deviations. 
5) Responders: Subjects who respond to treatment, defined as those who achieve 
at least a 50% reduction in the number of urgency urinary incontinence episodes 
from baseline. 
 
The SAP may define additional analysis sets of subjects. 
 
3-9-3-3 Planned analyses 
 Primary Effectiveness Outcome 
 
The primary effectiveness outcome is achieving at least a 50% reduction from baseline 
in the number of urgency urinary incontinence episodes per 24 hours on a 3-day voiding 
diary after 12 weeks of eCoinTM tibial nerve stimulation.   
 
The proportion of responders along with its 2-sided 95% exact Clopper-Pearson 
confidence interval will be summarized after 12 weeks of therapy.  
 
 Key Secondary Effectiveness Outcome 
 
The key secondary effectiveness outcome is achieving at least a 50% reduction from 
baseline in the number of urgency urinary incontinence episodes per 24 hours on a 3-
day voiding diary after 24 weeks of eCoinTM tibial nerve stimulation. 
 
The proportion of responders along with its 2-sided 95% exact Clopper-Pearson 
confidence interval will be summarized after 24 weeks of therapy. 
 
 
 

 
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 Primary Safety Outcome 
 
The primary safety outcome is device-related adverse events from implantation to 16 
weeks after reimplantation of eCoinTM. 
 
All device-related adverse events up to 16 weeks after reimplantation of eCoinTM will be 
summarized by preferred term. Tabulations of these data will include the number of 
subjects exposed and the number of subjects with at least one device-related adverse 
event. 
 
 Key Secondary Safety Outcome 
 
The key secondary safety outcome is device-related adverse events 28 weeks after 
reimplantation of eCoinTM. 
 
All device-related adverse events up to 28 weeks after reimplantation of eCoinTM will be 
summarized by preferred term. Tabulations of these data will include the number of 
subjects exposed and the number of subjects with at least one device-related adverse 
event. 
 
This outcome will be formally tested statistically if the primary outcome is statistically 
significant. 
 Secondary Outcomes 
 
The secondary outcomes listed in this section are based on data after 12 and 24 weeks 
from activation (16 and 28 weeks after reimplantation). These outcomes, which for 
descriptive purposes, will not be formally analyzed statistically. The SAP will describe in 
detail analyses of the secondary outcomes. 
 
• 
Achieving 75% improvement in the number of urgency urinary incontinence 
episodes per 24 hours on a 3-day voiding diary. 
 
• 
Achieving 100% improvement in urgency urinary incontinence episodes 
(“Dryness”) per 24 hours on a 3-day voiding diary. 
 
• 
Reduction from baseline in the number of urgency urinary incontinence episodes 
per 24 hours on a 3-day voiding diary. 
 
• 
Reduction from baseline in the number of urinary voids per 24 hours on a 3-day 
voiding diary in those subjects whose baseline shows more than 10 voids per 
day. 
 
• 
Reduction from baseline in the number of urgency episodes per 24 hours on a 3-
day voiding diary.  
 
• 
Reduction from baseline in the number of nocturia episodes per 24 hours on a 3-
day voiding diary. 

 
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• 
Change from baseline in patient-reported quality of life utilizing the Overactive 
Bladder Symptom Quality of Life Questionnaire (IQoL). 
 
• 
Change from baseline in patient-reported overactive bladder condition utilizing 
the Patient Global Impression of Improvement (PGI-I) questionnaire. 
 
• 
Patient-reported satisfaction with eCoinTM therapy utilizing the custom patient 
satisfaction rating survey. 
 
3-9-3-4 Exploratory Subgroup Analyses 
Subjects who respond to treatment (i.e., who achieve at least a 50% reduction from 
baseline to 16 weeks post-reimplantation in the number of urgency urinary incontinence 
episodes per 24 hours on a 3-day voiding diary) will be compared to non-responders in 
terms of baseline characteristics, demographics, and effectiveness endpoints. 
 
3-9-4 Sample Size Consideration  
The follow-on study is designed to assess the proportion of subjects achieving a 
clinically meaningful level of improvement, defined as subjects with at least a 50% 
reduction from baseline in the number of urgency urinary incontinence episodes. A total 
of 30 subjects will be enrolled. See section 3-9-6 for details on handling primary outcome 
data for subjects who do not reach 12 weeks post-activation on study. 
 
