A Prospective, Multicenter, Single Blind, Randomized, Controlled Trial Comparing the Moxy Drug Coated Balloon vs. Standard Balloon Angioplasty for Treatment of Femoropopliteal Arteries
Phase: NA
Conditions: Femoral Artery Stenosis, Popliteal Artery Stenosis, Femoral Artery Occlusion, Popliteal Artery Occlusion
Sponsor: C. R. Bard

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  A Prospective, Multicenter, Single Blind, Randomized, 
Controlled Trial Comparing the Moxy™ Drug Coated Balloon 
vs. Standard Balloon Angioplasty for Treatment of  
Femoropopliteal Arteries 
 
 
 
Investigational Plan  
Version 8.0 
 
 
Sponsor: 
 
 
 
9409 Science Center Drive 
Ne Hope, MN 55428 USA 
 
 
Investigational Device: Moxy™ Drug Coated Balloon 
 
NCT Number: 01412541* 
*NCT 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 Trial Investigational Plan 
A Prospective, Multicenter, Single Blind, Randomized, Controlled Trial Comparing the 
Moxy™ Drug Coated Balloon vs. Standard Balloon Angioplasty 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 Lutonix LEVANT 2 Trial Protocol Summary 
Title 
A Prospective, Multicenter, Single Blind, Randomized, Controlled Trial 
Comparing the Moxy™ Drug Coated Balloon vs. Standard Balloon Angioplasty 
for Treatment of Femoropopliteal Arteries  (LEVANT 2) 
Test Device 
Moxy™ Drug Coated Balloon 
Control Device 
Non-coated standard percutaneous transluminal angioplasty balloon catheter 
(standard PTA catheter) 
Study Design 
Prospective, Multicenter, Single Blind, Randomized, Safety and Efficacy 
Overview 
The study will enroll patients 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 determined not to require stenting based on 
defined angiographic criteria are randomized 2:1 to treatment with either the 
Moxy Drug Coated Balloon (test arm) or standard PTA catheter (control arm). 
Subjects that do not meet post-predilatation lesion criteria are excluded (and 
treated per standard practice) and followed for safety for 30 days.  
Randomized subjects will have ultrasound and clinical follow-up through 2 
years and telephone follow-up through 5 years. An Economic Assessment sub-
study (AMORE) will be conducted at sites in the USA. 
Purpose 
To assess the safety and efficacy of the Moxy Drug Coated Balloon for 
treatment of stenosis or occlusion of the femoral and popliteal arteries 
Objective 
To demonstrate the superior efficacy and non-inferior safety of the Moxy Drug 
Coated Balloon by direct comparison to standard PTA catheter for treatment of 
stenosis of the femoropopliteal arteries 
Randomization Subjects will be randomized 2:1 to Moxy Drug Coated Balloon or standard 
PTA catheter 
Enrollment 
Enrollment will occur at up to 55 global centers. 
 
Approximately 750 subjects will be enrolled in order to include a total of 476 
randomized subjects.  Enrollment will be stopped once 476 subjects are 
randomized.  An additional 55 roll-in subjects may be included for site training 
purposes. 
 
Approximately 50% of randomized enrollment will be in the USA. 
Randomized 
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 
Endpoints 
Safety 
Composite of freedom from all-cause peri-operative (≤30 day) death and 
freedom at 1 year from the following: index limb amputation (above or below 
the ankle), index limb re-intervention, and index-limb-related death. 
 
 

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Efficacy 
Primary Patency of the target lesion at 1 year. 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). 
Secondary 
Endpoints 
Efficacy 
• Acute Device, Technical and Procedural success  
   
 The following endpoints will be assessed at 6, 12 and 24 Months: 
• Primary and Secondary Patency (DUS PSVR <2.5) 
• 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 
• Change in Walking Impairment Questionnaire from baseline 
• Change in Six Minute Walk Test from baseline in a subset of 
patients 
• Change in quality of life from baseline, as measured by EQ-5D and 
SF36-v2 surveys 
Safety 
• Freedom at 30 days from all-cause death, index limb amputation 
above the ankle and target vessel revascularization (TVR) (VIVA 
Safety Endpoint)  
• Composite of freedom from all-cause perioperative (≤30 day) death 
and freedom from the following at 1, 6, 24, 36, 48, and 60 months: 
index limb amputation, index limb re-intervention, and index-limb-
related death. 
The following endpoints will be assessed at 1, 6, 12, 24, 36, 48 and 60 
months: 
• 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 

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• Readmission for cardiovascular events  
Other 
• Target limb related hospital days at 1 and 2 years 

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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 
Intent-to-treat (ITT) composite dataset including all randomized subjects. 
Secondary as-treated and per-protocol analyses will also be performed. 

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Principal 
Investigators 
Dr. Kenneth Rosenfield (USA)     
Massachusetts General Hospital 
55 Fruit Street 
Boston, MA 02114 USA 
617-724-1935 
 
Prof. Dr. Dierk Scheinert (EU)    
Park Krankenhaus 
Strümpellstraße 41 
04289 Leipzig, Germany 
+49-0341 864-0  
Sponsor/ 
Contact: 
Lutonix, Inc. 
Dr. Sharon McFadden 
9409 Science Center Drive 
New Hope, MN 55428 USA 
763-445-2352 
US CRO 
Prairie Education and Research Cooperative 
317 N 5th Street 
Springfield, IL 62701 USA 
217-492-9104 
EU CRO 
genae associates nv 
Head office: Paleisstraat 24 
CRO: Lange Lozanastraat 112 
2018 Antwerp, Belgium 
+32 3 290 03 06  
Electronic Data 
Capture (EDC) 
MedNet Solutions, Inc. 
110 Cheshire Lane, Suite 300 
Minnetonka, MN 55305 USA 
763-258-2735 - Main 
Angiographic 
Core Lab 
SynvaCor 
319 N. 5th St. 
Springfield IL 62701 USA 
217-492-9132 
DUS Core Lab 
VasCore 
62 Staniford St 
Boston MA 02114 USA 
617-726-5552 
Pharmacokinetic 
Core Lab 
BASi 
2701 Kent Ave 
W Lafayette, IN 47906 
EU Authorized 
Representative: 
BARD Limited 
Crawley 
RH11 9BP 
United Kingdom 
 

