A Prospective, Multicenter, Registry of the Lutonix Drug Coated Balloon for Treatment of Femoropopliteal Arteries (LEVANT 2 Safety Registry)
Phase: NA
Conditions: Peripheral Artery Disease, Femoropopliteal Artery Occlusion, Femoropopliteal Stenosis
Sponsor: C. R. Bard

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A Prospective, Multicenter, Registry of the Lutonix Drug 
Coated Balloon for Treatment of 
Femoropopliteal Arteries 
 
 
LEVANT 2 Safety Registry 
Investigational Plan 
Version 1.0 
 
Sponsor: 
 
 
 
 
Investigational Device: Lutonix Drug Coated Balloon (Formerly 
Moxy Drug Coated Balloon) 
 
 
NCT number: 01790243 (Number added post-approval per CT.gov requirement)  
 
 
This study will be conducted in compliance with the protocol and all other applicable regulatory 
requirements including the archiving of essential documents. 
 
 
Confidential Information 
No use or disclosure of this document outside Lutonix, Inc. is permitted without prior written 
authorization from Lutonix. 

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PROTOCOL SIGNATURE PAGE 
The LEVANT 2 Safety Registry Trial Investigational Plan 
 
A Prospective, Multicenter, Registry of the Lutonix Drug Coated Balloon for Treatment of 
Femoropopliteal Arteries. 
 
I have read this protocol and agree to adhere to the requirements. I will provide copies of this 
protocol and all pertinent information to the study personnel under my supervision and my hospital 
Institutional Review Board/Ethics Committee. I will discuss this material with them and ensure 
they are fully informed regarding the investigational device and the conduct of the study according 
to ICH Good Clinical Practice (GCP), ISO 14155, Declaration of Helsinki 21CFR 50, 56 and 812, 
and any local regulations. 
 
 
 
 
 
Clinical Site Name  
 
 
 
 
 
 
Site Principal Investigator 
Site Principal Investigator 
Date 
(Print Name) 
(Signature) 
 
 
 
 
 
 
 
Received by Sponsor: 
 
 
Date 
 
 
Initials 

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The LEVANT 2 Safety Registry Summary 
Title 
A Prospective, Multicenter, Registry of the Lutonix Drug Coated Balloon for 
Treatment of Femoropopliteal Arteries (LEVANT 2 Safety Registry) 
Investigational 
Device 
Lutonix Drug Coated Balloon (Formerly Moxy Drug Coated Balloon) 
Study Design 
Prospective, Multicenter, Registry, Safety and Efficacy 
Overview 
The purpose of the LEVANT 2 Safety Registry is to collect additional safety 
and efficacy data on the Lutonix Drug Coated Balloon in a large population. 
The study will enroll a similar patient population and follow the same 
medication regimen, follow-up schedule, and definitions as the LEVANT 2 
Randomized protocol. 
After successful protocol-defined pre-dilatation, subjects that are determined 
not to require stenting based on the defined angiographic criteria will be treated 
with the Lutonix Drug Coated Balloon and followed for 5 years. Subjects that 
do not meet post-predilatation lesion criteria are excluded (and treated per 
standard practice) and followed for safety for 30 days. 
Purpose 
To collect additional safety and efficacy information on the Lutonix Drug 
Coated Balloon for treatment of stenosis or occlusion of the femoral and 
popliteal arteries. 
Objective 
To assess safety and efficacy of use of the Lutonix Drug Coated Balloon for 
treatment of stenosis of the femoropopliteal arteries in a large population of 
subjects. 
Treatment 
All subjects meeting protocol-defined post pre-dilatation criteria will be treated 
with the Lutonix Drug Coated Balloon. 
Enrollment 
Enrollment will occur at up to 12 US centers and excludes sites that are 
participating in the LEVANT 2 Randomized trial and the LEVANT 2 
Continued Access Registry study. 
Up to 975 combined subjects are expected to be enrolled between the LEVANT 
2 Safety Registry and the LEVANT 2 Continued Access Registry to ensure 
approximately 650 subjects treated with the Lutonix Drug Coated Balloon 
between the two studies. 
Subject 
Follow-Up 
Schedule 
Clinical: 6, 12, and 24 Months 
Duplex Ultrasound (DUS): 0-30 days, 6 months, 12 months, and 24 months 
Telephone: 1, 36, 48 and 60 Months 
Primary 
Endpoint 
Rate of unanticipated device- or drug- related adverse events over time through 
60 months 
Secondary 
Endpoints 
Safety 
• Composite of freedom from all-cause perioperative (≤30 day) death 
and freedom from the following at 1, 6, 12, 24, 36, 48, and 60 
months: index limb amputation, index limb re-intervention, and 

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index-limb-related death. 
• Freedom at 30 days from all-cause death, index limb amputation 
above the ankle and target vessel revascularization (TVR) (VIVA 
Safety Endpoint) 
The following endpoints will be assessed at 1, 6, 12, 24, 36, 48 and 60 
months: 
• Rate of unexpected device- or drug-related adverse events 
• All-cause death 
• Amputation (above the ankle)-Free Survival (AFS) 
• Target Vessel Revascularization (TVR) 
• Reintervention for treatment of thrombosis of the target vessel or 
embolization to its distal vasculature 
• Major vascular complications 
• Readmission for cardiovascular events 
Efficacy 
• Acute Device, Technical and Procedural success 
The following endpoints will be assessed at 6, 12 and 24 Months: 
• Primary and Secondary Patency. 
• Alternative Primary and Secondary Patency based on alternative 
definitions of DUS PSVR <2.0 and <3.0 
• DUS Clinical Patency (DUS PSVR <2.5 without prior Clinically 
Driven TLR) 
• Target Lesion Revascularization (TLR) 
o Clinically-driven 
o 
Total (clinical and DUS/angiography-driven) 
• Change of Rutherford classification from baseline 
• Change of resting Ankle Brachial Index (ABI) from baseline 

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Inclusion 
Criteria 
Clinical Criteria 
1. 
Male or non-pregnant female ≥18 years of age; 
2. 
Rutherford Clinical Category 2-4; 
3. 
Patient is willing to provide informed consent, is geographically stable 
and comply with the required follow up visits, testing schedule and 
medication regimen; 
Angiographic Criteria 
Lesion Criteria 
4. 
Length ≤15 cm; 
5. 
Up to two focal lesions or segments within the designated 15 cm length 
of vessel may be treated (e.g. two discrete segments, separated by 
several cm, but both falling within a composite length of <15 cm); 
6. 
≥70% stenosis by visual estimate; 
7. 
Lesion location starts ≥1 cm below the common femoral bifurcation and 
terminates distally ≤2 cm below the tibial plateau AND ≥1 cm above 
the origin of the TP trunk; 
8. 
de novo lesion(s) or non-stented restenotic lesion(s) >90 days from prior 
angioplasty procedure; 
9. 
Lesion is located at least 3 cm from any stent, if target vessel was 
previously stented; 
10. Target vessel diameter between ≥4 and ≤6 mm and able to be treated 
with available device size matrix; 
11. Successful, uncomplicated (without use of a crossing device) antegrade 
wire crossing of lesion; 
12. A patent inflow artery free from significant lesion (≥50% stenosis) as 
confirmed by angiography (treatment of target lesion acceptable after 
successful treatment of inflow artery lesions); 
NOTE: Successful inflow artery treatment is defined as attainment of 
residual diameter stenosis ≤30% without death or major vascular 
complication. 
13. At least one patent native outflow artery to the ankle, free from 
significant (≥50%) stenosis as confirmed by angiography that has not 
previously been revascularized (treatment of outflow disease is NOT 
permitted during the index procedure); 
14. Contralateral limb lesion(s) cannot be treated within 2 weeks before 
and/or planned 30 days after the protocol treatment in order to avoid 
confounding complications; 
15. No other prior vascular interventions within 2 weeks before and/or 
planned 30 days after the protocol treatment. 

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Exclusion 
Criteria 
Patients will be excluded if ANY of the following conditions apply: 
1. 
Pregnant or planning on becoming pregnant or men intending to father 
children; 
2. 
Life expectancy of <5 years; 
3. 
Patient is currently participating in an investigational drug or other 
device study or previously enrolled in this study; 
NOTE: Enrollment in another clinical trial during the follow up period 
is not allowed. 
4. 
History of hemorrhagic stroke within 3 months; 
5. 
Previous or planned surgical or interventional procedure within 2 weeks 
before or within 30 days after the index procedure; 
6. 
History of MI, thrombolysis or angina within 2 weeks of enrollment; 
7. 
Rutherford Class 0, 1, 5 or 6; 
8. 
Renal failure or chronic kidney disease with MDRD GFR ≤30 ml/min 
per 1.73 m2 (or serum creatinine ≥2.5 mg/L within 30 days of index 
procedure or treated with dialysis); 
9. 
Prior vascular surgery of the index limb, with the exception of remote 
common femoral patch angioplasty separated by at least 2 cm from the 
target lesion; 
10. Inability to take required study medications or allergy to contrast that 
cannot be adequately managed with pre- and post-procedure medication; 
11. Anticipated use of IIb/IIIa inhibitor prior to randomization; 
12. Ipsilateral retrograde access; 
13. Composite lesion length is >15 cm or there is no normal proximal 
arterial segment in which duplex flow velocity can be measured; 
14. Significant inflow disease. Successful treatment of inflow disease 
allowed prior to target lesion treatment; 
15. Known inadequate distal outflow (>50 % stenosis of distal popliteal 
and/or all three tibial vessels), or planned future treatment of vascular 
disease distal to the target lesion; 
16. Sudden symptom onset, acute vessel occlusion, or acute or sub-acute 
thrombus in target vessel; 
17. Severe calcification that renders the lesion un-dilatable; 
18. Use of adjunctive treatment modalities (i.e. laser, atherectomy, 
cryoplasty, scoring/cutting balloon, etc.). 
Primary 
Analytical 
Subset 
All subjects treated with a DCB in the LEVANT 2 Randomized protocol, the 
LEVANT 2 Continued Access registry and the LEVANT 2 Safety Registry. 

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Principal 
Investigators 
Dr. Kenneth Rosenfield (USA) 
Prof. Dr. Dierk Scheinert (EU) 
Sponsor/ 
Contact: 
Lutonix, Inc. 
CRO 
Electronic Data 
Capture (EDC) 
Angiographic 
Core Lab 
DUS Core Lab 

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Table of Contents 
1 
INTRODUCTION ...................................................................................................................... 11 
1.1 
CLINICAL BACKGROUND ...................................................................................................... 11 
1.2 
DEVICE AND STUDY RATIONALE ........................................................................................ 15 
2 
STUDY OBJECTIVES AND ENDPOINTS ............................................................................ 15 
2.1 
PRIMARY OBJECTIVE .............................................................................................................. 16 
2.2 
PRIMARY ENDPOINTS ............................................................................................................. 16 
2.3 
SECONDARY ENDPOINTS ....................................................................................................... 16 
3 
DEVICE DESCRIPTION .......................................................................................................... 17 
3.1 
INTENDED USE / INDICATIONS FOR USE ........................................................................... 17 
3.2 
ACTIVE PHARMACEUTICAL INGREDIENT (API): PACLITAXEL .................................... 17 
3.3 
EXCIPIENT (Drug Carrier) ......................................................................................................... 18 
3.4 
DEVICE INSTRUCTIONS .......................................................................................................... 18 
3.5 
SUPPLY & SUPPORT OF INVESTIGATIONAL DEVICE ...................................................... 18 
4 
RISK-BENEFIT ANALYSIS .................................................................................................... 19 
4.1 
POTENTIAL RISKS .................................................................................................................... 19 
4.2 
RISK MANAGEMENT PROCEDURES .................................................................................... 21 
4.3 
POTENTIAL BENEFITS ............................................................................................................. 21 
4.4 
EARLY TERMINATION ............................................................................................................ 22 
5 
CLINICAL STUDY DESIGN ................................................................................................... 22 
5.1 
SCREENING PROCEDURES ..................................................................................................... 23 
5.2 
PATIENT SELECTION FOR ENROLLMENT .......................................................................... 24 
5.3 
SUBJECT INCLUSION AND EXCLUSION CRITERIA .......................................................... 25 
6 
STUDY/TREATMENT PROCEDURES ................................................................................. 27 
6.1 
ENROLLMENT ........................................................................................................................... 27 
6.2 
LUTONIX  DRUG COATED BALLOON INSTRUCTIONS FOR USE (IFU) ......................... 27 
6.3 
BASELINE ANGIOGRAM ......................................................................................................... 28 
6.4 
IN-FLOW LESION TREATMENT ............................................................................................. 28 
6.5 
PRE-DILATATION ..................................................................................................................... 28 
6.6 
TREATMENT .............................................................................................................................. 29 
6.7 
POST TREATMENT AND PROVISIONAL (BAILOUT) STENTING PROCEDURES.......... 29 
6.8 
UNSCHEDULED ANGIOGRAPHY/REVASCULARIZATION. .............................................. 30 
7 
TREATMENT OF SUBJECT ................................................................................................... 30 
7.1 
MEDICATIONS ........................................................................................................................... 30 
7.2 
STANDARD TESTS, PROCEDURES, AND FOLLOW-UP ..................................................... 32 