3-9-5 Calculation of Effectiveness Variables 
Change in Urgency Urinary Incontinent Episodes:  Urgency Urinary Incontinent 
episodes (UUI) are measured prospectively using 3-day voiding diaries administered at 
12- and 24-weeks post-activation of the eCoinTM system, and will be compared to 
baseline measurements obtained from the Feasibility Study for Urgency Urinary 
Incontinence. 
Change in Frequency:  Frequency of urination is measured prospectively using 3-day 
voiding diaries administered at 12- and 24-weeks post-activation of the eCoinTM system, 
and will be compared to baseline measurements obtained from the Feasibility Study for 
Urgency Urinary Incontinence. 
Change in Quality of Life:  Quality of life is measured prospectively using the IQoL 
questionnaires administered at 12- and 24-weeks post-activation of the eCoinTM system, 
and will be compared to baseline measurements obtained from the Feasibility Study for 
Urgency Urinary Incontinence. 
Patient Global Impression of Improvement: The level of patient satisfaction with the 
eCoinTM 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 eCoinTM 
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. 

 
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3-9-6 Missing Outcome Data 
Because this study is investigating an implanted device, nearly all implanted patients are 
expected to have data on the primary and secondary endpoints.  Careful clinical 
planning that minimizes patient dropouts will be implemented.  
 
For the primary effectiveness outcome variable, missing data will be handled as follows: 
 
• 
Any subject explanted, except for those explanted for MRI, prior to 16 weeks 
post-reimplantation will be imputed as a non-responder (meaning the subject will 
be imputed as having not achieved at least a 50% reduction from baseline in the 
number of urgency urinary incontinence episodes). 
• 
Subjects who are explanted for MRI will have data post-MRI imputed. These 
imputed data for the primary effectiveness outcome variable will be assumed 
missing at random and will be handled with multiple imputation.  
• 
Any subject for whom 16-week post-reimplantation data are unavailable and the 
study investigator does not know whether the device has been explanted will be 
assumed to be a non-responder.  
• 
Subjects for whom 16-week post-reimplantation data are unavailable but the 
device is known not to have been explanted will have their missing data imputed. 
The missing data for the primary effectiveness outcome variable will be assumed 
missing at random and will be handled with multiple imputation.  
• 
Any subject who is enrolled, meets all inclusion and no exclusion criteria, but 
does not get implanted with eCoinTM will be imputed as a non-responder. 
Any subject who is enrolled, meets all inclusion and no exclusion criteria, but is later found 
to be ineligible prior to reimplantation will not be counted in the analyses. 
The SAP will contain details concerning model for multiple imputation. 
For the analysis of safety variables, only partial dates may be imputed; otherwise, 
missing data will be treated simply as missing. Conventions for imputing partial dates will 
be described in the SAP. 
 
The SAP will provide further details on handling missing data for the secondary 
outcomes, as well as details on sensitivity analyses on handling missing data for the 
primary effectiveness outcome. 
 
3-9-7 Additional OAB medications 
Subjects are not required to remain free or be washed off of pharmacological medications 
for overactive bladder. As this trial is a follow on to the feasibility study, it is unlikely that 
any individual will be taking pharmacological medications for OAB, but if they are, such 
information will be recorded.  
 

 
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Additional sensitivity analyses will be performed for the primary effectiveness outcome 
variable where subjects who have taken OAB medications will be imputed. The SAP will 
provide further details on the imputations. 
 