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Table of Contents 
1 
INTRODUCTION ...................................................................................................................... 13 
1.1 
CLINICAL BACKGROUND ...................................................................................................... 13 
1.2 
DEVICE AND STUDY RATIONALE ........................................................................................ 17 
2 
STUDY OBJECTIVES AND ENDPOINTS ............................................................................ 17 
2.1 
PRIMARY OBJECTIVE .............................................................................................................. 18 
2.2 
PRIMARY ENDPOINTS ............................................................................................................. 18 
2.3 
SECONDARY ENDPOINTS....................................................................................................... 18 
3 
DEVICE DESCRIPTION .......................................................................................................... 19 
3.1 
INTENDED USE / INDICATIONS FOR USE ........................................................................... 20 
3.2 
ACTIVE PHARMACEUTICAL INGREDIENT (API): PACLITAXEL .................................... 20 
3.3 
EXCIPIENT (Drug Carrier) ......................................................................................................... 20 
3.4 
DEVICE INSTRUCTIONS .......................................................................................................... 20 
3.5 
SUPPLY & SUPPORT OF INVESTIGATIONAL DEVICE ...................................................... 20 
4 
RISK-BENEFIT ANALYSIS .................................................................................................... 21 
4.1 
POTENTIAL RISKS .................................................................................................................... 21 
4.2 
RISK MANAGEMENT PROCEDURES .................................................................................... 23 
4.3 
POTENTIAL BENEFITS............................................................................................................. 24 
4.4 
EARLY TERMINATION ............................................................................................................ 24 
5 
CLINICAL STUDY DESIGN ................................................................................................... 25 
5.1 
SCREENING PROCEDURES ..................................................................................................... 26 
5.2 
PATIENT SELECTION FOR ENROLLMENT .......................................................................... 27 
5.3 
SUBJECT INCLUSION AND EXCLUSION CRITERIA .......................................................... 28 
6 
STUDY/TREATMENT PROCEDURES ................................................................................. 30 
6.1 
ENROLLMENT ........................................................................................................................... 30 
6.2 
MOXY DRUG COATED BALLOON INSTRUCTIONS FOR USE (IFU) ............................... 30 
6.3 
BASELINE ANGIOGRAM ......................................................................................................... 31 
6.4 
IN-FLOW LESION TREATMENT ............................................................................................. 31 
6.5 
PRE-DILATATION ..................................................................................................................... 31 
6.6 
RANDOMIZATION .................................................................................................................... 32 
6.7 
POST TREATMENT AND PROVISIONAL (BAILOUT) STENTING PROCEDURES ......... 32 
6.8 
UNSCHEDULED ANGIOGRAPHY/REVASCULARIZATION .............................................. 34 
7 
TREATMENT OF SUBJECT ................................................................................................... 34 
7.1 
BLINDING PLAN ....................................................................................................................... 35 
7.2 
MEDICATIONS ........................................................................................................................... 35 
7.3 
STANDARD TESTS, PROCEDURES, AND FOLLOW-UP ..................................................... 37 
8 
ADVERSE EVENTS .................................................................................................................. 40 

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8.1 
ADVERSE EVENT REPORTING .............................................................................................. 40 
9 
SUBJECT WITHDRAWAL CRITERIA ................................................................................ 40 
10 
DATA COLLECTION AND MONITORING ........................................................................ 41 
10.1 
DATA COLLECTION ................................................................................................................. 41 
10.2 
MONITORING ............................................................................................................................ 41 
10.3 
SOURCE DOCUMENTATION .................................................................................................. 43 
10.4 
RECORD RETENTION............................................................................................................... 43 
10.5 
STUDY PROCESSING ............................................................................................................... 44 
11 
DEVICE ACCOUNTABILITY ................................................................................................ 44 
11.1 
SUPPLY AND SUPPORT OF INVESTIGATIONAL DEVICE ................................................ 45 
12 
STUDY MANAGEMENT ......................................................................................................... 45 
12.1 
STEERING COMMITTEE .......................................................................................................... 45 
12.2 
DATA MONITORING COMMITTEE ........................................................................................ 46 
12.3 
CLINICAL EVENTS COMMITTEE .......................................................................................... 46 
13 
REGULATORY RESPONSIBILITIES ................................................................................... 46 
13.1 
IRB/EC APPROVAL ................................................................................................................... 46 
13.2 
REGULATORY APPROVAL ..................................................................................................... 47 
13.3 
INFORMED CONSENT .............................................................................................................. 47 
13.4 
SELECTION OF CLINICAL SITES AND INVESTIGATORS ................................................. 47 
13.5 
INVESTIGATOR’S RESPONSIBILITIES ................................................................................. 48 
13.6 
LUTONIX RESPONSIBILITIES ................................................................................................ 49 
14 
PUBLICATIONS ....................................................................................................................... 50 
15 
STATISTICAL ANALYSIS PLAN .......................................................................................... 50 
15.1 
OVERVIEW OF STUDY DESIGN ............................................................................................. 50 
15.2 
ASSESSMENT OF COMPARABILITY OF TREATMENT GROUPS AND POOLABILITY 
OF SITES AND SECONDARY ANALYSES .......................................................................................... 51 
15.3 
HANDLING OF MISSING DATA ............................................................................................. 52 
15.4 
PRIMARY ENDPOINTS ............................................................................................................. 53 
15.5 
SECONDARY ENDPOINTS....................................................................................................... 58 
APPENDIX A:  DEFINITIONS ........................................................................................................ 64 
APPENDIX B:  DRAFT CASE REPORT FORM ELEMENTS ........ ERROR! BOOKMARK NOT 
DEFINED. 
APPENDIX C:  SIX MINUTE WALK TEST GUIDELINESERROR! BOOKMARK NOT DEFINED. 
APPENDIX D:  WALKING IMPAIRMENT QUESTIONNAIRE .... ERROR! BOOKMARK NOT 
DEFINED. 
APPENDIX E:  SF36V2 QUESTIONNAIRE ................... ERROR! BOOKMARK NOT DEFINED. 

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APPENDIX F:  EQ5D QUESTIONNAIRE ....................... ERROR! BOOKMARK NOT DEFINED. 
APPENDIX G:  SAMPLE INSTRUCTIONS FOR USE . ERROR! BOOKMARK NOT DEFINED. 
APPENDIX H: SAMPLE INFORMED CONSENT FORMSERROR! BOOKMARK NOT DEFINED. 
APPENDIX I:  ANGIOGRAPHIC ACQUISITION GUIDELINES . ERROR! BOOKMARK NOT 
DEFINED. 
APPENDIX J: DUPLEX ULTRASOUND CORE LAB GUIDELINESERROR! BOOKMARK NOT 
DEFINED. 
APPENDIX K: ECONOMIC SUB STUDY PROTOCOL (AMORE)ERROR! BOOKMARK NOT 
DEFINED. 
APPENDIX L: SPONSOR-QUALIFIED INVESTIGATIONAL SITESERROR! BOOKMARK NOT 
DEFINED. 
APPENDIX M: LEVANT 2 CONTINUED ACCESS REGISTRY ... ERROR! BOOKMARK NOT 
DEFINED. 
 