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8 
ADVERSE EVENTS .................................................................................................................. 34 
8.1 
ADVERSE EVENT REPORTING .............................................................................................. 34 
9 
SUBJECT WITHDRAWAL CRITERIA ................................................................................ 34 
10 
DATA COLLECTION AND MONITORING ........................................................................ 35 
10.1 
DATA COLLECTION ................................................................................................................. 35 
10.2 
MONITORING ............................................................................................................................ 35 
10.3 
SOURCE DOCUMENTATION .................................................................................................. 36 
10.4 
RECORD RETENTION............................................................................................................... 37 
10.5 
STUDY PROCESSING ............................................................................................................... 38 
11 
DEVICE ACCOUNTABILITY ................................................................................................ 38 
11.1 
SUPPLY AND SUPPORT OF INVESTIGATIONAL DEVICE ................................................ 39 
12 
STUDY MANAGEMENT ......................................................................................................... 39 
12.1 
STEERING COMMITTEE ......................................................................................................... 39 
12.2 
SAFETY COMMITTEES ............................................................. Error! Bookmark not defined. 
13 
REGULATORY RESPONSIBILITIES ................................................................................... 40 
13.1 
IRB/EC APPROVAL ................................................................................................................... 40 
13.2 
INFORMED CONSENT .............................................................................................................. 40 
13.3 
SELECTION OF CLINICAL SITES AND INVESTIGATORS ................................................. 40 
13.4 
INVESTIGATOR’S RESPONSIBILITIES ................................................................................. 41 
13.5 
LUTONIX RESPONSIBILITIES ................................................................................................ 42 
14 
PUBLICATIONS ....................................................................................................................... 43 
15 
STATISTICAL ANALYSIS PLAN .......................................................................................... 43 
15.1 
OVERVIEW OF STUDY DESIGN ............................................................................................. 43 
15.2 
SAMPLE SIZE JUSTIFICATION ............................................................................................... 44 
15.3 
ANALYSIS .................................................................................................................................. 44 
APPENDIX A:  DEFINITIONS ........................................................................................................ 45 
APPENDIX B:  DRAFT CASE REPORT FORM ELEMENTS .................................................... 53 
APPENDIX C:  SAMPLE INSTRUCTIONS FOR USE ................................................................. 67 
APPENDIX D: SAMPLE INFORMED CONSENT FORM .......................................................... 68 
APPENDIX E:  ANGIOGRAPHIC ACQUISITION GUIDELINES ............................................ 69 
APPENDIX F: DUPLEX ULTRASOUND CORE LAB GUIDELINES ....................................... 70 
 
Tables 
Table 1: THUNDER and FemPac Results ..................................................................................................... 13 
Table 2: Device Matrix, Lutoix Drug Coated Balloon................................................................................... 18 

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Table 3: Post Pre-Dilatation Lesion(s) Criteria .............................................................................................. 28 
Table 4: Provisional (Bailout) Criteria ........................................................................................................... 29 
Table 5: Medication Schedule........................................................................................................................ 31 
Table 6: Follow-Up Schedule and Testing Requirements for treated subjects .............................................. 32 
Table 7: Reports Required From Clinical Investigators ................................................................................ 42 
Figures 
Figure 1:  Lutonix Drug Coated Balloon ....................................................................................................... 17 
Figure 2 : Chemical Structure of Paclitaxel ................................................................................................... 18 
Figure 3: Study Flowchart ............................................................................................................................. 23 
Figure 4: Allowed Lesion Location ............................................................................................................... 25 

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1 INTRODUCTION 
The purpose of the LEVANT 2 Safety Registry is to collect additional safety and efficacy 
information on the Lutonix Drug Coated Balloon (formerly known as Moxy Drug Coated Balloon) 
for treatment of stenosis or occlusion of the femoropopliteal arteries in a larger patient population. 
Enrolled subjects will meet the same protocol requirements and undergo the same follow up and 
testing schedule as the LEVANT 2 Randomized protocol. 
1.1 CLINICAL BACKGROUND 
Peripheral arterial disease (PAD) is estimated to be present in 3% of people in the age range of 40- 
59 years and in 20% of people over 70 years1 of age. The femoropopliteal artery is the most 
commonly diseased artery in the peripheral circulation, and is the site of a larger percentage of 
lower limb interventions2. Because of the vessel’s unique characteristics, such as significant 
shortening, elongation, torsion, flexion, and vulnerability to external compression, superficial 
femoral artery (SFA) disease can be associated with severe and life threatening complications3 and 
a very high frequency of restenoses after percutaneous intervention4. The Lutonix Drug Coated 
Balloon may help reduce the rates of restenosis and the need for repeat endovascular or surgical 
procedures. 
Four decades after the first femoropopliteal angioplasty was performed with sequential dilators in 
19645, a durable endovascular treatment for femoropopliteal disease is yet to be identified. 
Percutaneous transluminal angioplasty (PTA) has become the most common therapy, but PTA is 
challenged by a high rate of restenosis and a frequent need for reintervention; the one year patency 
of PTA without reintervention is estimated to be only 33% in a recent meta-analysis6. Bare metal 
stents (BMS) were successful at preventing recoil and dissection, but stent outcomes in the 
femoropopliteal artery are complicated by stent fracture, and restenosis rates of BMS are as high as 
40-60% in the peripheral vasculature7. Restenosis is caused by neointimal hyperplasia, a 
hyperproliferative response to the vessel injury caused by angioplasty and the foreign body 
reaction and abnormal vessel geometry caused by stent implantation. In the coronary vasculature, 
 
 
1 Zeller, T. Current state of endovascular treatmet of femoro-popliteal artery disease. Vas Med 12 (2007): 223-234. 
2 Levy PJ. Epidemiology and pathology of peripheral arterial disease. Clin Cornerstone. 2002; 4(5):1–15. 
3 Murabito JM, et. al. Temporal trends in the incidence of intermittant claudication from 1950 to 1999. Am J of 
Epidemiol 2005;162:430-7) 
4 Smouse, HB, et. al. Biomechanical forces in the femoropopliteal arterial segment. Endovascular Today. 2005; June 
60. 
5 Dotter, CT. Transluminal recanalization and dilatation in atherosclerotic obstruction of femoral popliteal system. 
Am Surg 31 (1965): 453-59. 
6 Rocha-Singh, KJ, et. al. Performance Goals and Endpoint Assesssments for Clinical Trials of Femoropopliteal Bare 
Nitinol Stents in Patients with Symptomatic Peripheral Arterial Disease. Cath and Cardio Inter 69 (2007): 910. 
7 Dormandy JA, Rutherford RB. Management of peripheral arterial disease (peripheral arterial disease) TASC 
Working Group. TransAtlantic Inter-Society Consensus (TASC). J Vasc Surg 31 (2000): S1-S296. 

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this challenge has largely been mitigated in the last decade by the introduction of drug eluting 
stents (DES). However, in the peripheral vasculature DES have not proven as beneficial8, 
although a recent publically presented peripheral study investigating a paclitaxel coated stent has 
shown benefit over BMS9. 
The introduction of bare nitinol stents improved outcomes over PTA alone and early generation 
BMS showed a primary patency between 60 and 80% at one year. The recently published 
RESILIENT study10 tested a new, flexible nitinol stent and showed a primary patency rate of 
81.3% in the stent group vs. 36.7% in the PTA group. Provisional nitinol stent implantation has 
become the worldwide standard-of-care in the SFA in cases where PTA results are suboptimal 
(e.g. flow limiting dissection, severe recoil, or unacceptable residual stenosis). Provisional 
stenting is designated as a ‘class IIa’ recommendation per the most recent 2005 ACC/AHA 
guideline for management of peripheral artery disease11. 
Stent outcomes in the femoropopliteal artery are complicated by the vessel’s unique physiologic 
characteristics and possibility of stent fracture, and restenosis remains a clinical challenge. In 
addition, implantation of a stent can complicate and limit the treatment choices available to the 
patient in the event repeat intervention or surgery becomes necessary. 
A novel therapy that is commercially available in some countries and under investigation in others 
is the drug coated balloon (DCB), an otherwise standard PTA catheter with a drug coating on the 
balloon surface. During angioplasty, DCBs are designed to deliver an anti-proliferative drug 
directly to tissues of the treated vessel wall, thus inhibiting neointimal hyperplasia and restenosis 
without the need for a permanent foreign body implant. The investigational device of the present 
study, the Lutonix Drug Coated Balloon, is one example of a DCB. 
 
 
 
 
8 Duda, SH et. al. Drug-Eluting and Bare Nitinol Stents for the Treatment of Atherosclerotic Lesions in the Superficial 
Femoral Artery. J Endovasc Ther 13 (2006): 701. 
9 Dake M. The Zilver PTX Randomized Trial: 12 month Results of a Paclitaxel-Eluting Stent Versus Balloon 
Angioplasty and Bare Metal Stenting in Patients with Femoropopliteal Artery Disease Presentation at 2010 TCT. 
10 Laird, JR, Katzen BT et. al. Nitinol Stent Implantation Versus Balloon Angioplasty for Lesions in the Superficial 
Femoral Artery and Proximal Popliteal Artery: Twelve-Month Results From the RESILIENT Randomized Trial. Circ 
Cardiovasc Interv. 2010;3:267-276. 
11 Hirsch AT, Haskal ZJ, Hertzer NR, Bakal CW, Creager MA, Halperin JL, Hiratzka LF, Murphy WRC, Olin JW, 
Puschett JB, Rosenfield KA, Sacks D, Stanley JC, Taylor LM Jr., White CJ, White J, White RA. ACC/AHA 
guidelines for the management of patients with peripheral arterial disease (lower extremity, renal, mesenteric, and 
abdominal aortic): executive summary: a report of the American College of Cardiology/American Heart Association 
Task Force on Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With 
Peripheral Arterial Disease [Lower Extremity, Renal, Mesenteric, and Abdominal Aortic]). J Am Coll Cardiol. 
2006;47:1239–1312. 

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To date, two pilot European clinical trials for treatment of femoropopliteal arteries have been 
performed by another manufacturer to assess their drug coated balloons using the Paccocath® 
technology. The Paccocath coating contains the same active pharmaceutical ingredient (API) – 
paclitaxel - as in the Lutonix drug coating, but a different carrier (iopromide). This same API is 
currently used in some manufacturers’ approved drug eluting stents. Both studies have 
demonstrated preliminary safety and decreased restenosis of the femoropopliteal lesions in the 
context of standard-of-care stenting. Both the THUNDER12 and FemPac13 studies were 
prospective, randomized, controlled, multi-center clinical trials that compared the Paccocath 
coated DCB to control PTA with provisional stenting allowed in both arms. Subject characteristics 
were similar in both studies, however overall lesion lengths were notably shorter in the FemPac 
trial. In both studies, DCB-treated subjects had significantly less late lumen loss (the primary 
endpoint), less restenosis, and a lower rate of reintervention (target lesion revascularization (TLR)) 
at 6 months than those treated with control PTA. The potential benefit of DCB demonstrated by 
these pilot studies is tabulated in the Table 1. 
TABLE 1: THUNDER AND FEMPAC RESULTS 
THUNDER 
Endpoint 
DCB (n=48) 
PTA (n=54) 
Late Lumen Loss (6 month), n±SD 
- Primary Endpoint (p=0.001) 
0.4 ±1.2 
1.7 ±1.8 
Binary Restenosis (6 month) 
17% 
44% 
TLR (6 month) 
4% 
37% 
TLR (24 month) 
15% 
52% 
FemPac 
Endpoint 
DCB (n=41) 
PTA (n=48) 
Late Lumen Loss (6 month), n±SD 
- Primary Endpoint (p=0.031) 
0.5 ±1.1 
1.0 ±1.1 
Binary Restenosis (6 month) 
19% 
47% 
TLR (6 month) 
7% 
33% 
TLR (24 month) 
13% 
50% 
The results of these two early pilot studies suggest that local delivery of paclitaxel by a DCB 
directly to tissues of the diseased vessel wall is safe and effective as a treatment for 
femoropopliteal stenosis. 
 
 
 
 
 
12 Tepe G. et, al. Local Delivery of Paclitaxel to Inhibit Restenosis during Angioplasty of the Leg. NEJM. 2008, 
358;7. 689-699. 
13 Werk M et. al. Inhibition of Restenosis in Femoropopliteal Arteries. Circulation. 2008;118(13):1358-65. 

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1.1.1 
THE LEVANT I FIRST-IN-MAN TRIAL SUMMARY 
The LEVANT I trial (NCT00930813) is a trial which compared femoropopliteal treatment with the 
Lutonix Drug Coated Balloon to a standard PTA catheter (with and without stenting) with a 
primary endpoint of late lumen loss. One hundred-one randomized subjects have been enrolled at 9 
European centers. After a defined pre-dilatation, subjects were stratified to the balloon strata or 
stent strata and then randomized to treatment with the Lutonix DCB or a standard PTA catheter 
(control group). Subject inclusion and exclusion criteria were similar to previous femoropopliteal 
studies, with lesion length of 4-15 cm and vessel diameter 4-6 mm. Subject demographics, 
baseline lesion characteristics, Rutherford Category, device, and procedural success were similar 
between arms. 
In this randomized, controlled clinical study, the Lutonix DCB demonstrated significantly less late 
lumen loss at 6 months and similar safety through 24 months by direct comparison to conventional 
balloon angioplasty. The primary objective was met, and the angiographic and clinical results of 
the LEVANT I trial demonstrate the feasibility, safety, and efficacy of use of the Lutonix DCB for 
treatment of femoropopliteal lesions. 
 