3-9-8 Safety Analysis 
All AEs will be coded using the preferred terms described in Subsection 3-7-4 Additional 
Safety Profile Information. All AEs will be summarized by preferred term. Tabulations of 
general AEs, which will be provided by time point, 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. These tabulations will be repeated for all AEs 
recorded as having a causal relationship to the eCoinTM system. Tabulations of local AEs 
will be provided at 12 and 24 weeks after activation (16 and 28 weeks after 
implantation), 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 
and other documents submitted to the Sponsor. Subjects should be identified by their 
subject study number only for documents submitted to the Sponsor.  Documents that are 
not for submission to the Sponsor, such as the signed informed consent forms, will only 
be viewed by an on-site monitor.  In compliance with ICH GCP Guidelines, the 
Investigator and institution are required to permit authorized representatives of the 
company, of any relevant regulatory agency, 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 site’s 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 their surgical designees 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 

 
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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 
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.  The device box will have 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 the other 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 maintain 
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 may 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, the event is 
considered non-compliance if it occurs without prior approval.  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.  Such failure could be grounds for physician 
disqualification. 
Use of a medication for OAB is not considered a major protocol deviation. 
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. Minor deviations from the protocol 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 follow: 
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 
Use of a medication for OAB is not considered a protocol deviation. 
3-10-6-3 Analyzing Deviations 
At each monitoring visit, the deviations log will be reviewed along with any additional 
deviations that might be discovered during the monitoring visit.  If any minor deviation is 
deemed to have an impact on the trial outcomes, the 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 applicable regulatory requirements. The Investigator will assure that 
no deviation from, or change to, the protocol will take place without prior agreement from 

 
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the Sponsor and documented approval from the IRB/Ethics Committee, except where 
necessary to eliminate an immediate hazard 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. 
 
 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: Stacy Chambliss, Chief of Administration  
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 eCoinTM 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 eCoinTM Subcutaneous Neuromodulation System described 
in section 3-8 are in attachment 4-19. Materials used outside of the hermetic package in 
the eCoinTM device are in attachment 4-20.  
Design inputs for the eCoinTM 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 eCoinTM 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 eCoinTM 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.  Subsequent to this trial and more relevant to 
the protocol described herein, the clinical use of eCoinTM in the treatment of OAB with 
urge urinary incontinence has been validated in a feasibility trial and the protocol is 
attached as Attachment 4-33. 
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 eCoinTM device is 
produced in accordance with the design and performance specifications (attachment 4-

 
Original Application for an Investigational Device Exemption 
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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. 
Study Sites and Investigators  
3-11-2 Organization and Participating Center 
3-11-2-1 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 20 investigators and centers.  
Sponsor 
Valencia Technologies Corporation 
Stacy Chambliss, Tel: +1 (661)775-1414 ext. 1002 
28464 Westinghouse Place 
Valencia CA, 91355 
United States 
3-11-3 Funding Source and Conflicts of Interest 
The study is funded by Valencia Technologies. Participating centers will be paid 
according to clinical trial agreements.  Participating physicians have disclosed their 
financial relationship in the Conflict of Interest statement incorporated within the signed 
Investigator Agreement,  
3-11-4 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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3-11-5 Roles and Responsibilities 
3-11-5-1 Investigator 
The Investigator has the following responsibilities: 
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 known risks and potential benefits associated with use of 
the device, and obtain the patient’s written consent for its use. 
6) Enroll subjects, execute study, and transcribe data from source documents to 
Case Report Forms. 
7) Submit annual progress reports, final reports, and adverse event reports to the 
IRB/Ethics Committee and to the 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 
authorized by the Sponsor. 
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. 
3-11-5-2 IRB/Ethics Committee 
The following are the responsibilities of the IRB: 
1) Review and approve, modify, or disapprove the study protocol and informed 
consent form. 
2) Receive continuing and final reports on study progress. 
3-11-5-3 Sponsor 
The Sponsor has the following responsibilities: 
1) Submit protocol and informed consent to IRB/Ethics Committee and FDA and 
await approval before starting the study. 
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 each Investigator. 
7) Control shipment of devices and surgical tools. 
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. 

 
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3-11-5-4 DSMB  
1) The responsibilities of the DSMB are outlined in the DSMB Charter (see 
Attachment 4-10).  
3-11-6 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 March 2019. Study enrollment of up to 30 subjects is 
expected to be completed by June 2019. All U.S. subjects are expected to complete the 
study by April 2020. New Zealand subjects are expected to complete the study by June 
2022. Monitoring is expected to be completed by August 2022. 

 
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4 Attachments  
 
 

 
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 3-day Voiding Diary 
 
 

 
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 Manuals, and Labels (refer to IDE G170301 Attachment 4-2) 
 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 63 of 93 
 Investigator’s Brochure (Not Applicable!) 
 