Tables 
Table 1: THUNDER and FemPac Results ..................................................................................................... 15 
Table 2: LEVANT I Trial Primary Analysis at 6 Months, ITT ..................................................................... 16 
Table 3: LEVANT I Results by Stratification Groups at 6 months ............................................................... 16 
Table 4: Device Matrix, Moxy Drug Coated Balloon.................................................................................... 21 
Table 5: Post Pre-Dilatation Lesion(s) Criteria .............................................................................................. 32 
Table 6: Provisional (Bailout) Criteria........................................................................................................... 33 
Table 7: Medication Schedule........................................................................................................................ 36 
Table 8: Follow-Up Schedule and Testing Requirements for Randomized Subjects .................................... 37 
Table 9: Schedule of PK Sampling ................................................................................................................ 39 
Table 10: Reports Required From Clinical Investigators .............................................................................. 49 
Table 11: Historic Data for Primary Safety Endpoint Estimation ................................................................. 54 
Table 12: Historic Data for Primary Efficacy Endpoint Estimation .............................................................. 56 
 
 
Figures 
Figure 1:  Moxy Drug Coated Balloon .......................................................................................................... 19 
Figure 2 : Chemical Structure of Paclitaxel ................................................................................................... 20 
Figure 3: Study Flowchart ............................................................................................................................. 26 
Figure 4: Allowed Lesion Location ............................................................................................................... 28 
 
 
 

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1 INTRODUCTION 
The purpose of this investigation is to assess the safety and efficacy of the Moxy™ Drug Coated 
Balloon for treatment of a stenosis or occlusion of the femoropopliteal arteries. 
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 Moxy 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, 
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, 
 
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. 
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. 

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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 Moxy Drug Coated Balloon, is one example of a DCB.  
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 
 
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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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.   
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 
Moxy 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 Moxy Drug Coated Balloon or a standard 
PTA catheter (control group).  Subject inclusion and exclusion criteria were similar to previous 
 
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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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.  The Moxy Drug Coated Balloon showed safety at 30 days compared 
to control with no unanticipated adverse device effects, similar adverse event rates and no reports 
of thrombus in the DCB arm.  
At 6 months, clinical follow up compliance was 91%, and 74% and subjects underwent protocol 
defined repeat angiography.  Major 6-month angiographic and clinical endpoint results are listed in 
Table 2 for the intent-to-treat (ITT) population (n=101) and in Table 3 by stratification group.  
TABLE 2: LEVANT I TRIAL PRIMARY ANALYSIS AT 6 MONTHS, ITT 
Angiographic  
Moxy Drug Coated Balloon 
PTA 
Primary Endpoint, n ±SD 
-  Late Lumen Loss  (p = 0.016) 
 
0.46 ±1.13 
 
1.09 ±1.07 
Binary Restenosis, n/N (%) 
11/39 (28) 
18/35 (50) 
Clinical  
Moxy Drug Coated Balloon 
PTA 
TLR, n/N (%) 
6/47 (12.8) 
10/45 (22.2) 
TVR, n/N (%) 
6/47 (12.8) 
15/46 (32.6) 
Thrombosis, n/N (%) 
0/49 (0) 
2/52 (4) 
Amputation , n/N (%) 
1/49 (2)* 
0/52 (0) 
Death, n/N (%) 
1/49 (2)* 
3/52 (6) 
                 *Amputation and Death in same subject. Formally adjudicated as not device or procedurally related. 
TABLE 3: LEVANT I RESULTS BY STRATIFICATION GROUPS AT 6 MONTHS 
Angiographic 
Balloon-Only Strata 
Stent Strata 
Moxy 
PTA 
Moxy 
PTA 
Late Lumen Loss, n ±SD  
0.45 ±1.18 
1.19 ±1.15 
0.49 ±1.01 
0.90 ±0.91 
Binary Restenosis, n/N (%) 
9/31 (29) 
14/24 (58) 
2/8 (25) 
4/11 (36) 
Clinical  
Moxy 
PTA 
Moxy 
PTA 
TLR, n/N (%) 
5/36 (13.9) 
7/33 (21.2) 
1/11 (9.1) 
3/13 (23.1) 
TVR, n/N (%) 
5/36 (13.9) 
9/33 (27.3) 
1/11 (9.1) 
6/13 (46.2) 
 
In the ITT population, the primary endpoint of mean late lumen loss at 6 months was significantly 
lower in the Moxy Drug Coated Balloon arm (0.46±1.13) compared to the PTA arm (1.09±1.07), 
with a p value of 0.016, consistent with efficacy of Moxy Drug Coated Balloon for this indication.  
The difference in mean late loss between arms was also significant in the balloon-only 
stratification group (0.45±1.18 vs. 1.19±1.15, p=0.024).  
The Moxy Drug Coated Balloon demonstrated safety comparable to conventional PTA in the 
LEVANT I Trial, with similar AE and SAE rates through 6 months. There were no unanticipated 

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adverse device effects in the drug-coated balloon arm, and overall adverse event rates were similar 
to conventional uncoated balloon angioplasty. Secondary clinical endpoints trended in favor of the 
Moxy Drug Coated Balloon arm, particularly TLR (12.8% vs. 22.2% in PTA arm) and target 
vessel revascularization (TVR) (12.8% vs. 32.6%).  
As part of a pharmacokinetics sub-study, serum paclitaxel levels were collected and analyzed in 7 
Moxy Drug Coated Balloon subjects.  All subjects had detectable serum paclitaxel immediately 
after the index procedure, with a mean maximum concentration Cmax = 58.4±83.2 ng/mL.  Mean 
total exposure AUCall = 73.2±45.3 ng*h/mL. The mean residence time (from index procedure to 
the last measurable concentration) of paclitaxel in serum MRTlast = 5.64±4.56 hours. 
In summary, 6-month results demonstrated the feasibility, safety, and efficacy of the use of the 
Moxy Drug Coated Balloon for treatment of femoropopliteal lesions, with a significantly improved 
late lumen loss and similar adverse events rates as compared to PTA through 6-months.   
1.2 DEVICE AND STUDY RATIONALE 
The Moxy 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 Moxy 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 Moxy 
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 Moxy 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 Moxy Drug Coated Balloon. 
2 STUDY OBJECTIVES AND ENDPOINTS 
Data from all subjects will be analyzed on an ITT basis regardless of final treatment disposition, 
device success or procedural success. 
 