In the ITT population, the primary endpoint of mean Late Lumen Loss at 6 months was better in 
the Lutonix DCB arm (0.46±1.13) compared to the POBA arm (1.09±1.07), with a p value of 
0.016, consistent with efficacy of the Lutonix DCB for this indication. The difference in mean late 
loss between arms was also lower in the balloon-only stratification group (0.45±1.18 vs. 
1.19±1.15, p=0.024). 
 
The Lutonix DCB demonstrated safety comparable to conventional angioplasty (POBA) in the LEVANT I 
Trial, with similar ITT AE and SAE rates through 24 months. There were no unanticipated adverse device 
effects in the drug-coated balloon arm, and overall adverse event rates were similar to conventional 
uncoated balloon angioplasty. The percentage of subjects with any death, amputation, or target lesion 
thrombosis was 8% for Lutonix DCB compared to 12% for control POBA at study completion. 
Secondary clinical endpoints trended in favor of the Lutonix DCB arm on an ITT basis through 
study completion at 24 months, including TLR (36% vs. 49%, p = 0.23), TVR (36% vs. 51%, p = 
0.15), and primary patency (54% vs. 32% for DUS PSVR < 2.5 without TLR, p = 0.05), which are 
clinically relevant findings consistent with safety of the experimental device and treatment effect 
over standard PTA. There was no evidence for diminished treatment effect over time; on the 
contrary, the difference in ITT primary patency between test and control increased after 2 years of 
follow-up. This was true even in the context of 8 (16%) Lutonix DCB subjects treated with 
malfunctioning devices that did not fully inflate because twisted balloon folds, and after 2 years all 
of these had failed primary patency. 
 
In the post hoc subset of subjects treated with normally functioning devices without geographic 
miss, Lutonix DCB had a lower TLR rate (19% vs. 55%, p = 0.006) and higher primary patency 

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(72% vs. 33% for DUS PSVR < 2.5 without TLR, p = 0.005) compared to uncoated PTA balloons. 
This observation suggests a durable treatment effect and supports the importance of the improved 
manufacturing processes (to ensure proper balloon folding) and physician training procedures (to 
minimize geographic miss) that have since been implemented. 
 
Two year clinical follow-up has been completed. Safety of the Lutonix DCB was indistinguishable 
(and trending superior to) control uncoated balloon angioplasty. The successful primary endpoint 
of late lumen loss at 6 months and higher primary patency at 2 years demonstrates efficacy. 
 
 
1.2 DEVICE AND STUDY RATIONALE 
The Lutonix Drug Coated Balloon is indicated for percutaneous transluminal angioplasty of 
obstructive de novo or non-stented restenotic lesions in native femoropopliteal arteries ≤15 cm in 
length and >4.0 to <6.0 mm in diameter. 
The drug coating on the Lutonix Drug Coated Balloon contains paclitaxel and excipients (drug 
carrier) with a history of human safety for intravenous use. Each component has been safely used 
in other products. PTA catheters have been in commercial use for over 25 years, and the Lutonix 
Drug Coated Balloon meets international standards (e.g. ISO 10555) developed over time to 
validate the mechanical safety of dilation catheters. The anti-proliferative drug paclitaxel is a well 
understood active pharmaceutical ingredient (API) with an extensive history of human use in 
oncology14 and drug-eluting stents (DES)15. The maximum total dose of 3.8 mg on the largest 
peripheral Lutonix Drug Coated Balloon is less than 2% of the dose of approximately 300mg 
infused during a single course of cancer therapy. In addition, GLP animal Safety and Safety 
Margin studies have been performed to confirm the safety of the Lutonix Drug Coated Balloon. 
 
 
2 STUDY OBJECTIVES AND ENDPOINTS 
Data from all subjects treated with DCB in the LEVANT 2 Randomized protocol (roll-in and 
randomized to DCB), the LEVANT 2 Continued Access Registry and the LEVANT 2 Safety 
Registry will be combined and analyzed descriptively. Secondary as-treated, unstented, and per- 
protocol analyses will also be performed. 
 
 
 
 
 
 
14 Pacific Yew: Draft Environmental Impact Statement. Appendices. U.S. Departments of Agriculture, Interior, and Health and 
Human Services. January 1993. 
15 Lasala J, et.al. An Overview of the TAXUS® Express®, Paclitaxel-Eluting Stent Clinical Trial Program. Journal of 
Interventional Cardiology. 2006, Vol 19: 5 pp431-442 

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2.1 PRIMARY OBJECTIVE 
The primary objective of the LEVANT 2 Safety Registry is to assess safety and efficacy of use of 
the Lutonix Drug Coated Balloon for treatment of stenosis of the femoropopliteal arteries in a large 
population of subjects. 
 
 
2.2 PRIMARY ENDPOINTS 
Rate of unanticipated device- or drug- related adverse events over time through 60 months. 
 
2.3 SECONDARY ENDPOINTS 
The following endpoints will be reported using descriptive statistics in the final Study Report. 
Safety 
• Composite of freedom from all-cause perioperative (≤ 30 day) death and freedom from 
the following at 1, 6, 12, 24, 36, 48, and 60 months: index limb amputation, index limb 
re-intervention, and index-limb-related death. 
• Freedom at 30 days from all-cause death, index limb amputation above the ankle and 
target vessel revascularization (TVR) (VIVA Safety Endpoint) 
The following endpoints will be assessed at 1, 6, 12, 24, 36, 48 and 60 months: 
• Rate of unanticipated device- or drug-related adverse events 
• All-cause death 
• Amputation (above the ankle)-Free Survival (AFS) 
• Target Vessel Revascularization (TVR) 
• Reintervention for treatment of thrombosis of the target vessel or embolization to its 
distal vasculature 
• Major vascular complications 
• Readmission for cardiovascular events 
 
Efficacy 
• Acute Device, Technical and Procedural success 
 
The following endpoints will be assessed at 6, 12 and 24 Months: 
• Primary and Secondary Patency. Primary Patency is defined as the absence of target 
lesion restenosis (defined by DUS peak systolic velocity ratio (PSVR) ≥ 2.5) and 
freedom from target lesion revascularization (TLR). 
• Alternative Primary and Secondary Patency based on alternative definitions of DUS 
PSVR < 2.0 and < 3.0 
• DUS Clinical Patency (DUS PSVR < 2.5 without prior Clinically Driven TLR) 
• Target Lesion Revascularization (TLR) 

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o Clinically-driven 
o Total (clinical and DUS/angiography-driven) 
• Change of Rutherford classification from baseline 
• Change of resting Ankle Brachial Index (ABI) from baseline 
3 DEVICE DESCRIPTION 
The Lutonix Drug Coated Balloon is a standard PTA catheter with a drug coating on the balloon 
portion of the catheter. The Lutonix Drug Coated Balloon is an over-the-wire type design with 
working lengths of 100 and 130 cm and is compatible with 0.035” guidewires. Marker bands are 
located at the proximal and distal ends of the balloons to assist in delivery and placement. The 
balloon surface between the marker bands is coated with a specialized immediate release non- 
polymer based coating formulation that includes the anti-proliferative drug – paclitaxel - at a 
surface concentration of 2μg/mm2. 
 
 
FIGURE 1: LUTONIX DRUG COATED BALLOON 
 
 
All devices are provided sterile and for single-use only and are clearly labeled for investigational 
use only. No more than two devices may be deployed in a single target lesion during a single 
procedure. 
3.1 INTENDED USE / INDICATIONS FOR USE 
The Lutonix Drug Coated Balloon is indicated for percutaneous transluminal angioplasty of 
obstructive de novo or non-stented restenotic lesions in native femoropopliteal arteries ≤15cm in 
length and >4.0 to <6.0mm in diameter. 
3.2 ACTIVE PHARMACEUTICAL INGREDIENT (API): PACLITAXEL 
Paclitaxel, discovered in 1967 and commercially developed by Bristol-Myers Squibb, is a well 
known mitotic inhibitor indicated for use in the treatment of patients with lung, ovarian, breast, 
head and neck cancers and advanced forms of Kaposi’s sarcoma. Paclitaxel is also approved for 
the prevention of restenosis. Various dosages are used depending on target treatment and range 
from multiple 300 mg IV infusions for oncology therapy to a single maximal nominal dose of 282 
µg for devices that treat restenosis, such as coronary stents. Please refer to Figure 2 and the 
Investigator’s Brochure for a more detailed review of paclitaxel. 

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FIGURE 2 : CHEMICAL STRUCTURE OF PACLITAXEL 
 
 
3.3 EXCIPIENT (DRUG CARRIER) 
The balloon coating includes small amounts of well known excipients (drug carrier) that are 
approved by the Food and Drug Administration (FDA) as inactive ingredients in drug products for 
intravenous (IV) drug delivery. 
3.4 DEVICE INSTRUCTIONS 
A comprehensive set of Instructions for Use (IFU), including warnings and precautions, has been 
created. Please refer to the most current IFU packaged with the device for complete details on 
preparation and procedural use of the device. A sample IFU can be found in Appendix C. 
3.5 SUPPLY & SUPPORT OF INVESTIGATIONAL DEVICE 
An investigational device supply of the Lutonix Drug Coated Balloon will be made available to all 
activated study sites. The investigational device matrix that is currently available for this study is 
listed in Table 2. Always confirm current site inventory supply prior to enrolling subjects into the 
study. 
TABLE 2: DEVICE MATRIX, LUTONIX DRUG COATED BALLOON 
Balloon 
Diameters 
Balloon Lengths 
40mm 
60 mm 
100 mm 
4 mm 
 
 
 
5 mm 
 
 
 
6 mm 
 
 
 
 
Prior to start of study enrollment, Lutonix or their designee will perform formal device training for 
study site personnel and support staff that have not been previously trained on the use of the 
Lutonix Drug Coated Balloon. Each study site will receive a supply of the Lutonix Drug Coated 
Balloons upon completion of the protocol requirements for study initiation. Additional training 
and support will be provided as needed on an ongoing basis. Any unused devices must be returned 
to the sponsor at the time site enrollment stops or upon sponsor request. After use, this product 
may be a potential biohazard. Handle and dispose of in accordance with acceptable medical 
practices and applicable local, state and federal laws and regulations. For quality control purposes, 

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devices may be requested to be returned to the sponsor before or after use, in which case the site 
should return devices by following the Return Material Authorization (RMA) instructions located 
in the study binder. 
4 RISK-BENEFIT ANALYSIS 
4.1 POTENTIAL RISKS 
The potential risks and benefits of participation in this study are clearly identified in the subject 
Informed Consent Form (ICF) and are to be explained to the subject and/or their legal 
representative prior to participating in the study. The Lutonix Drug Coated Balloon and standard 
uncoated percutaneous angioplasty catheters are intended to be the only devices used for treatment 
of the target lesion. 
Due to the high similarity of the Lutonix Drug Coated Balloon to other marketed balloon catheters, 
procedural use is not expected to significantly change or increase risks during the initial procedure. 
However, it shares the risks of conventional balloon angioplasty treatment of patients with 
femoropopliteal disease. There may also be risks associated with the drug coating on the Lutonix 
Drug Coated Balloon that are unknown at this time. Please refer to the Investigator’s Brochure for 
more details on the development of the Lutonix Drug Coated Balloon. 
4.1.1 
RISKS FOR PERIPHERAL CATHETERIZATION PROCEDURE 
Potential adverse events which may be associated with a peripheral balloon dilatation 
catheterization procedure include, but are not limited to, the following: 
• abnormal heart rhythms 
• abrupt vessel closure 
• allergic reaction 
• aneurysm or rupture of the artery 
• AV fistula 
• bleeding 
• death 
• dissection 
• embolization 
• femoral nerve compression with associated neuropathy 
• groin area bruising and discomfort 
• hematoma 
• infection 
• kidney failure 
• low blood pressure 
• perforation 
• pseudoaneurysm 
• respiratory failure 

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• stroke 
• total occlusion or thrombosis 
• vessel trauma that may require re-intervention or surgical repair 
There may be other potential adverse events that are unforeseen at this time. 
Even if the balloon catheter procedure is deemed successful, it is associated with a meaningful risk 
of vessel narrowing within 12 months (depending on risk factors). Additional therapy may be 
required within 12 months such as re-intervention using angioplasty or surgery. 
Patients undergoing an interventional procedure are often treated with courses of thienopyridines 
such as clopidogrel or prasugrel, which may cause thrombocytopenic purpura and/or bleeding 
complications. In rare cases, these drugs may cause a significant reduction in white blood cell 
count, which may in turn result in serious infections. Aspirin is also a common drug used before 
and after such procedures. Aspirin is known to contribute occasionally to causing gastrointestinal 
ulcers (bleeding or non-bleeding). Aspirin may also affect platelet function to the extent of 
causing bleeding complications (which may be minor, major, or life threatening). If such 
conditions occur, the patient may require surgery, blood transfusion, or platelet transfusion. 
Any of the above could cause prolonged illness, permanent impairment of daily function or, in rare 
cases, death. Possible treatments could include, but are not limited to emergency PTA and vascular 
surgery. It is expected that the fluoroscopy time of the interventional procedure will be similar to 
the time required for conventional percutaneous lower extremity interventional procedures and not 
pose additional risks to the subject or lab personnel. 
4.1.2 
ASSOCIATED RISKS FROM THE DRUG COATING 
The balloon coating includes the API paclitaxel and small amounts of well known excipients (drug 
carrier) that are approved by the Food and Drug Administration (FDA) as inactive ingredients in 
drug products for intravenous (IV) drug delivery. Additional adverse events that may be unique to 
the paclitaxel drug coating include: 
• allergic/immunologic reaction 
• alopecia 
• anemia 
• blood product transfusion 
• gastrointestinal symptoms 
• hematologic dyscrasia (including leukopenia, neutropenia, thrombocytopenia) 
• hepatic enzyme changes 
• histologic changes in vessel wall, including inflammation, cellular damage or necrosis 
• myalgia/arthralgia 
• peripheral neuropathy 