 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 64 of 93 
 Patient Trial Brochure and Advertisement (Not Applicable!) 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 65 of 93 
 Informed Consent Document 
 
 
 
 
 
 
 
 
 
 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 66 of 93 
 Patient Global Impression of Improvement (refer to IDE 
G170028 Attachment 4-6) 
 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 67 of 93 
 Patient Implantation Card (refer to IDE G170028 Attachment 
4-7) 
 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 68 of 93 
 Case Report Forms 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 69 of 93 
 Adverse Event Form 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 70 of 93 
 DSMB Charter (refer to IDE G170028 Attachment 4-10) 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 71 of 93 
 OUS Study for Hypertension Protocol (refer to IDE G170028 
or G170301 Attachment 4-11) 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 72 of 93 
 OUS Study for Hypertension CRFs for Infections (refer to 
IDE G170028 or G170301 Attachment 4-12) 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 73 of 93 
 OUS Study for Hypertension DSMB Letter Recommending 
Suspension of Implantation at Site 12 (refer to IDE G170028 
or G170301 Attachment 4-13) 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 74 of 93 
 SNS Risk Assessment (110-1493) (refer to IDE G170028 
Attachment 4-14) 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 75 of 93 
 Summary of Risks and Mitigations (refer to IDE G170028 
Attachment 4-15) 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 76 of 93 
 Design Verification and Validation Reports (refer to IDE 
G170301 Attachment 4-16) 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 77 of 93 
 Ethylene Oxide Sterilization Validation Reports (refer to IDE 
G170301 Attachment 4-17) 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 78 of 93 
 Sterile Packaging Validation Report (refer to IDE G170028 
Attachment 4-18) 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 79 of 93 
 Engineering Drawings (refer to IDE G170301 Attachment 4-
19) 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 80 of 93 
 eCoinTM Device Materials (refer to IDE G170028 Attachment 
4-20) 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 81 of 93 
 Template Investigator Agreement (refer to IDE G170028 
Attachment 4-21) 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 82 of 93 
 Clinical Monitoring Plan (refer to IDE G170028 Attachment 4-
22) 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 83 of 93 
 Assembly Procedure eCoinTM Device (refer to IDE G170028 
Attachment 4-23) 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 84 of 93 
 Assembly Procedure Sterilization and Packaging (refer to 
IDE G170028 Attachment 4-24) 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 85 of 93 
 List of Investigators, CVs, and Centers (refer to IDE G170028 
Attachment 4-25 and one additional investigator as 
submitted in this application) 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 86 of 93 
 303-1122 Software Design Specification SNS (refer to IDE 
G170301 Attachment 4-26) 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 87 of 93 
 Biocompatibility Reports (refer to IDE G170301 Attachment 
4-27) 
 
 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 88 of 93 
 Bacterial Endotoxins Test Method (refer to IDE G170301 
Attachment 4-28) 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 89 of 93 
 Bioburden Levels and Raw Data (refer to IDE G170301 
Attachment 4-29) 
 
 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 90 of 93 
 Battery Receiving Inspection Instructions (refer to IDE 
G170301 Attachment 4-30) 
 
 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 91 of 93 
 References (refer to IDE G170028 Attachment 4-31) 
 
 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 92 of 93 
 eCoinTM for OAB Feasibility: Safety (refer to IDE G170028 
Attachment 4-32) 
4-32-1 Adverse Event Table (refer to IDE G170028 Attachment 4-32-1) 
4-32-2 Subject 01-10 One Month Follow-up Implant Site Picture (refer 
to IDE G170028 Attachment 4-32-2) 
4-32-3 Subject 07-17 AE report (refer to IDE G170028 Attachment 4-
32-3) 
 
 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 93 of 93 
 eCoinTM for OAB Feasibility Study Protocol (refer to IDE 
G170028) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
Original Application for an Investigational Device Exemption 
Subcutaneous Tibial Nerve Stimulation for Urgency Urinary Incontinence: A Follow-on 
Study 
 
Valencia Technologies Corporation          Doc. No. 111-3335    Rev 1.2                    
CONFIDENTIAL                                               Page 94 of 93 
 Aftercare Instructions