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 Clinical Study is to demonstrate superior efficacy and 
non-inferior safety at one year of the Moxy Drug Coated Balloon by direct comparison to a 
standard PTA catheter for treatment of stenosis or occlusion of the femoropopliteal arteries.  
2.2 PRIMARY ENDPOINTS 
2.2.1 SAFETY 
The primary safety endpoint is the composite of freedom from all-cause perioperative (≤30 day) 
death and freedom at 1 year from the following: index limb amputation (above or below the ankle), 
index limb re-intervention, and index-limb-related death. 
2.2.2 EFFICACY 
The primary efficacy endpoint is primary patency of the target lesion at 1 year. Primary patency is 
defined as the absence of target lesion restenosis (defined by Duplex Ultrasound Peak Systolic 
Velocity Ratio (DUS PSVR) ≥2.5) and freedom from TLR. 
2.3 SECONDARY ENDPOINTS 
The following endpoints will be reported using descriptive statistics in the final Study Report. 
Efficacy 
• 
Acute Device, Technical and Procedural success  
   The following endpoints will be assessed at 6, 12 and 24 Months: 
• 
Primary and Secondary Patency (DUS PSVR <2.5) 
• 
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 ABI from baseline 
• 
Change in Walking Impairment Questionnaire from baseline  
• 
Change in Six Minute Walk Test from baseline in a subset of patients 
• 
Change in quality of life from baseline, as measured by EQ-5D and SF36-v2 surveys 
Safety 
• Freedom at 30 days from all-cause death, index limb amputation above the ankle and 
TVR (VIVA Safety Endpoint)  

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• Composite of freedom from all-cause perioperative (≤30 day) death and freedom from 
the following at 1, 6, 24, 36, 48, and 60 months: index limb amputation, index limb re-
intervention, and index-limb-related death. 
The following endpoints will be assessed at 1, 6, 12, 24, 36, 48 and 60 months: 
• 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  
Other 
• 
Target limb related hospital days at 1 and 2 years 
The primary analysis is ITT, including all randomized subjects.  Secondary as-treated and per-
protocol analyses will also be performed. 
3 DEVICE DESCRIPTION  
The Moxy Drug Coated Balloon is a standard PTA catheter with a drug coating on the balloon 
portion of the catheter.  The Moxy 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:  MOXY 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. 

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3.1 INTENDED USE / INDICATIONS FOR USE 
The Moxy 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. 
 
 
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 G.  
3.5 SUPPLY & SUPPORT OF INVESTIGATIONAL DEVICE  
An investigational device supply of the Moxy 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 4.  Always confirm current site inventory supply prior to enrolling subjects into the 
study.   

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TABLE 4: DEVICE MATRIX, MOXY 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.  Each study site will receive a supply of the Moxy 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, 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 Moxy 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 Moxy 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 Moxy 
Drug Coated Balloon that are unknown at this time.  Please refer to the Investigator’s Brochure for 
more details on the development of the Moxy 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 

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• 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 
• 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.  

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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 
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 Moxy 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 
Moxy 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 Moxy Drug Coated Balloon to 
help mitigate any risks to the subjects due to product failure.  Additionally, animal studies using 

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the Moxy 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 Moxy 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 Moxy Drug Coated Balloon are not known at the present time. Alternatives to the use of 
the Moxy 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 Moxy Drug Coated 
Balloon is extremely low, and the potential benefits of decreased restenosis and 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 Data Monitoring Committee (DMC) 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 
• Inability to meet enrollment targets (1.5 subjects/month) 
• 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 

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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) are randomized 2:1 to treatment with either the Moxy Drug 
Coated Balloon (test arm) or standard PTA catheter (control arm).   
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.  Randomized 
subjects will have ultrasound and clinical follow-up through 2 years and telephone follow-up 
through 5 years. There is no pre-set limit to site enrollment, however site enrollment will be 
tracked and managed to ensure approximately 50% of the overall randomized enrollment occurs at 
US sites.  
 
 
 
 
 
 
 
 
 
 
 
 
 

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Figure 3 contains an overview of the study.  
Post-Predilatation Lesion Criteria
Baseline Angiogram
Test Arm
Dilatation with Drug 
Coated Balloon
Control Arm
Dilatation with uncoated 
balloon
Defined Pre-Dilatation
(Balloon inflated to ~1mm <RVD)/
Enrollment
Randomization
2:1
Defined bailout stenting
(if necessary) with FDA approved Stent. 
Standard Post-Dilatation per physician 
discretion.
Subjects followed for 
Safety through 30 days 
and withdrawn
Recruitment
Major Flow Limiting Dissection
-OR- 
Residual Stenosis >70%
Residual Stenosis ≤70% and Absence of Flow-Limiting 
Dissection
-OR-
Lesion is not appropriate for stenting due to proximity to 
the knee joint
Treat per Standard Practice or
No additional Treatment required
 
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 CMP  
▪ Glucose 
▪ Calcium 
▪ Protein (albumin, TP) 
▪ Electrolytes (bicarbonate, chloride, sodium, potassium) 
▪ Kidney (BUN, creatinine) 
▪ Liver (ALP, ALT, AST, bilirubin)  
o Pregnancy Test (blood or urine; if female of child bearing potential) 
• Resting Ankle-Brachial Index (ABI) (within 90 days) 
• Walking Impairment Questionnaire 
• EQ5D and SF-36-v2 Questionnaires 
• Six Minute Walk Test  
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 ROLL-IN SUBJECTS AND CASE PROCTORING REQUIREMENTS 
After site initiation, each site must perform a proctored Moxy Drug Coated Balloon procedure 
prior to enrolling subjects in the randomized portion of the trial.  This is intended to train site 

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personnel in proper procedure and data collection.  All roll-in subjects must meet all protocol 
requirements (including enrollment criteria and follow-up) and the sponsor (or designee) must be 
in attendance for training purposes.  A subject(s) who was proactively designated as a roll-in, but 
subsequently treated per the standard practice arm (i.e. not treated with the Moxy Drug Coated 
Balloon) is not considered a roll-in. The roll-in subjects will be analyzed separately from the 
randomized cohort.  Based on a total of 55 sites, a maximum of 55 of roll-in subjects is expected.  
Some centers may have more than one investigator performing the study procedure; each 
investigator enrolling in the study must undergo formal Moxy procedure proctoring with a sponsor 
representative (or designee) during their initial study 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. 
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 
 
≥1 cm below 
bifurcation 
≤2 cm below t. plateau  
&  
≥1 cm above TP  

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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. 
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; 

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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 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. 
All subjects enrolled and randomized in the trial will be followed for the entire duration of the 
study and included in the ITT analysis. Subjects that do not meet post-predilation criteria are 
enrolled, but not randomized, and 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 randomized in the study. 
6.2 MOXY DRUG COATED BALLOON INSTRUCTIONS FOR USE (IFU) 
Always follow the current IFU packaged with the device for procedural information, preparation 
and use of the Moxy 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 Moxy 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 

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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 
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 Moxy Drug Coated Balloon for complete pre-
dilatation requirements. 
Lesion(s) pre-dilatation(s) is required for all (test and control) 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 Moxy 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 5 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 randomized but is 
instead treated per institutional standard practice.  Nonrandomized subjects excluded after pre-
dilatation will be followed for 30 days for safety and then withdrawn. 
 