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There may be other risks associated with the drug coating that are unknown at this time. 
There are no adequate and well-controlled studies published in pregnant women or men intending 
to father children who have received paclitaxel in either the test or control device. Studies 
performed in rats and rabbits receiving IV paclitaxel during organogenesis revealed evidence of 
maternal toxicity, embryotoxicity, and fetotoxicity at dosages of 1 and 3 mg/kg, respectively 
(approximately 3 and 16 times the dose provided by the largest Lutonix Drug Coated Balloon- 
coated with 3.8 mg of paclitaxel adjusted for body surface area). The drug resulted in increased 
resorptions and increased fetal deaths. No teratogenicity was observed in gravid rats receiving 
daily IV paclitaxel doses of 1 mg/kg (a daily dose of approximately 3 times the dose of the largest 
Lutonix Drug Coated Balloon, adjusted for body surface area). Use of the test or control devices 
in women who are of childbearing potential or in men intending to father children should therefore 
take reproductive risk into careful consideration. 
4.2 RISK MANAGEMENT PROCEDURES 
Eligibility criteria have been selected that exclude patients who are at a higher risk for 
experiencing an anticipated adverse event in order to reduce the risks to subjects who participate in 
this study. In addition, subjects enrolled in this study will receive a defined anti-platelet regimen 
and are required to follow the pre-specified clinical follow-up schedule described in Section 7. In 
addition, follow-up duplex ultrasound will be performed to assess the target vessel patency, and all 
adverse events are formally monitored and independently adjudicated. 
Extensive reliability engineering testing has been performed on the Lutonix Drug Coated Balloon 
to help mitigate any risks to the subjects due to product failure. Additionally, animal studies using 
the Lutonix Drug Coated Balloon have been conducted to ensure that the device performs as 
intended without introducing more risks during the interventional procedure. 
Investigational device training will be conducted at each initiated study center and appropriate 
training records will be maintained. 
4.3 POTENTIAL BENEFITS 
There are no guaranteed benefits from participation in this study; however, it is possible that 
treatment with the Lutonix Drug Coated Balloon may reduce the potential for restenosis of the 
lesion, thereby reducing the need for repeat hospitalization and/or procedure(s). 
Additionally, information gained from the conduct of this study may be of benefit to others with 
the same medical condition. As with all investigational medical devices, the long-term results of 
using the Lutonix Drug Coated Balloon are not known at the present time. Alternatives to the use 
of the Lutonix Drug Coated Balloon include standard or cutting balloon angioplasty, vascular 
stenting, atherectomy, cryoplasty, or vascular radiation and surgery (vessel bypass with native or 
synthetic vessel). Lutonix believes that the risk for significant injury or death due to the Lutonix 
Drug Coated Balloon is extremely low, and the potential benefits of decreased restenosis and 

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decreased need for reintervention is likely, but these potential risks and benefits have yet to be 
quantified. 
4.4 EARLY TERMINATION 
Lutonix, Inc. (Sponsor) and the Clinical Events Committee (CEC) will monitor the progression of 
the study. If warranted, the study may be suspended or discontinued early if there is an 
observation of serious adverse reactions presenting an unreasonable risk to the study population. 
The Sponsor may terminate Investigator and site participation in the study for issues including but 
not limited to the following issues: 
• Evidence of an Investigator’s failure to maintain adequate clinical standards 
• Evidence of an Investigator or staff’s failure to comply with the protocol 
• Inaccuracy or late submission of data forms and core lab images 
• Conditions of approval imposed by the reviewing IRB/EC and/or regulatory 
agencies 
• Evidence of safety concerns or protocol non-compliance 
• Change of staff at site that adversely impacts trial conduct 
Any evident pattern of non-compliance with respect to these standards will be cause for the site to 
be put on probation. If corrective actions are not subsequently undertaken, the clinical site will be 
asked to withdraw from the study and their site may be replaced. 
Notification of suspension or termination will occur no later than five (5) working days after the 
Sponsor makes the determination. In the event of study suspension or termination, the Sponsor 
will send a report outlining the circumstances to the Institutional Review Board (IRB)/Ethics 
Committee (EC), and all Investigators and Regulatory Authorities as required by regulation. A 
suspended or terminated study may not be reinitiated without approval of the reviewing IRB/EC 
and Regulatory Authorities, as required by regulation. 
The Investigator must notify the IRB/EC in writing as soon as possible but no later than within 10 
days if the premature termination is related to safety or compliance issues. 
5 CLINICAL STUDY DESIGN 
The study will enroll subjects presenting with claudication or ischemic rest pain and an 
angiographically significant lesion in the superficial femoral or popliteal artery and a patent 
outflow artery to the foot. After successful protocol-defined pre-dilatation, subjects that are 
unlikely to require a stent based on strict angiographic criteria (absence of major flow-limiting 
dissection from the lumen and ≤70% residual stenosis or the lesion is not appropriate for stenting 
due to proximity to the knee joint) will be treated with the Lutonix Drug Coated Balloon. 
Subjects that do not meet post-predilatation criteria are excluded (and treated per standard practice) 
and followed for safety only (via telephone or clinical follow up) for 30 days. Treated subjects 

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will have ultrasound and clinical follow-up through 2 years and telephone follow-up through 5 
years. 
 
Figure 3 contains an overview of the study. 

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Figure 3: Study Flowchart 
 
 
5.1 SCREENING PROCEDURES 
All patients admitted for a percutaneous revascularization of a femoropopliteal artery should be 
screened for study eligibility. If inclusion criteria are met and no exclusion criteria are present at 
the time of screening, the patient should be entered into a study Screening Log. Once the patient’s 
eligibility has been determined, the Investigator will discuss the study and ask the patient to 
participate. Prior to enrollment, the patient must sign the informed consent form approved for use 
by the IRB/EC or other appropriate committee. A copy of the signed and dated Informed Consent 
will be provided to the subject. Subjects will be assured that they may withdraw from the study at 
any time and for any reason. The background and purpose of the study, participation 
requirements, as well as the potential benefits and risks of the procedure(s) must be explained to 
the subject. 

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The status of all patients screened, whether enrolled, withdrawn, etc., should be captured on the 
study Screening Log for tracking and reporting purposes. 
If not already performed as standard practice, the following assessments and tests must be 
performed after obtaining informed consent and prior to the index procedure (within 30 days 
unless otherwise noted) to verify and complete eligibility: 
• Physical examination (including blood pressure, heart rate, and temperature) 
performed by either an MD, Physician’s Assistant, or Nurse Practitioner 
• Relevant medical history 
• Rutherford Classification 
• Blood analysis 
o CBC with differential (hemoglobin, hematocrit, platelets and leukocytes) 
(differential: neutrophils, lymphocytes, monocytes and basophils) 
o BMP 
▪ Glucose 
Calcium 
▪ Electrolytes (chloride, sodium, potassium) 
▪ Kidney (BUN, creatinine) 
o Pregnancy Test (blood or urine; if female of child bearing potential) 
• Resting Ankle-Brachial Index (ABI) (within 90 days) 
5.2 PATIENT SELECTION FOR ENROLLMENT 
Subjects must meet all the clinical eligibility criteria, agree to participate and comply with study 
protocol requirements and follow-up schedule, and provide informed consent. 
All subjects are expected to remain available (geographically stable) for the duration of the study 
follow-up period. If any subject moves away, every effort must be made to maintain the follow-up 
schedule including having an appropriate physician follow the subject. The Investigator is 
responsible for ensuring that each follow-up visit occurs at the specified time and that all 
applicable data is reviewed and entered into the electronic case report form system (eCRF) in a 
timely fashion. 
5.2.1 
CASE PROCTORING REQUIREMENTS 
Each investigator enrolling in the study must undergo formal Lutonix Drug Coated Balloon 
procedure proctoring with a sponsor representative (or designee) during their initial study Lutonix 
Drug Coated Balloon case(s). The sponsor reserves the right to limit the number of investigators 
performing the study procedure at a site and can expand case proctoring requirements as necessary 
to ensure compliance. 

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≥1 cm below 
bifurcation 
≤2 cm below t. plateau 
& 
≥1 cm above TP 
5.3 SUBJECT INCLUSION AND EXCLUSION CRITERIA 
5.3.1 
INCLUSION CRITERIA 
Subjects must meet all inclusion criteria to be enrolled in the study. 
Clinical Criteria 
1. 
Male or non-pregnant female ≥18 years of age; 
2. 
Rutherford Clinical Category 2-4; 
3. 
Patient is willing to provide informed consent, is geographically stable and comply with 
the required follow up visits, testing schedule and medication regimen; 
Angiographic Criteria 
Lesion Criteria 
4. 
Length ≤15 cm; 
5. 
Up to two focal lesions or segments within the designated 15 cm length of vessel may 
be treated (e.g. two discrete segments, separated by several cm, but both falling within 
a composite length of ≤15 cm); 
6. 
≥70% stenosis by visual estimate; 
7. 
Lesion location starts ≥1 cm below the common femoral bifurcation and terminates 
distally ≤2 cm below the tibial plateau AND ≥1 cm above the origin of the TP trunk; 
 
 
FIGURE 4: ALLOWED LESION LOCATION 
 
8. 
de novo lesion(s) or non-stented restenotic lesion(s) >90 days from prior angioplasty 
procedure; 
9. 
Lesion is located at least 3 cm from any stent, if target vessel was previously stented; 
10. 
Target vessel diameter between ≥4 and ≤6 mm and able to be treated with available 
device size matrix; 
11. 
Successful, uncomplicated (without use of a crossing device) antegrade wire crossing 
of lesion; 
12. 
A patent inflow artery free from significant lesion (≥50% stenosis) as confirmed by 
angiography (treatment of target lesion acceptable after successful treatment of inflow 
artery lesions); 

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NOTE: Successful inflow artery treatment is defined as attainment of residual diameter 
stenosis ≤30% without death or major vascular complication. 
13. 
At least one patent native outflow artery to the ankle, free from significant (≥50%) 
stenosis as confirmed by angiography that has not previously been revascularized 
(treatment of outflow disease is NOT permitted during the index procedure); 
14. 
Contralateral limb lesion(s) cannot be treated within 2 weeks before and/or planned 30 
days after the protocol treatment in order to avoid confounding complications; 
15. 
No other prior vascular interventions within 2 weeks before and/or planned 30 days 
after the protocol treatment. 
5.3.2 
EXCLUSION CRITERIA 
Patients will be excluded if ANY of the following conditions apply: 
 
1. 
Pregnant or planning on becoming pregnant or men intending to father children; 
2. 
Life expectancy of <5 years; 
3. 
Patient is currently participating in an investigational drug or other device study or 
previously enrolled in this study; 
NOTE: Enrollment in another clinical trial during the follow up period is not allowed. 
4. 
History of hemorrhagic stroke within 3 months; 
5. 
Previous or planned surgical or interventional procedure within 2 weeks before or 
within 30 days after the index procedure; 
6. 
History of MI, thrombolysis or angina within 2 weeks of enrollment; 
7. 
Rutherford Class 0, 1, 5 or 6; 
8. 
Renal failure or chronic kidney disease with MDRD GFR ≤30 ml/min per 1.73 m2 (or 
serum creatinine ≥2.5 mg/L within 30 days of index procedure or treated with dialysis); 
9. 
Prior vascular surgery of the index limb, with the exception of remote common femoral 
patch angioplasty separated by at least 2 cm from the target lesion; 
10. 
Inability to take required study medications or allergy to contrast that cannot be 
adequately managed with pre- and post-procedure medication; 
11. 
Anticipated use of IIb/IIIa inhibitor prior to randomization; 
12. 
Ipsilateral retrograde access; 
13. 
Composite lesion length is >15 cm or there is no normal proximal arterial segment in 
which duplex flow velocity can be measured; 
14. 
Significant inflow disease. Successful treatment of inflow disease allowed prior to 
target lesion treatment; 
15. 
Known inadequate distal outflow (>50% stenosis of distal popliteal and/or all three 
tibial vessels), or planned future treatment of vascular disease distal to the target 
lesion; 

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16. 
Sudden symptom onset, acute vessel occlusion, or acute or sub-acute thrombus in target 
vessel; 
17. 
Severe calcification that renders the lesion undilatable; 
18. 
Use of adjunctive primary treatment modalities (i.e. laser, atherectomy, cryoplasty, 
scoring/cutting balloon, etc.). 
6 STUDY/TREATMENT PROCEDURES 
6.1 ENROLLMENT 
A subject is considered enrolled in the study after both of the following steps have occurred: 
• Baseline angiographic confirmation that the target lesion meets all appropriate 
inclusion/exclusion criteria. 
• Defined pre-dilatation balloon inflation has begun. 
 