 
 
 
 
 

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TABLE 5: POST PRE-DILATATION LESION(S) CRITERIA 
Angiographic Condition 
Treatment 
Major Flow Limiting Dissection 
-OR- 
Residual Stenosis >70% 
 
Excluded, not randomized, 
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 
Randomized 2:1 to Test 
(Moxy Drug Coated 
Balloon) or Control 
(standard PTA catheter) 
 
6.6 RANDOMIZATION 
If after pre-dilatation(s), patients are determined to meet the criteria for randomization, they will be 
randomized using a pre-specified site randomization system. Subjects will be randomized in a 2:1 
fashion to Test (Moxy Drug Coated Balloon) or Control (standard PTA catheter), see  
Figure 3.     
6.6.1 TREATMENT WITH STANDARD PTA CATHETER (CONTROL) 
For subjects randomized to the control arm, a treatment with an uncoated standard PTA catheter 
will be performed following the Investigator’s standard procedure for such a treatment and 
utilizing a locally approved, standard off-the-shelf PTA balloon. Use of embolic capture 
angioplasty balloons or cutting/scoring balloons is not allowed. 
The Investigator should determine the appropriate size of the balloon to be used by visual 
assessment. The Investigator should use an uncoated balloon of similar length and diameter to the 
Moxy Drug Coated Balloon to ensure similarity of treatment between test and control arms. 
6.6.2 TREATMENT WITH MOXY DRUG COATED BALLOON (TEST) 
Please refer to the current Moxy 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 Moxy 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.  This discrepancy is likely attributable 
to investigator bias that the control arm is less likely to succeed and thus the threshold for stenting 

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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; imbalance in bailout 
stenting between treatment arms could influence the outcome of the study.  Due to the importance 
of equal treatment between test and control groups, plus 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 6) 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 6: 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 
>10mmHg (pressure wire) measured immediately distal to the target lesion 
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. 

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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.  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.  
 
 
 
 
 
 
 
 
 
 
 
 
 

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7.1 BLINDING PLAN 
In order to minimize the introduction of bias into the study, a pre-specified blinding plan has been 
developed.  All Duplex Ultrasound operators, core lab evaluators, and members of the Clinical 
Events Committee (CEC) will be blinded to the subject’s treatment assignment.  Both the subject 
as well as the investigator conducting the follow-up visit will be blinded to treatment until the 
completion of the 12 month visit. Blinding procedures will be reviewed at the time of each site 
initiation by a sponsor representative.  Blinding procedures and instructions are as follows: 
Time point 
Blinding Procedure 
Informed Consent/ 
Pre-Procedure 
During review of the study and the informed consent process with the patient, 
blinding procedures, timelines and rationale should be discussed with the 
subject and any care takers. 
Randomization 
Communication to the Investigator performing the procedure as to the 
randomized treatment should be done in such a way as to prevent the subject 
from overhearing which group they have been allocated to. Hand signals, 
written codes, scripts or headphones can all be employed to ensure the subject 
remains blinded.  Each site must develop a system that best works with lab 
work flow.  
Post-Procedure 
It is important that recovery and hospital/clinic staff is educated to the protocol 
blinding requirements and that the subject and care taker are not inadvertently 
unblinded during the recovery period.  In addition, the medical record should 
clearly identify the subject as a study participant and the type of treatment 
should be kept confidential. 
Follow-up 
The one month (if clinical visit), 6 and 12 month follow-up visits must be 
performed by a blinded site investigator.  If only a single interventional 
investigator exists at any one site, an additional site sub-investigator qualified 
to conduct follow up assessments for this population (physician, nurse 
practitioner, physician assistant, etc.)  should be appointed to conduct the 
blinded study related follow-up visits prior to any standard follow up, if 
applicable, with the interventional investigator.  The clinical status of the 
subject (for assessment of clinical and primary safety endpoints) should be 
established prior to performing the required DUS (for assessment of the 
primary efficacy endpoint). 
Unblinding 
A subject may not become unblinded prior to the completion of the 12 month 
follow up unless it should become medically necessary as determined by the 
investigator.   
7.2 MEDICATIONS 
Table 7 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 

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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 
(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 7: MEDICATION SCHEDULE 
Drug 
Pre-Procedure 
Procedure 
Post-Procedure* 
Aspirin 
75-325 mg/day 
NA 
75-100 mg/day indefinitely 
Clopidogrel 
 
OR 
 
Prasugrel*** 
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** 
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 neither Clopidogrel nor Prasugel are appropriate  
7.2.1 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) or prasugrel (10 mg per 
day) be prescribed. The initial loading dose of clopidogrel or prasugrel 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. 
7.2.2 INTRA-PROCEDURE 
All subjects must receive adequate anticoagulation according to hospital standard practice.  
7.2.3 POST-PROCEDURE 
Approved vascular closure devices are allowed.  Clopidogrel (75 mg/daily) or prasugrel (5-10 
mg/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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7.3 STANDARD TESTS, PROCEDURES, AND FOLLOW-UP 
Table 8 displays the required schedule for randomized 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, but not randomized, 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 8: Follow-Up Schedule and Testing Requirements for Randomized Subjects 
 
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 
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  
mont
h 
±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; CMP, pregnancy6) 
 
√5 
 
√ 
√3 
√ 
√ 
 
 
 
 
Six minute Walk Test7 
 
√ 
 
 
 
√ 
√ 
√ 
 
 
 
WIQ, EQ5D and  
SF36-v2 Questionnaires 
 
√ 
 
 
 
√ 
√ 
√ 
 
 
 
Angiogram 
 
 
√ 
 
 
 
 
 
 
 
 
Adverse Event Monitoring 
 
 
√ √ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Duplex Ultrasound (after 
clinical assessment) 
 
 
 
√8 
√ 
√ 
√ 
 
 
 
PK Study9 
 
√ 
 
√ 
√ 
 
 
 
 
 
 

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7Unless physical condition precludes from testing 
8Baseline duplex is only required once (anytime post-procedure through the 1-month visit) 
9A subset of approximately 30 subjects at select USA sites 
 
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).  
 
7.3.1 TESTING 
7.3.1.1  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) 
• CMP 
o Glucose 
o Calcium 
o Protein (HSA, TP) 
o Electrolytes (bicarbonate, chloride, sodium, potassium) 
o Kidney (BUN, creatinine) 
o Liver (ALP, ALT, AST, bilirubin) 
• Pregnancy Test (blood or urine; if female of child bearing potential) 
7.3.1.2 PHARMACOKINETIC TESTING 
In a subset of approximately 30 subjects treated with the Moxy Drug Coated Balloon at selected 
sites in the USA, small amounts of blood (2 vials per sample) will be collected for 
pharmacokinetic (PK) testing (blood paclitaxel level analysis) during the index hospitalization and 
at the study required 1 month follow-up visit.  Blood collection will occur at the time points shown 
in Table 9.  Efforts should be made to include only those subjects who will be available to provide 
all scheduled samples.  Detailed PK collection instructions and materials will be provided to select 
sites by the PK core laboratory.  These subjects may have a 4F venous sheath inserted at the time 
of procedure and left in situ until all blood tests are completed to provide for additional subject 
comfort.  Any subjects receiving a drug-eluting/coated stent within 12 months prior or during the 
index procedure cannot be included in the PK testing.  All Moxy Drug Coated Balloons used to 
treat patients undergoing PK testing will be returned to Lutonix after the procedure for analysis. 
 

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TABLE 9: SCHEDULE OF PK SAMPLING 
PK Sample 
Time Point 
1 
Pre-Procedure (baseline) 
2 
Immediately Post Procedure 
3 
1 Hour Post Procedure 
4 
3 Hours Post Procedure 
5 
Before Discharge 
6 
1 Month Clinical Follow-up Visit 
In order to maintain subject blinding and avoid unnecessary needle sticks, subjects will not be 
informed that blood drug levels are only being completed in the test arm population.  Instead, they 
will be instructed that sampling is random.  Subjects that are participating in the PK study must 
have their 1 month visit conducted as a clinical visit in order to obtain the final PK sample. 
7.3.1.3 ANKLE-BRACHIAL INDEX (ABI) 
A resting ABI must be performed per local hospital standard, and consistently among subjects over 
the lifespan of the study.   
7.3.1.4 RUTHERFORD SCALE 
Rutherford classification can be measured with or without treadmill, but must be performed 
consistently among subjects over the lifespan of the study. 
7.3.1.5 SIX MINUTE WALK TEST  
For subjects with no confounding health issues that would complicate the test (e.g. respiratory, 
cardiac, orthopedic impairments), a six minute walk test will be performed. 
See Appendix C for detailed Walk Test information. 
7.3.1.6 WALKING IMPAIRMENT QUESTIONNAIRE 
The WIQ form will be completed at pre-procedure and at 6, 12 and 24 months. 
See Appendix D for the questionnaire form. 
7.3.1.7 QUALITY OF LIFE QUESTIONNAIRES 
The EQ5D and SF36-v2 surveys will be completed at pre-procedure and at 6, 12 and 24 months. 
See Appendices E and F for the questionnaire forms. 
7.3.1.8 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 

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version of the documentation requirements.  See Appendix I and Appendix J for detailed core lab 
guidelines. 
7.3.2 FOLLOW-UP PROCEDURES 
The Investigator or Research Coordinator will contact randomized 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.    
All randomized subjects will return for follow-up at 1 (if required for duplex ultrasound), 6, 12 and 
24 months post procedure. See Table 8 for required testing at each follow-up visit time point.  
Refer to Section 7.1 Blinding Plan for specifics on maintaining the blind during the follow-up 
visits.   
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. 

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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. 
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 e- CRFs.  
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.  All 
Core Lab evaluators will be blinded to the randomized treatment.  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 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, 

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protocol compliance, informed consent process, enrolling appropriate subjects, and IRB/EC 
submissions, approvals, and continuing reviews. 
Monitoring will be performed on 100% of original medical records of all enrolled subjects for all 
case report form data fields.  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 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 
• Subject Randomization 
• 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. 

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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: 
• 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 

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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. 
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 Moxy 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 

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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. 
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 Moxy 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 Moxy 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 Data Monitoring 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.   

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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 DATA MONITORING COMMITTEE 
The Data Monitoring Committee (DMC) is responsible for the oversight and safety monitoring of 
the study. The DMC advises the Sponsor regarding the continuing safety of the trial subjects and 
those yet to be recruited to the trial, as well as the continuing validity and scientific merit of the 
trial.  The DMC members are leading experts in peripheral vascular disease, cardiovascular 
medicine and biostatistics who are not participating in the trial and have no affiliation with 
Lutonix. 
During the enrollment phase of the trial, the DMC will review accumulating safety data to monitor 
for incidence of serious vascular events that would warrant modification or termination of the trial. 
Any DMC recommendations for study modification or termination because of concerns over 
subject safety or issues relating to data monitoring or quality control will be submitted in writing to 
the Steering Committee for consideration and final decision. However, if the DMC at any time 
determines that a potential serious risk exists to subjects in this trial, the DMC chairman will 
immediately notify the Steering Committee.  
The DMC will meet at regular intervals to review the safety data. DMC responsibilities, 
membership, meeting frequencies, and procedures will be outlined in the DMC charter. 
12.3  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 
members of the CEC will be blinded to the subject’s treatment. The CEC 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/EC APPROVAL 
Investigators must submit the study protocol to their IRB/EC and obtain written approval before 
being allowed to conduct and participate in the study.  Annual re-approval must also be obtained.  

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The Investigator is also responsible for fulfilling any conditions of approval imposed by the 
IRB/EC, 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/EC and written approval obtained prior to implementation.  
13.2  REGULATORY APPROVAL 
In the USA an IDE application must be submitted to the FDA.  IDE approval must be received 
prior to the inclusion of the first US subject.  
In the EU, the study must be submitted to the Competent Authorities in each country that the study 
is being conducted, according to the national requirements. Approval or a confirmation from the 
authority that the study can start must be received prior to the inclusion of the first EU subject.  
13.3  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/EC; 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.  
13.4  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. 
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. 

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13.5  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 and approves (when necessary) the following minimum 
documents: 
• 
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 
The most recent list of Investigator names and addresses can be found in Appendix L, and will be 
updated by the Sponsor during the study as needed.   
13.5.1 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. 
13.5.2 REPORTS 
Table 10 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 10: 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 
13.6   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 LEVANT 2 pivotal trial is a global, multi-center, randomized clinical trial comparing the 
Moxy Drug Coated Balloon to standard PTA for the treatment of stenosis of the femoropopliteal 
arteries.  Approximately 750 subjects will be enrolled in order to include a total of 476 randomized 
subjects at up to 55 global centers. Enrollment will be stopped once 476 subjects are randomized.  
Subject randomization will be allocated 2:1 Moxy Drug Coated Balloon (test arm) to standard 
PTA catheter (control arm) after successful pre-dilatation.   
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, some will not meet 
criteria for randomization, and these nonrandomized patients are followed only for safety and do 
not contribute to the required evaluable sample size of 476 randomized subjects.  However, since 
the patient underwent a protocol defined predilatation, they are considered to be enrolled even 
though they are not randomized. 
The approximate number 750 of enrolled patients was estimated from the proportion of subjects in 
LEVANT I that were stratified after predilatation to stenting as well as data from other studies 
reported in the literature.  Approximately 1/3 or more of total number of predilatated subjects will 
likely not be randomized and will be treated per standard of care.  Enrollment will continue only 
until a randomized sample size of 476 is achieved, since this is the randomized sample size 
necessary for primary endpoint analysis presuming up to 15% loss-to-follow-up (i.e. 405 evaluable 
subjects). 