Subjects that do not meet post-predilatation criteria are enrolled but treated per standard practice 
and followed for safety for 30 days via telephone or clinical visit. Subjects with target lesions that, 
after baseline angiography, do not meet all inclusion/exclusion criteria and are not pre-dilated per 
protocol are considered screen failures and will not be enrolled or treated with the Lutonix Drug 
Coated Balloon in this study. 
 
6.2 LUTONIX DRUG COATED BALLOON INSTRUCTIONS FOR USE (IFU) 
Always follow the current IFU packaged with the device for procedural information, preparation 
and use of the Lutonix Drug Coated Balloon. Any devices found to be defective or that do not 
perform as expected should be returned immediately to the Sponsor for evaluation and a Device 
Malfunction Form must be completed. 
A balloon compliance chart is included on each device product label. 
If more than one Lutonix Drug Coated Balloon will be needed to treat the entire pre-dilated 
segment(s)/lesion(s), the combination of lengths available should be carefully considered 
beforehand to ensure complete coverage of the target lesions (within the maximum length of 
15cm) and, at the same time, reduce unnecessary vessel dilatation. The IFU also contains detailed 
information on lesion coverage and minimal inflation times. 
 
 
6.3 BASELINE ANGIOGRAM 
DSA- or Cine- angiograms should be obtained per core lab guideline. Standard off-line QVA 
acquisition procedures will be followed for analysis at the independent Imaging Core Laboratory. 
All angiography procedures (both index and non-scheduled) must be recorded in such a way that 

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they are suited for off-line QVA. For purposes of ensuring protocol compliance, all angiograms 
must be submitted to the core laboratory as soon after the case as possible. 
 
 
6.4 IN-FLOW LESION TREATMENT 
Absence of inflow disease (≥50% stenosis) as confirmed by angiography is required for enrollment 
in the study. Enrollment is allowed following complete successful treatment per standard practice 
of inflow artery lesions, with successful treatment defined as attainment of a residual diameter 
stenosis ≤30% without death or major vascular complication. 
 
 
6.5 PRE-DILATATION 
Always refer to the current IFU packaged with the Lutonix Drug Coated Balloon for complete pre- 
dilatation requirements. 
Lesion(s) pre-dilatation(s) is required for all patients. The predilatation balloon should be a 
standard PTA balloon inflated to a diameter approximately 1 mm less than the reference vessel 
diameter (RVD). Always limit the longitudinal length of the pre-dilatation balloon to avoid 
creating a region of vessel injury that is outside the boundaries of the area to be treated by the 
Lutonix Drug Coated Balloon (i.e. geographical miss). In order to reduce dissections and potential 
subject allocation to the standard practice arm after pre-dilatation, careful and controlled pre- 
dilatation(s) inflations should be performed and recorded (on film). 
See Table 3 for an overview of lesion assessment. If, after pre-dilatation, the lesion site has a major 
flow-limiting dissection or residual stenosis >70%, the subject will not be treated with the Lutonix 
Drug Coated Balloon but is instead treated per institutional standard practice. Subjects that are 
excluded from treatment with the Lutonix Drug Coated Balloon after pre-dilatation will be 
followed for 30 days for safety and then withdrawn. 
TABLE 3: POST PRE-DILATATION LESION(S) CRITERIA 
Angiographic Condition 
Treatment 
Major Flow Limiting Dissection 
-OR- 
Residual Stenosis >70% 
Excluded, not treated with 
Moxy Drug Coated 
Balloon, and followed for 
safety through 30 days 
Residual Stenosis ≤70% and Absence of Flow-Limiting 
Dissection 
-OR- 
Lesion is not appropriate for stenting due to proximity to the knee 
joint 
Treatment with the 
Lutonix Drug Coated 
Balloon 

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6.6 TREATMENT 
6.6.1 
TREATMENT WITH LUTONIX DRUG COATED BALLOON 
Please refer to the current Lutonix Drug Coated Balloon IFU for detailed information on device 
use. 
The Investigator should determine the appropriate size of the balloon to be used by online QVA (if 
possible) or by visual estimate. The Lutonix Drug Coated Balloon should extend at least 5 mm 
proximally and distally of the pre-dilatation segment. Care should be taken not to extend the entire 
injury segment unnecessarily. 
6.7 POST TREATMENT AND PROVISIONAL (BAILOUT) STENTING PROCEDURES 
The rate of provisional (i.e. bailout) stenting in prior SFA clinical trials, including those 
investigating drug coated balloons, has varied considerably. In particular, a discrepancy has been 
noted in bailout rates between control and treatment arms in previous studies. This discrepancy is 
likely attributable to investigator bias that the control arm is less likely to succeed and thus the 
threshold for stenting test-device treated subjects is lower. There is no consensus or established 
objective criteria that are validated regarding the appropriate threshold for provisional SFA 
stenting. In the absence of an established threshold, the determination to bailout has previously 
been based on criteria that are either subjective or largely left to the discretion of the individual 
operator and his/her judgment. 
The current trial design is intended to minimize the need for bailout stenting. Due to the need 
within the medical community to establish validated criteria for provisional stenting, this trial will 
utilize more rigorous criteria for bailout stenting. Specifically, the trial will employ the additional 
requirement of a pressure gradient measurement to document an unsatisfactory balloon-only 
outcome (obtained by measuring pressures proximal and distal to the lesion simultaneously). The 
minimum pressure gradient threshold for bailout stenting (Table 4) has been established by 
consulting a number of experts who have extensive experience with SFA intervention, some of 
whom utilize pressure gradients routinely in their practices. Requiring confirmation of a baseline 
pressure gradient prior to stenting establishes objective criteria that must be met for bailout 
stenting (and should reduce the rate in this study). 
TABLE 4: PROVISIONAL (BAILOUT) CRITERIA 
Bailout Prevention 
Treatment requirement prior to bailout stenting: 
• 
Prolonged (>2 minutes) balloon inflation(s) 
• 
Vasodilators and/or thrombolytic agents per investigator discretion 
Bailout Criteria 
• 
Residual stenosis of >50% (based on careful in-lab review of angiograms including QVA if 
available) or major flow-limiting dissection (Record angiography in 2 orthogonal views) 
and 
• 
Documented translesional pressure gradient of >20mmHg (using ≤4F end-hole catheter) or 

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These criteria are set as the minimum baseline pressure gradient requirement for allowing bailout 
stenting; however, bailout stenting is not required for pressures equal to or exceeding these 
thresholds (i.e. presence of a gradient at/above these thresholds does not require that the operator 
place a stent). Rather, these thresholds are seen as minimum requirements for bailout stenting; 
below these thresholds, bailout stenting is not allowed. 
If the criteria for bailout stenting are fulfilled, placement of a bare nitinol stent approved by the 
FDA for use in the SFA is allowed. The physician should use the shortest stent possible to treat 
only the clinically significant dissection or residual stenosis and not the entire target lesion. 
Antiplatelet therapy should be prescribed per the stent manufacturer’s IFU. 
The angiographic core lab and study steering committee will be monitoring cases of bailout 
stenting throughout the course of enrollment for compliance to provisional (bailout) criteria listed 
in this section. 
6.8 UNSCHEDULED ANGIOGRAPHY/REVASCULARIZATION 
A DUS is required prior to any subsequent angiography of the index limb, and the images must be 
submitted to the DUS Core Lab. ABI and Rutherford Classification are to be assessed prior to any 
re-intervention of the target limb. In the event that a subject undergoes repeat angiography after the 
index procedure is complete, all subsequent angiograms for the index limb or, in the event of an 
index limb revascularization, all procedural angiograms must be forwarded to the Angiographic 
Core Lab for review and analysis. Attempts should be made to record the same views and angles 
as from the index procedure.  Treatment of any new non-target lesions is left to the discretion of 
the Investigator however, use of drug-device combination products (e.g. DES or DCB) is not 
recommended within 90 days of the index procedure. 
 
7 TREATMENT OF SUBJECT 
Lutonix (or its designee) reserves the right to attend index or DUS procedures in order to ensure 
protocol compliance, proper device handling and adequate image capture. 
7.1 MEDICATIONS 
Table 5 displays the required medication regimen for this study. All medications administered will 
be recorded in the subject’s medical record. These medication and schedules are consistent with 
standard hospital practice. Details of each requirement can be found in the sections below. In 
subjects ≥75 years of age and/or <60kg, prasugrel is generally not recommended because of the 
increased risk of fatal and intracranial bleeding and uncertain benefit, except in high-risk situations 
>10mmHg (pressure wire) measured immediately distal to the target lesion 

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(diabetes or history of prior MI) where its effect appears to be greater and its use may be 
considered. Always refer to the current package insert. 
 
 
TABLE 5: MEDICATION SCHEDULE 
Drug 
Pre-Procedure 
Procedure 
Post-Procedure* 
Aspirin 
75-325 mg/day 
NA 
75-100 mg/day indefinitely 
Clopidogrel 
OR 
Prasugrel*** 
OR 
Ticgrelor 
75 mg or 300 mg 
loading dose 
NA 
75 mg daily for at least 1 month. 
10 mg/day or 
loading dose of 60 
mg 
NA 
for at least 1 month (discontinue with 
active bleeding) 
>60 kg - 10 mg/day 
<60 kg - 5 mg/day** 
90 mg (twice daily) 
or loading dose of 
180 mg 
NA 
90 mg twice daily for at least 1 
month 
Anticoagulation 
Per Hospital Standard Practice 
*For cases of provisional (bailout) stenting, refer to the Stent IFU for dosing instructions 
**The effectiveness and safety of this dose has not been prospectively studied 
***Ticlodipine use per label is an acceptable alternative only if Clopidogrel,Prasugel, nor Ticgrelor are appropriate 
 
7.1.1 
PRE-PROCEDURE 
Subjects that are already taking daily chronic aspirin therapy should receive a dose of 75-325 mg 
aspirin within 24 hours prior to the index procedure. Those subjects not already taking daily 
chronic aspirin therapy should be given at least 300 mg aspirin at least 2 hours and preferably 24 
hours before the procedure is performed. 
If the subject is known to be receiving a stent for a non-target lesion (i.e. inflow lesion), it is 
suggested that 3 days before the intervention clopidogrel (75 mg per day) prasugrel (10 mg per 
day) or ticgrelor (180 mg per day) be prescribed. The initial loading dose of clopidogrel, prasugrel, 
or ticgrelor should attempt to be started prior to the index procedure, but must occur no later than 2 
hours after the completion of the index procedure. 
7.1.2 
INTRA-PROCEDURE 
All subjects must receive adequate anticoagulation according to hospital standard practice. 
7.1.3 
POST-PROCEDURE 
Approved vascular closure devices are allowed. Clopidogrel (75 mg/daily) prasugrel (5-10 
mg/daily), or ticgrelor (90 mg/twice daily) must be prescribed for at least 1 month, unless a stent is 
placed, in which case antiplatelet therapy should be prescribed per the stent manufacturer’s IFU. 
Updated guidelines will be implemented via note-to-file if changes in the recommended doses 
occur. 

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7.2 STANDARD TESTS, PROCEDURES, AND FOLLOW-UP 
Table 6 displays the required schedule for subject treatment and evaluation. This schedule is 
consistent with standard clinical care pre- and post-interventional procedures. The times for each 
test are broad enough to fit into most hospital routine testing procedures. 
Subjects enrolled, and treated per standard practice will be followed for safety through 30 days. 
The 30 day follow-up visit can be performed as a telephone or clinical visit. Duplex ultrasound 
imaging is not a protocol requirement for this group. Details of each testing requirement can be 
found in the sections below. 
Table 6: Follow-Up Schedule and Testing Requirements for treated subjects 
 
Event 
Screening 
(pre-consent) 
Pre- 
Procedure 
Procedure 
Post- Procedure 
1 Month1 
6 Month 
12 Month 
24 Month 
36 Month1 
48 Month1 
60 Month1 
Visit Window 
30 
days 
30 
days 
±2 
weeks 
±1 
month 
±1 
month 
±2 
month 
±2 
month 
±2 
month 
±2 
month 
Inclusion/Exclusion Criteria 
√ 
√ √ 
Informed Consent 
√ 
Medical History 
√ 
Physical Exam2 
√ 
√ 
√3 
√ 
√ 
√ 
Medication Compliance 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Resting ABI 
√4 
√4 
√4 
√ 
√ 
√ 
Rutherford Classification 
√ 
√ 
√ 
√ 
Blood Analysis (CBC with 
differential; BMP, pregnancy6) 
√5 
√ 
√3 
√ 
√ 
Angiogram 
√ 
Adverse Event Monitoring 
√ √ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Duplex Ultrasound (after 
clinical assessment) 
√7 
√ 
√ 
√ 
1Follow-up can be by telephone or clinical visit, depending on timing of duplex ultrasound (if required) 
2 Physical Exam must be performed by and MD, PA, or NP 
3Required if clinical visit occurs 
4Resting ABI is required within 90 days of index procedure. Resting ABI is not required post procedure or at 1-month, 
but investigator encouraged to capture if possible 
5Pre-procedure blood analysis must be performed within 30 days of the procedure 
6Pre-procedure and females of childbearing potential only 
7Baseline duplex is only required once (anytime post-procedure through the 1-month visit) 
 
At 6, 12, and 24 month follow-up visits, the clinical status of the subject (for assessment of clinical 
and safety endpoints) should be established prior to performing the required DUS (for assessment 
of patency). 