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Successful pre-dilatation is defined as ≤70% residual stenosis and an absence of flow-limiting 
dissection based on strict angiographic criteria.  Subjects who met these criteria are randomized.  
Subjects who do not meet post-predilitation lesion success criteria are not randomized and are 
instead treated per hospital standard practice, followed for safety for 30 days, and then withdrawn.  
Subjects who are enrolled and randomized will be followed clinically for 24 months to assess the 
primary endpoints of patency and freedom from serious adverse events with further follow-up 
extending out to 5 years. 
The primary analysis is an ITT analysis using proportion-based testing.  For the study to be 
considered successful, superiority of Moxy Drug Coated Balloon must be demonstrated for the 
primary efficacy endpoint, and non-inferiority of the Moxy Drug Coated Balloon must be 
demonstrated for the primary safety endpoint.  US and non-US enrollment will be 
contemporaneously monitored throughout the study to ensure approximately 50% of randomized 
subjects occur at US sites.  
15.2  ASSESSMENT OF COMPARABILITY OF TREATMENT GROUPS AND 
POOLABILITY OF SITES AND SECONDARY ANALYSES 
To demonstrate the comparability of the Control to Test subjects, the samples will be compared 
using t-tests or Wilcoxon nonparametric tests for means and X2-tests for proportions: age, gender, 
smoking, obesity, hypercholesterolemia, diabetes mellitus, total target lesion length and maximum 
percent stenosis of the target lesion (via core lab analysis), previous target lesion intervention, ABI 
of the target limb, and Rutherford grade.   
All primary endpoints will also be presented by site, and the sites will be tested for differences in 
the endpoints.  Sites with 3 or fewer randomized subjects will be combined for this purpose.     
An analysis will be performed to examine the potential for interaction of site and treatment group.   
A mixed effects logistic regression model will be fit that includes a fixed effect for treatment 
group, and random effects for site and the interaction of treatment group and site.  If the p-value 
for the interaction term variance component is <0.15, it will be considered evidence of a 
statistically significant interaction effect, and additional analyses will be performed to explore the 
differences between sites to assess their potential causes and whether or not they are clinically 
meaningful.     
All primary endpoints will also be presented by geography (US versus OUS).  An analysis will be 
performed to examine the potential for interaction of geography and treatment group.  A logistic 
regression model will be fit that includes fixed effects for treatment group, geography, and the 
interaction of treatment group and geography.  If the p-value for the interaction term is <0.15, it 
will be considered evidence of a statistically significant interaction effect, and additional analyses 
will be performed to explore the differences between geographies to assess their potential causes 
and whether or not they are clinically meaningful. 

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In addition, a descriptive analysis that examines the impact of important covariates on study results 
will be performed. Baseline covariates are age, gender, smoking, obesity, hypercholesterolemia, 
diabetes mellitus, total target lesion length, and maximum percent stenosis of the target lesion (via 
core lab analysis), previous target lesion intervention, ABI of the target limb, and Rutherford 
grade.  These covariates will be included along with treatment group in a logistic regression model 
in order to understand their potential impact on study results and to account for chance imbalances 
between the randomized groups in these covariates. 
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.  The AT 
dataset will include only those subjects treated with either an investigational or control device, and 
the comparison will be based on the actual device used, not randomized assignment.  The PP 
dataset will include all subjects in the full analysis dataset 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.  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. 
A descriptive analysis will also be reported for the subset of subjects with treated lesions ≥4 cm, 
comparable to the inclusion criteria of ongoing VIVA OPC16  stent registry studies (e.g., SUPERB 
NCT00933270, OSPREY NCT01118117, and DURABILITY II NCT00530712).   
 
15.3   HANDLING OF MISSING DATA 
Endpoints may be missing because subjects have died, have uninterpretable imaging data or have 
withdrawn from the study prior to the time the endpoint is measured.  The primary safety and 
effectiveness endpoints will be analyzed using survival analysis techniques.  In survival analyses, 
unobserved endpoints are a standard part of the analysis; they are known as “censored 
observations”.  As long as the censoring is unrelated to the treatment, this method of handling 
missing endpoints produces unbiased estimates of the freedom-from-event rates. 
The reason for the censoring of all subjects with missing endpoints will be reported; if there is any 
indication that the censoring is related to the Moxy Drug Coated Balloon or to the standard PTA 
catheter, a worst-case analysis will be performed for each primary endpoint, in addition to the 
standard analysis.  In a worst-case analysis, an event will be assumed to have occurred at the time 
the subject discontinued participation in the study for all such subjects in the Test group.  In the 
Control group, all subjects with missing data will be assumed not to have had an event.  In 
 
16Rocha-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. 

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addition, a tipping-point analysis will also be performed, in which assumptions about missing data 
are varied from worst-case to best-case to examine at what point the missing data would alter the 
results of the analysis.  These analyses will constitute sensitivity analyses of the effect of missing 
data on the study results. 
15.4   PRIMARY ENDPOINTS 
Primary Safety Endpoint 
The primary safety endpoint is a composite of freedom from all-cause perioperative (≤30 day) 
death and freedom at 1 year from the following: index limb amputation (above and below the 
ankle) index limb re-intervention, and index-limb-related death.  These events are called “safety 
events” in the following text. 
Primary Efficacy Endpoint 
The primary efficacy endpoint is Primary Patency of the target lesion at 1 year. Primary Patency is 
defined as the absence of target lesion restenosis (defined by DUS PSVR ≥2.5) and freedom from 
target lesion revascularization (TLR).  These events are called “efficacy events” in the following 
text. 
The clinical status of the subject (for assessment of clinical and primary safety endpoints) is established 
prior to performing the required DUS (for assessment of the primary efficacy endpoint). A patent target 
lesion (by core lab DUS analysis) at the 12 month visit without a prior TLR is considered an Efficacy 
Success. 
 