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7.2.1 
TESTING 
7.2.1.1 
LABORATORY TESTING 
Laboratory samples must be drawn pre-procedure, post-procedure, and at the 6 and 12-month 
clinical visits. All laboratory values must be recorded on the appropriate study eCRFs. Pre- 
procedure samples may be taken up to 30 days prior to the index procedure. 
Laboratory test reporting requirements include: 
• CBC with differential (hemoglobin, hematocrit, platelets and leukocytes) 
(differential: neutrophils, lymphocytes, monocytes and basophils) 
• BMP 
o Glucose 
o Calcium 
o Electrolytes (chloride, sodium, potassium) 
o Kidney (BUN, creatinine) 
• Pregnancy Test (blood or urine; if female of child bearing potential) 
7.2.1.2 ANKLE-BRACHIAL INDEX (ABI) 
A resting ABI must be performed per local hospital standard, and consistently among subjects over 
the lifespan of the study. 
7.2.1.3 RUTHERFORD SCALE 
Rutherford classification can be measured with or without treadmill, but must be performed 
consistently among subjects over the lifespan of the study. 
7.2.1.4 DUPLEX ULTRASOUND AND ANGIOGRAPHY GUIDELINES 
The initial baseline DUS must be performed after the index procedure (up to 1 month ±2 weeks 
post-procedure), and again at 6, 12 and 24 months. Since DUS is critical to assessing study 
endpoints, the quality of this test is extremely important. The Core Labs will be closely 
monitoring the quality of all incoming images for compliance. Sites should ensure that only DUS 
operators who are trained on the protocol and DUS guidelines are performing these tests. Refer to 
the Duplex Ultrasound and Angiography Guidelines Manual of Operations for the most current 
version of the documentation requirements. See Appendix I and Appendix J for detailed core lab 
guidelines. 
7.2.2 
FOLLOW-UP PROCEDURES 
The Investigator or Research Coordinator will contact treated subjects via phone (or via clinical 
visit if preferred or as part of a regular follow-up) at approximately 1 month, 36 months, 48 
months and 60 months (and possibly longer if required) in order to assess for any adverse events 
and medication compliance. 

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Alltreated subjects will return for follow-up at 1 (if required for duplex ultrasound), 6, 12 and 24 
months post procedure. See Table 6 for required testing at each follow-up visit time point. 
Following randomization, all subjects are required to complete all assigned follow-up visits and 
procedures. During the duration of the study, all events need to be reported in the web-based 
eCRF. Subjects will be instructed to report adverse events to their study physician between 
evaluation visits. 
Relevant medications will be recorded on the eCRF. Anti-platelet therapy compliance including 
dose, periods of interruption (and reason for interruption), and invasive procedures deterred due to 
the need to take anti-platelet therapy will also be recorded on the eCRF. 
8 ADVERSE EVENTS 
An adverse event (AE) is defined as any untoward medical occurrence in a subject. This definition 
does not imply that there is a relationship between the adverse event and the device under 
investigation. See Appendix A for detailed AE definitions. 
8.1 ADVERSE EVENT REPORTING 
All adverse events occurring since the start of the study procedure must be recorded in the eCRF. 
All serious adverse events will be reviewed and adjudicated by the Clinical Events Committee to 
determine whether it is related to the device or procedure. All adverse events occurring in this 
study will be classified in accordance with the adverse event signs or symptoms. Any Serious 
Adverse Event must be reported to Lutonix or designee within 24 hours of knowledge. All adverse 
events will be reported to the IRB/EC per local requirements. 
9 SUBJECT WITHDRAWAL CRITERIA 
Subjects can withdraw from the study at any time for any reason; the reason for withdrawal will be 
documented. All data available at the time of withdrawal (if any) will be used for analysis. There 
will be no further follow-up (per this study protocol) on the subject who has withdrawn. Subjects 
who withdraw from the study will not be replaced, however loss-to-follow-up has been considered 
for sample size statistics. 
If a visit is missed, the site is required to document a minimum of three (3) attempts to contact the 
subject within the follow-up window. If the subject only misses one protocol required visit, the 
site should repeat the three (3) attempts to contact the subject followed by a certified letter. When 
a subject misses two (2) consecutive follow-up visits with failure of all contact attempts, the 
subject may then be considered lost to follow up and exited from the study. 

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10 DATA COLLECTION AND MONITORING 
10.1 DATA COLLECTION 
The Investigator (or designated hospital staff) will assure primary data collection based on source- 
documented hospital chart reviews. These documents will be completed in an expedited fashion. 
10.1.1 ELECTRONIC CASE REPORT FORMS (ECRF) 
All required clinical data for this trial will be collected in web-based standardized eCRFs. Clinical 
trial data will be collected in accordance with the Guidance for Industry: Collection of Race and 
Ethnicity Data in Clinical Trials. Subject personal information should be blinded. Site numbers, 
subject numbers and initials will be used to track subject information throughout the study. 
The eCRF is designed to accommodate the specific features of the study design. Modification of 
the eCRF will only be made if deemed necessary by Lutonix and/or the appropriate regulatory 
body. 
10.1.2 ANGIOGRAMS AND DUPLEX ULTRASOUNDS 
All core lab raw data will be sent to the independent Core Lab listed in the study summary. A 
specific algorithm will be used to analyze each core lab result. This information will be 
documented on a study form and the data transmitted to Data Management for integration into the 
main study database. 
10.2 MONITORING 
A formal written Monitoring Plan will be developed in accordance to FDA guidelines 53 CFR 
4723 and the study protocol by the CROs appointed for this study and approved by Lutonix. 
Appropriately trained and qualified monitoring personnel will monitor the progress of this study. 
Prior to protocol submission to the site, a formal pre-qualification visit will be conducted by a 
Lutonix employee or designee at sites who have not previously been involved in Bard or Lutonix- 
sponsored trials. Pre-qualification visits are done to confirm the appropriate staff, experience, 
resources, equipment, and patient population exist for this protocol. 
Each site will have an initiation visit performed by a Study Monitor and a member of the Lutonix 
clinical staff. This visit will ensure that the investigator understands his/her responsibility for 
conducting this study at his/her center. This includes, but is not limited to, device accountability, 
protocol compliance, informed consent process, enrolling appropriate subjects, and IRB/EC 
submissions, approvals, and continuing reviews. 
Monitoring will be performed on original medical records of all enrolled subjects. Sites will be 
monitored according to the approved monitoring plan. Monitoring personnel will monitor for 
accuracy and timely submission of data forms and core lab images, and compliance with the study 
protocol, meeting enrollment commitments, applicable regulations, the signed Investigator 
Agreement and any conditions of approval imposed by the reviewing IRB/EC and/or regulatory 

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agencies. Monitoring personnel will also confirm documentation of the informed consent process, 
missing visits or examinations, and the reason for any subject failing to complete the study. 
Any evident pattern of non-compliance with respect to these standards will be cause for the site to 
be put on probation. If corrective actions are not subsequently undertaken, the clinical site will be 
asked to stop enrollment and complete outstanding follow-up visits for subjects already enrolled at 
their site. 
Monitoring visits will be scheduled based on the enrollment rate at each site, duration of the study, 
compliance, and any suspected inconsistency in data that requires investigation. 
The Study Monitors will maintain personal contact with the Investigator and staff throughout the 
study by phone, mail, and on-site visits. The Study Monitors will compile and submit to Lutonix a 
monitoring report after each visit which will include any findings, conclusions, and actions taken 
to correct deficiencies. Specifically, the Study Monitors will review: 
• Screening Procedures 
• Study Treatments 
• Discontinuation of Treatment 
• Source Data 
• Adverse Event/Serious Adverse Event Recording and Reporting 
• Investigational Device Reconciliation 
• Study Data and Core Lab Data Submission 
• Protocol Deviations 
At the close of the study at an investigational site, appropriately trained personnel appointed by 
Lutonix will make a final on-site visit. The purpose of this visit is to collect all outstanding study 
data documents, ensure that the Investigator's files are accurate and complete, review record 
retention requirements with the Investigator, make a final accounting of all study supplies shipped 
to the Investigator, provide for appropriate disposition of any remaining supplies, and ensure that 
all applicable requirements are met for the study. The observations and actions made at this visit 
will be documented and communicated to the Investigator. 
10.3 SOURCE DOCUMENTATION 
Auditors, monitors, medical IRB/ECs, the study Sponsor and regulatory authorities may have 
access to the medical records related to this study. Original or certified copies of all relevant 
clinical findings, observations, and other activities throughout the clinical investigation must be 
recorded and maintained in the medical file of each enrolled subject. (No source documentation 
will be recorded directly on a CRF). At a minimum, the following must be included in each 
subject’s file: 

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• Sufficient medical history and current physical condition, including any 
medication(s) the subject is taking at the time of the procedure to assess the 
subject’s eligibility; 
• The medical file should reveal the subject’s participation in this study, including 
start and expected follow-up time; 
• Dated report of the investigational procedure including medication, material 
usage, and complications, if applicable; 
• Dated reports of the discharge and follow-up assessments; 
• Dated results of required laboratory tests; 
• Any adverse event(s), the resultant action or treatment, and outcome, if 
applicable; and 
• In the case of withdrawal of subject consent, reason and subject status at time of 
withdrawal. 
The Investigator will permit study–related monitoring, audits, IRB/EC review and authority 
inspections by allowing direct access to the source data. 
In case of electronic source data, access will be allowed or dated print-outs will be available prior 
to the monitoring visits. Print-outs should not be limited to the vascular data only, but should 
include all available data related to the identified subject(s). 
10.4 RECORD RETENTION 
The Sponsor and Investigator will maintain the following accurate, complete, and current records 
relating to the conduct of the investigation according to national requirements. The data for some 
of these records may be available in computerized form from the CRO, but the final responsibility 
for maintaining study records remains with the Investigator. These include: 
• 
All correspondence with another Investigator, an IRB/EC, a Core Laboratory, 
Lutonix, a monitor, or regulatory agency, including required reports; 
• 
Records of receipt, use, or disposition of the investigational device, including 
receipt dates, serial and/or lot numbers, names of all persons who received or 
used the device, why and how many devices were returned to or otherwise 
disposed of. Device reconciliation logs should be kept current and available to 
Lutonix and monitor upon request; 
• 
Records of each subject's case history, source documents, evidence of informed 
consent, all relevant observations of adverse study device effects, the condition 
of each subject upon entering and during the course of the investigation, 
relevant medical history, the results of all diagnostic testing, and the date of 
each study treatment; 
• 
Screening log, enrollment log, study personnel visit log; 
• 
Any other records that the regulations require to be maintained. 

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10.5 STUDY PROCESSING 
10.5.1 COMMUNICATION 
During the course of the study, regular teleconference calls between Lutonix, the CRO, the Study 
Monitor(s) and each clinical site (if necessary) will be conducted to resolve any problems 
concerning the protocol and data collection. Every effort will be made to ensure compliance with 
the protocol. 
10.5.2 TRAINING 
The training of appropriate clinical site personnel and support staff will be the responsibility of 
Lutonix or their designee. To ensure proper device usage, uniform data collection and protocol 
compliance, Lutonix or their designee will present a formal documented training session(s) to 
study site personnel which will include, but may not be limited to, the following: 
• Techniques for the identification of eligible subjects 
• Investigational Plan 
• Device Training 
• Core lab Instructions 
• Instructions on study and adverse event data collection 
• Schedules for follow-up with the study site coordinators 
• Regulatory requirements 
Detailed feedback regarding completion of forms will be provided by Lutonix or designee, through 
regular site monitoring. 
11 DEVICE ACCOUNTABILITY 
All investigational Lutonix Drug Coated Balloon must be stored in a locked storage facility to 
which only the Investigator and/or designated study staff will have access. The Investigator is 
responsible for device accountability at the trial site. The Investigator may assign the responsibility 
for the device accountability to an appropriate study staff member, but remains the final 
responsible person. The Investigator must ensure that the device is used only in accordance with 
the protocol and current IFU. The Investigator must maintain records that document device 
delivery to the trial site, the inventory at the site and administration to each subject. These records 
must include dates, quantities, batch/serial numbers, expiration dates, and the unique code numbers 
assigned to the trial subjects. The Investigator must maintain records that adequately document 
which device the subject received according to the protocol and the assigned randomization. In the 
case where a device has failed, the Investigator must make every possible effort to return the 
device to Lutonix; instructions for this procedure will be provided in the Manual of Operating 
Procedures. 

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11.1 SUPPLY AND SUPPORT OF INVESTIGATIONAL DEVICE 
An investigational device supply will be made available to all study sites. The device matrix will 
include various diameter and lengths to accommodate the anatomy of the target population. Prior 
to the start of study enrollment, Lutonix or their designee will perform formal device training of 
study site personnel and support staff. Each study site will receive a supply of the Lutonix Drug 
Coated Balloons upon completion of the protocol requirements for study initiation. Additional 
training and support will be provided on an ongoing basis. 
For resupply of Lutonix Drug Coated Balloons, the site is to contact the Sponsor or its designee. 
12 STUDY MANAGEMENT 
The Principal Investigators for this study are Kenneth Rosenfield, MD, Boston, MA, USA and 
Dierk Scheinert, MD, Leipzig, Germany. 
12.1 STEERING COMMITTEE 
The Steering Committee (SC) is the main policy and decision making committee of the study and 
has final responsibility for the scientific conduct. This committee will meet as needed by 
conference or teleconference to monitor enrollment, clinical site progress, and protocol 
compliance. The SC will make decisions by majority vote. The specific tasks of the Steering 
Committee are to: 
• 
Act upon recommendations of the Clinical Events Committee 
• 
Resolve problems in cooperation with the Clinical Trial Manager 
• 
Sole discretion for stopping or otherwise modifying the study based on clinical data 
collected 
• 
Provide publication policy 
• 
Approve study reports and papers for publications (including abstracts) and 
presentations of clinical data of any Investigator 
The Steering Committee will be comprised of representatives from Lutonix, the Principal 
Investigators, core lab directors and non-Investigator physicians representing Interventional 
Cardiology, Vascular Surgery and Interventional Radiology specialties. 
Members of the Steering Committee, in conjunction with the CRO and imaging core laboratories, 
will oversee protocol compliance and implement steps of corrections, actions or warnings letters as 
necessary. Any site found to have major or repeated compliance issues will be contacted by a 
Steering Committee member, or designee, for necessary discussion and/or retraining. The Steering 
Committee may stop enrollment at any site based on compliance or safety issues. 
12.2 CLINICAL EVENTS COMMITTEE 
The Clinical Events Committee (CEC) is made up of a minimum of three clinicians with expertise 
in vascular intervention and who are not participants in the study or members of the SC. The CEC 

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is charged with the development of specific criteria used for the categorization of clinical events 
and clinical endpoints in the study which are based on the protocol. 
At the onset of the trial, the CEC will establish explicit rules outlining the minimum amount of 
data required in order to classify a clinical event. All members of the CEC will be blinded to the 
primary results of the trial. The CEC will meet regularly to review and adjudicate all clinical 
events. The committee will also review and rule on all deaths that occur throughout the trial. 
13 REGULATORY RESPONSIBILITIES 
13.1 IRB APPROVAL 
Investigators must submit the study protocol to their IRB and obtain written approval before being 
allowed to conduct and participate in the study. Annual re-approval must also be obtained. The 
Investigator is also responsible for fulfilling any conditions of approval imposed by the IRB, such 
as regular safety reporting, study timing, etc. The Investigator will provide Lutonix or designee 
with copies of such approvals and reports. 
Any amendments to the protocol, as well as possible associated information and consent form 
changes, will be submitted to the IRB and written approval obtained prior to implementation. 
13.2 INFORMED CONSENT 
Part of the IRB/EC approval must include approval of an Informed Consent Form (ICF) that is 
specific to the study and approved by the FDA and any other relevant regulatory bodies. The 
Investigator must administer this approved ICF to each prospective study subject, and obtain the 
subject's signature on the ICF prior to enrollment in the study. The ICF may be modified to suit 
the requirements of the individual site. The Investigator will provide Lutonix or designee with a 
copy of the approved ICF for his/her site. Lutonix or designee must pre-approve each ICF prior to 
initial submission to the IRB; major changes must be approved by the FDA. 
The study must be explained in a language that is understandable to the subject and he/she must be 
allowed sufficient time to decide whether to participate. All subjects will be assured that they have 
the right to withdraw from the study at any time during the course of the protocol and this decision 
will not influence his/her relationship with the Investigator (treating physician) and/or study staff. 
13.3 SELECTION OF CLINICAL SITES AND INVESTIGATORS 
The Sponsor will select Investigators who are qualified and experienced to participate in the 
investigation of the study devices. Sites will be selected based upon a review of a recent site 
assessment and the qualifications of the (primary) Investigator(s) at the site. Investigators may be 
selected to participate in the study after submitting a current curriculum vitae (CV). 
All Investigators must be approved by the Sponsor prior to participation in the study. 
Any site that becomes deactivated prior to initial enrollment, either by the sponsor or by the 
individual site itself, will be replaced. 

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Due to the potential for an imbalance in the randomization ratio from low enrolling sites, any site 
not able to enroll a subject within 2 months (60 days) of formal initiation will be replaced. The 
sponsor will proactively be tracking site based enrollment throughout the study and may 
implement enrollment restrictions to assist in balanced enrollment across sites. 
13.4 INVESTIGATOR’S RESPONSIBILITIES 
Each Investigator is responsible for ensuring the investigation is conducted according to all signed 
agreements, the Investigational Plan and applicable laws and regulations. The site Principal 
Investigator will select qualified co-investigators at each site and will maintain responsibility for 
oversight of all procedures and data collection. All co-investigators must be trained on all aspects 
of the protocol prior to enrolling and performing procedures. All interventionalists performing 
procedures must be trained as co-investigators in the study. 
The Investigator may not begin enrollment or receive the initial shipment of the investigational 
devices until Lutonix or designee receives appropriate IRB approval and any other applicable 
document (revised investigator agreement, etc.) 
• 
Complete Signed Investigator Agreement 
• 
Financial Disclosure Forms for all participating Investigators 
• 
IRB/EC Roster 
• 
IRB/EC Protocol and Informed Consent Approvals 
• 
Investigators’ and Co-Investigators' current curricula vitae (CV) 
• 
Laboratory Normal Values and Lab Certification 
• 
Site Signature and Responsibility Form 
13.4.1 STUDY COORDINATOR 
To ensure proper execution of the Investigational Plan, each Investigator must identify a Study 
Coordinator for the site. Working with and under the authority of the Investigator, the Study 
Coordinator helps ensure that all study requirements are fulfilled, and is the contact person at the 
site for all aspects of study administration. The Investigator has the ultimate responsibility of all 
study requirements. 
13.4.2 REPORTS 
Table 7 below displays a list of the reports that are the Investigator's responsibility to generate. 
The table also shows to whom the report is to be sent, and with what frequency or time constraints. 
While some of these reports will be developed by or with the assistance of the CRO or Lutonix, the 
final responsibility for them rests with the Investigator. 

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TABLE 7: REPORTS REQUIRED FROM CLINICAL INVESTIGATORS 
Report Type 
Prepared For: 
Time Constraints of Notification 
Subject death during 
investigation 
Lutonix/CRO/IRB/EC To Lutonix/CRO: Verbal within 24 hours and 
written report within 48 hours. 
To IRB/EC: Written documentation of the event 
within 10 working days 
SAE/UADE 
Lutonix/CRO/IRB/EC If serious or life-threatening, within 24 hours by 
email, fax, CRF or phone to Lutonix/CRO, 
followed by a written documentation of the 
event within: 
• 
10 working days to Lutonix/CRO and 
IRB/EC 
Report of subject enrollment CRO 
By Enrollment fax within 24 hours 
Subject withdrawal 
Lutonix/CRO 
Within 5 working days 
Withdrawal of IRB/EC 
approval 
Lutonix/CRO 
Immediately by telephone followed by a copy of 
the notification within 5 working days 
Continuing IRB/EC re- 
approval 
IRB/EC 
Prior to continuing review date. 
Progress report 
Lutonix/CRO/IRB/EC Submitted at regular intervals or annually 
Significant deviations from 
Investigational Plan 
Lutonix/CRO/IRB/EC Within 5 working days 
Failure to obtain ICF 
Lutonix/CRO 
Within 5 working days 
Final summary report 
Lutonix/CRO 
Within 3 months 
13.5 LUTONIX RESPONSIBILITIES 
An Investigator Meeting and site initiation visit will occur with each study site in order to orient 
the Investigator and staff to information such as: the investigational device, the Investigational 
Plan, applicable regulations and requirements, and expectations of the study, including the 
numbers and time frame for subject enrollment, subject selection, informed consent, required 
clinical data, and record keeping. 
Lutonix or designee (CRO) will maintain the following records: 
• All correspondence which pertains to the investigation 
• Signed Investigator Agreements/Compensation Agreements, and Curriculum Vitaes 
• Adverse effects and complaints 
• All Case Report Forms (signed by the Investigator) 
• Investigational Plan 
• Pre-Study Visit Form 
• Monitoring Reports 

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14 PUBLICATIONS 
The trial will be registered in the ClinicalTrials.gov website upon approval by a human subject 
review board of the appropriate national health authorities in order to meet the criteria of the 
International Committee of Medical Journal Editors. All publications will follow the Uniform 
Requirements for Manuscripts Submitted to Biomedical Journals (www.icmje.org, October 2008). 
After the conclusion and final analysis of the trial results, a formal abstract presentation may be 
made at a major cardiovascular conference and the study results, approved by the Principal 
Investigator and the Steering Committee, will be submitted to a reputable scientific journal. 
Following the publication of the main manuscript, secondary analyses proposals will be considered 
for publication from either the Steering Committee members or individual Investigators. Before 
publishing or presenting data from the study, the Research Institution, Principal Investigator, and 
Co-Investigator(s) agree to submit copies of any and all proposed manuscripts or abstracts to 
Lutonix at least 30 days in advance of submitting to a publisher or other third party. No 
submissions may be made without the written approval from Lutonix. 
15 STATISTICAL ANALYSIS PLAN 
15.1 OVERVIEW OF STUDY DESIGN 
The purpose of the LEVANT 2 Safety Registry is to collect additional safety and efficacy 
information of the Lutonix Drug Coated Balloon for treatment of stenosis or occlusion of the 
femoral and popliteal arteries in a large population of subjects. The LEVANT 2 Safety Registry is 
an open-label registry study of the Lutonix Drug Coated Balloon. 
 
 
Approximately 975 combined subjects will be enrolled into both the LEVANT 2 Safety Registry 
and the LEVANT 2 Continued Access Registry in order to include a total of 650 subjects treated 
with the Lutonix Drug Coated Balloon after successful predilatation. Subjects are considered 
enrolled in the study after being consented and the defined pre-dilatation balloon inflation has 
begun. Based on angiographic results after predilatation, up to 1/3 of pre-dilated subjects are not 
expected to meet criteria for enrollment and will be treated per standard of care. Enrollment will 
continue only until a sample size of 650 DCB-treated subjects is achieved. 
 
 
The Primary Endpoint is the rate of unanticipated device- or drug- related adverse events over time 
through 60 months.  Secondary endpoints include the rate at 1, 6, 24, 36, 48, and 60 months and 
the primary and majority of the secondary endpoints of the LEVANT 2 Randomized Study. 

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15.2 
SAMPLE SIZE JUSTIFICATION 
Taken together with the LEVANT 2 Randomized Study, the 650 additional combined DCB 
subjects enrolled in the LEVANT 2 Safety Registry and the LEVANT 2 Continued Access 
Registry will provide a safety dataset on 1022 subjects treated with the Lutonix Drug Coated 
Balloon, since the LEVANT 2 Randomized Protocol includes approximately 55 roll-ins and 317 
test subjects randomized to drug coated balloon. 
Allowing for up to 15% loss-to-follow-up, an evaluable sample size of 869 test subjects is 
expected.  If the observed rare adverse event rate is 1%, then the upper limit of the 95% 
Confidence Interval is 1.8% (PASS2008: Exact Clopper-Pearson). Assuming an expected 1% 
incidence rate, Power is > 95% to observe at least 4 unexpected SAEs (PASS2008: Post-Marketing 
Surveillance). Similarly, if the observed rate is 2%, then the upper limit of the 95% Confidence 
Interval is 3.0%. Assuming an expected 2% incidence rate, Power is > 95% to observe at least 11 
unexpected SAEs. This study provides the ability to detect and describe the rate of rare 
unanticipated adverse events with some precision. 
 
15.3 
ANALYSIS 
Data from all the subjects treated with DCB in the LEVANT 2 Randomized protocol (roll-in and 
randomized to DCB), LEVANT 2 Safety Registry and the LEVANT 2 Continued Access registry 
will be combined and analyzed using descriptive statistics. To assess the consistency of results 
under different analyses, secondary as-treated (AT) and per-protocol (PP) analyses will be 
performed for the primary and secondary endpoints. An additional supportive analysis of patients 
with and without bailout stenting will also be performed based on descriptive statistics, and data 
will further be presented for PP analysis of subjects with and without bailout stenting. Poolability 
by geography and by test group (LEVANT 2 Randomized Study roll-ins subjects, randomized 
subjects in the LEVANT 2 Randomized trial, LEVANT 2 Safety Registry subjects and LEVANT 2 
Continued Access Registry subjects) will also be evaluated. 
 
 
In addition to the primary endpoint, all secondary endpoints will also be analyzed using descriptive 
statistics. 

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APPENDIX A: DEFINITIONS 
 
Adverse Event 
An adverse event (AE) is defined as any untoward medical occurrence in a subject. This definition 
does not imply that there is a relationship between the adverse event and the device under 
investigation. 
Adverse Device Effect 
An adverse device effect is any untoward and unintended response to a medical device. 
This definition includes any event resulting from insufficiencies or inadequacies in the 
instructions for use for preparation or deployment of the device. It also includes any event 
that is a result of a user error. 
Anticipated Adverse Event 
Any undesirable health related experience occurring to a subject whether or not considered 
related to the investigational product(s) or drug regimen prescribed as part of the protocol, 
predefined in the protocol and/or Instructions For Use (IFU) that is identified or worsens 
during a clinical study. 
Serious Adverse Event (SAE) 
A SAE is an adverse event that: 
 
• led to death or led to a serious deterioration in the health of the subject 
• resulted in a life-threatening illness or injury, 
• resulted in a permanent impairment of a body structure or a body function, 
• required in-subject hospitalization or prolongation of existing hospitalization or 
• resulted in medical or surgical intervention to prevent permanent impairment to body 
structure or a body function 
All serious adverse events will be adjudicated by the CEC and reported appropriately. 
Serious Adverse Device Effect (SADE) 
A SADE is an adverse device effect that has resulted in any of the consequences 
characteristic of a serious adverse event or that might have led to any of these 
consequences if suitable action had not been taken or intervention had not been made or if 
circumstances had been less opportune. 
 
Unanticipated Adverse Device Effect (UADE) 

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A UADE is “any serious adverse effect on health or safety or any life-threatening problem 
or death caused by, or associated with, a device, if that effect, problem, or death was not 
previously identified in nature, severity, or degree of incidence in the investigational plan 
or application (including a supplementary plan or application), or any other unanticipated 
serious problem associated with a device that relates to the rights, safety, or welfare of 
subjects” (21 CFR 812.3(s)). 
Adverse Event Severity Stratification 
The Investigator will use the following definitions to rate the severity of each adverse 
event: 
 
Mild 
Awareness of a sign or symptom that does not interfere with the 
subject’s usual activity or is transient, resolved without treatment 
and with no sequelae. 
 
Moderate 
Interferes with the subject’s usual activity and/or requires 
symptomatic treatment. 
 
Severe 
Symptom(s) causing severe discomfort and significant impact of 
the subject’s usual activity and requires treatment. 
 
 
Relationship to study device 
The Investigator will use the following definitions to assess the relationship of the adverse 
event to the use of study device: 
 
Not Related The event is definitely not associated with device application. The 
adverse event is due to an underlying or concurrent illness or effect 
of another device or drug. 
Unlikely 
An adverse event has little or no temporal relationship to the study 
device and/or a more likely alternative etiology exists. 
Possible 
The temporal sequence between device application and the event is 
such that the relationship is not unlikely or subject’s condition or 
concomitant therapy could have caused the AE. 
The temporal sequence is relevant or the event abates upon device 
Probable 
 
 
Highly 
Probable 
application completion/removal or the Event cannot be reasonably 
explained by the subject’s condition. 
The temporal sequence is relevant and the event abates upon 
device application completion/removal, or reappearance of the 
event on repeat device application (re-challenge). 

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Relationship to study procedure 
The Investigator will use the following definitions to assess the relationship of the adverse 
event to the use of study procedure: 
 
Not Related 
The event is definitely not associated with procedure. The adverse 
event is due to an underlying or concurrent illness or effect of 
another procedure. 
Unlikely 
An adverse event has little or no temporal relationship to the 
procedure and/or a more likely alternative etiology exists. 
Possible 
The temporal sequence between the procedure and the event is 
such that the relationship is not unlikely or subject’s condition or 
concomitant therapy could have caused the AE. 
The temporal sequence is relevant or the event abates upon 
Probable 
 
 
Highly 
Probable 
procedure completion or the Event cannot be reasonably explained 
by the subject’s condition. 
The temporal sequence is relevant and the event abates upon 
procedure completion, or reappearance of the event on repeat 
procedure (re-challenge). 
 
Abrupt or Acute Closure 
Angiographic documentation of significantly reduced flow due to mechanical dissection, thrombus 
or severe vessel spasm in the treatment area. 
 
Acute Technical Success 
Acute technical success is defined as, a per device basis, the achievement of successful delivery 
and deployment of the study device(s) as intended at the intended target lesion, without residual 
dissections, without visible thrombus, without “watermelon seeding” of the balloon, without 
balloon rupture or inflation/deflation abnormalities and a successful withdrawal of the study 
system. 
 
All Cause Perioperative Death 
All-cause Perioperative Death is defined as death within 30 days of the index procedure. 
 
Amputation of the Index Limb 
Amputation includes all amputations including both Major Amputations (above the ankle) and 
Minor Amputations (including amputations below the ankle). 
 
Ankle Brachial Index Assessment 
Ankle systolic pressure/brachial systolic pressure, measured by constructing a ratio from the peak 
systolic pressure measured during the deflation of the ankle cuffs during Doppler detection to the 
systolic brachial pressure. 

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As-Treated 
The As-Treated analysis is based only on those subjects treated with either an investigational or 
control device, and the comparison is based on the actual device used, not randomized assignment. 
 
Binary Restenosis Rate 
The presence of a hemodynamically significant restenosis (>50%) as determined by angiography 
or by duplex ultrasound (defined by systolic velocity ratio≥2.5). 
Clinically Driven Target Lesion Revascularization 
Revascularization at the target lesion with evidence of target lesion diameter stenosis >50% 
determined by duplex ultrasound or angiography and new distal ischemic signs (worsening ABI or 
worsening Rutherford Category associated with the target limb). 
 
Clinically Driven Target Vessel Revascularization 
Revascularization of the target vessel with evidence of diameter stenosis >50% determined by 
duplex ultrasound or angiography and new distal ischemic signs (worsening ABI or worsening 
Rutherford Category associated with the target limb). 
 
DUS Clinical Patency 
Defined as patency of the target limb (based on a PSVR threshold < 2.5) without prior Clinically 
Driven TLR. 
 
Device Malfunction 
A malfunction is a failure of a device to meet its performance specifications or otherwise perform 
as intended. Performance specifications include all claims made in the labeling of the device. The 
intended performance of a device refers to the intended use for which the device is labeled or 
marketed. 
Device Success 
Acute technical success is defined as, a per device basis, the achievement of successful delivery 
and deployment of the study device(s) as intended at the intended target lesion, without balloon 
rupture or inflation/deflation abnormalities and a successful withdrawal of the study system. If a 
device is inserted into the subject but not used due to user error (e.g. inappropriate balloon length 
or transit time too long), this device will not be included in the device success assessment. 
 
Discharge 
The time point at which the subject was released from the admitting hospital or transferred to 
another facility. 

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Dissections 
National Heart, Lung, and Blood Institute (NHLBI) Dissection Classification System: 
0: None 
A. Minor radiolucencies within the lumen during contrast injection with no persistence after dye clearance. 
B. Parallel tracts or double lumen separated by a radiolucent area during contrast injection with no 
persistence after dye clearance. 
C. Extraluminal cap with persistence of contrast after dye clearance from the lumen. 
D. Spiral luminal filling defects. 
E. New persistent filling defects. 
F. Non-A-E types that lead to impaired flow or total occlusion. 
Note: Type E and F dissections may represent thrombus. 
 
Enrollment 
The point at which the subject has met all the study inclusion and none of the study exclusion 
criteria, the guidewire has been placed across the study lesion and study pre-dilatation has 
occurred. 
 
Intent-To-Treat (ITT) 
The principle of including outcomes of all subjects in the analysis who are randomized into the 
study, regardless of the treatment actually received. 
 
Index Limb Related Death 
Any death adjudicated by the DMC as “likely related” to a complication of the index limb. 
 
Major Bleeding Complications 
Bleeding will be considered major if: 
• It leads to death; 
• It leads to permanent disability; 
• It is clinically suspected or proven to be intracranial (see stroke) 
• It produces a fall in hemoglobin of at least 3 mmol/l; 
• It leads to transfusion of 2 or more units of whole blood of packed cells; 
• Peripheral vascular surgery is necessary. 
• All other bleeding will be considered as minor. 
Major Vascular Complications 
Hemorrhagic vascular complications included the following: 
• Haematoma at access site >5 cm 
• False aneurysm 
• AV fistula 
• Retroperitoneal bleed 
• Peripheral ischemia/nerve injury 

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• Any transfusion required will be reported as a vascular complication unless clinical 
indication clearly other than catheterization complication 
• Vascular surgical repair 
Patent Run-off 
At least one patent native outflow artery from the popliteal to the ankle, free from significant 
(≥50%) stenosis as confirmed by angiography or ultrasound that has not previously been 
revascularized. 
 
Per-Protocol (PP) 
The PP analysis is based on all subjects that are characterized by appropriate exposure to treatment 
(procedurally correct as pre-specified), availability of measurements, and the absence of major 
protocol violations including violations of entry criteria. 
 
Primary Patency 
Primary Patency of the target lesion is defined as the absence of binary restenosis based on DUS 
peak systolic velocity ratio ≥2.5 (or based on angiography if performed), as analyzed by 
independent core lab, without prior target lesion revascularization. (Alternative Primary Patency is 
also reported PSVR thresholds ≥2.0 and ≥3.0.) 
Procedural success 
Attainment of ≤30% residual stenosis in the treatment area by independent core lab analysis 
without major adverse events during the index procedure. 
 
Popliteal Artery 
The vessel located between Hunter’s canal and the trifurcation. 
 
PSVR 
Peak Systolic Velocity Ratio 
 
Reference Vessel Diameter (RVD) 
The interpolated reference vessel diameter is based on a computed estimation of the original 
diameter of the artery at the level of the obstruction (minimal luminal diameter) 
 
Restenosis 
Either ≥50% restenosis of the diameter of the reference-vessel segment by QVA or peak systolic 
velocity ratio of ≥2.5, determined by blinded ultrasound and independent core lab analysis. 
Restenotic Lesion 
A lesion in a vessel segment that had undergone a prior percutaneous treatment 

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Rutherford Categories 
 
Grade Category Clinical Description 
Objective Criteria 
0 
Asymptomatic, no 
hemodynamically significant 
occlusive disease 
Normal results of treadmill (5 min,2 mph, 
12⁰ constant grade) 
I 
1 
Mild Claudication 
Treadmill exercise complete, post exercise 
AP is greater than 50 mm Hg but more 
than 25 mm Hg less than normal 
2 
Moderate Claudication 
Symptoms between categories 1 and 3 
3 
Severe Claudication 
Treadmill exercise cannot be completed 
post exercise AP is less than 50 mm Hg 
II 
4 
Ischemic rest pain 
Resting AP of 40 mm Hg or less, flat or 
barely pulsatile ankle or metatarsal 
plethysmographic tracing, toe pressure less 
than 30 mm Hg 
III 
5 
6 
Minor tissue loss, non-healing ulcer, 
or focal gangrene with diffuse pedal 
ischemia 
Resting AP of 60 mm Hg or less, flat or 
barely pulsatile ankle metatarsal 
plethysmographic tracing flat or barely 
pulsatile, toe pressure less than 40 mm Hg 
Major tissue loss, extending above 
transmetatarsal level, functional foot 
no longer salvageable 
Same as category 5 
 
Screen Failures 
Subjects screened, but not meeting all study entry criteria and hence are not enrolled, are 
considered screening failures and will be documented as such on the Screening Logs. 
Secondary Patency 
Secondary Patency of the target lesion is defined as the absence of binary restenosis based on DUS 
peak systolic velocity ratio ≥2.5 (or based on angiography if performed) as analyzed by 
independent core lab, independent of whether or not patency is re-established via an endovascular 
procedure. 
 
Stroke 
Clinical signs/symptoms of focal neurological deficit lasting longer than 24 hours. 
 
Target Lesion 
Lesion that is to be treated during the index procedure. For study inclusion, the lesion must be ≥1 cm 
below the common femoral bifurcation and terminates distally ≤2 cm below the tibial plateau AND ≥1 
cm above the origin of the posterior tibial trunk, with the intent of staying above the trifurcation. 

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Target Lesion Revascularization 
A repeat revascularization procedure (percutaneous or surgical) of the original target lesion site. 
 
Target Vessel Revascularization 
A repeat revascularization procedure (percutaneous or surgical) of a lesion in the target vessel. 
 
Target Vessel 
The entire vessel in which the target lesion is located. 
 
Technical Success 
Technical Success of the balloon procedure is defined as successful access and deployment of the 
device and visual estimate of ≤30% diameter residual stenosis during the index procedure without 
deployment of a bailout stent. 
Treatment Area 
The entire treated vessel segment in which angioplasty balloons were inflated (the injury segment) 
including the target lesion. 
Thrombosis 
A total occlusion documented by duplex ultrasound and/or angiography at the treatment site with 
or without symptoms Thrombosis may be categorized as acute (<1 day), subacute (1-30 days) and 
late(>30 days). The presence of thrombus at the target lesion must be noted as an adverse event in the 
eCRF. 
 
Transient Ischemic Attack (TIA) 
Clinical signs/symptoms of focal neurological deficit lasting up to 24 hours 
 
Walking Impairment Questionnaire (WIQ) 
A measure of subject-perceived walking performance for subjects with PAD and/or intermittent 
claudication. This questionnaire estimates walking distance, walking speed and stair climbing 
capacity. 
Worsening of Ankle Brachial Index 
A deterioration in the Ankle Brachial Index (ABI) by more than 0.15 from the maximum early 
post-procedural level. 
Worsening Rutherford Clinical Category 
A deterioration (an increase) in the Rutherford Category by more than 1 category from the earliest 
post-procedural measurement. 
 
(APPENDICES B-F PURPOSELY REDACTED)