 
15.4.1   PRIMARY SAFETY ENDPOINT: BACKGROUND CONSIDERATIONS & OUTCOME 
EXPECTATIONS 
The Primary Safety Endpoint includes assessment of clinically significant systemic and 
downstream vascular complications at 1 year by assessing freedom from all-cause index limb re-
intervention (e.g. PTA or surgical bypass) for any reason (e.g. embolism, thrombosis, or 
restenosis), all index limb amputations (including both major and minor amputations below-the 
ankle), index-limb-related death, and all-cause perioperative (≤30 day) death. 
Primary Endpoint expectations are estimated from an analysis of data from three randomized trials:   
• The THUNDER trial12, a prospective randomized European clinical trials of another 
manufacturer’s drug-coated balloon (DCB) to a standard uncoated balloon to treat 
femoropopliteal stenosis 
• The FemPac trial13, a prospective randomized European clinical trial of another 
manufacturer’s DCB to a standard uncoated balloon to treat femoropopliteal stenosis 
• The LEVANT I study of the Moxy Drug Coated Balloon, which uses the same API as 
the THUNDER and FemPac DCB, but a different excipient (drug carrier).  Like the 
other studies, the control in the LEVANT I study was a standard PTA balloon. 

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Although the primary composite safety endpoint as defined in the present study is not specifically 
reported in THUNDER and FemPac, the rate is estimated as the rate of freedom from all clinical 
events including death, amputation, any TLR (clinically-indicated or not), embolism or thrombosis 
in THUNDER at 12 months and in FemPac at clinical follow-up between 18 and 24 months (since 
12 month data was not reported).  Clinical outcomes reported for these Control studies and 
LEVANT I are summarized in Table 11: Historic Data for Primary Safety Endpoint Estimation 
below.  
TABLE 11: HISTORIC DATA FOR PRIMARY SAFETY ENDPOINT ESTIMATION 
Study 
Arm 
N 
Events (N) 
Percent 
of 
Subject
s 
Tim
e 
(m) 
Appro
x FF @ 
Time 
Hazar
d 
Rate+ 
Predicte
d FF @ 
12m++ 
TL
R 
Am
p 
T
E 
Deat
h 
Tota
l 
Thunder12 
DCB 
4
8 
5 
2 
2 
2 
11 
22.9% 
12 
77.1% 
0.022 
77.1% 
Contro
l 
5
4 
26 
0 
3 
1 
30 
55.6% 
12 
44.4% 
0.068 
44.4% 
FemPac13 
DCB 
4
5 
6 
0 
1 
6 
13 
28.9% 
18 
71.1% 
0.019 
79.7% 
Contro
l 
4
2 
21 
1 
0 
3 
25 
59.5% 
18 
40.5% 
0.050 
47.9% 
LEVANT 
I 
DCB 
4
9 
6 
1 
0 
1 
8 
16.3% 
6 
83.7% 
0.030 
70.1% 
Contro
l 
5
2 
10 
1 
2 
3 
16 
30.8% 
6 
69.2% 
0.061 
47.9% 
 
+ The hazard rate equals -LN(FF @ time)/time. 
 
++ The predicted FF-event rate at 12 months equals EXP(-hazard*time). 
This analysis is complicated by the fact that there is likely to have been some overlap between the 
adverse events reported in the THUNDER and FemPac studies;  however Lutonix does not have 
access to the raw data, and therefore are  not able to assess to what extent this affects the hazard 
rates.  In addition, subjects that based on unacceptable angiographic results after predilatation are 
likely to require stenting are excluded from the present study, so there may be some inherent 
positive selection bias that was absent in THUNDER and FemPac.  Nevertheless, these factors that 
might increase the primary endpoint rate are at least partially counterbalanced by the fact that the 
above studies did not report many adverse index limb events (such as minor below-the-ankle 
amputations and non-target lesion vascular interventions) that count as safety endpoint failures in 
the present study.  
The most conservative estimates come from the LEVANT I study; the hazard rates in the Test and 
Control groups are more similar in LEVANT I than in THUNDER or FemPac.  The safety 
endpoint success rate of the Moxy Drug Coated Balloon is therefore assumed to be 70% at 12 
months, and of the standard PTA catheter to be 48% at 12 months. 

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15.4.2 PRIMARY SAFETY ENDPOINT:  HYPOTHESES AND SAMPLE SIZE CALCULATION 
Objective:  To assess whether the proportion of subjects with at least one safety event* in the Test 
group is inferior or not inferior to that of Control group through 12-months post-index procedure. 
H0: The proportion of subjects with safety events in the Test group through 12-months 
post-index procedure is clinically inferior to that of the Control group.  
H1: The proportion of subjects with safety events in the Test group through 12-months 
post-index procedure is clinically non-inferior to that of the Control group. 
H0:PTEST  – PCONTROL  ≥       vs.    H1:PTEST  – PCONTROL < ** 
*All-cause perioperative (≤30 day) death, index limb amputation (above and below the ankle), 
index limb re-intervention, and index-limb-related death are ‘safety events’. **δ is the range of 
differences that is considered not clinically important (it also known as the “range of indifference” 
or the “margin of noninferiority”). 
The statistical analysis will be a Farrington & Manning test for non-inferiority of proportions; the 
test will be a one-sided test at α=0.025.  The response variable in each subject will be the presence 
or absence of at least one safety event from the time following the index procedure through 12 
months.  The primary analysis will be ITT.  In addition to the primary ITT analysis, secondary as-
treated analyses and per-protocol analyses will also be reported but may not be the basis of 
labeling claims. 
The proportions at 12-months post-index procedure, and the confidence intervals of these rates in 
each group, will also be reported. 
Sample Size Estimate:  We estimated the sample size under the following conditions: 
• The true 12-month proportion in the Test group is 100% - 70% = 30%.  The true 12-month 
proportion in the Control group is 100% - 48% = 52%. 
• A 2:1 randomization ratio. 
• Farrington & Manning test for non-inferiority of proportions. 
• The Type 1 error,  = 0.025 (one-sided). 
• The Type 2 error,  = 0.10 (Power = 1 -  = 90%). 
• The non-inferiority margin, δ= .05. 
• Subjects who are censored without having an event will be omitted from the analysis. 
 
According to PASS 2008 (using the Farrington and Manning test for non-inferiority of 
proportions), the evaluable sample size required for 90% power is 150 (50 Control plus 100 Test).  
This endpoint is not the sample-size driver of the study.  Randomization of 476 subjects is 
expected to provide at least 405 evaluable subjects, after adjustment for up to 15% censoring) and 
approximately 99% power. 

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15.4.3 PRIMARY EFFICACY ENDPOINT: BACKGROUND CONSIDERATIONS & OUTCOME 
EXPECTATIONS 
The Primary Efficacy Endpoint is Primary Patency of the target lesion at 1 year. Primary Patency 
is defined as the absence of binary restenosis based on DUS peak systolic velocity ratio (PSVR) 
≥2.5 and freedom from TLR.  
In order to facilitate comparison with other ongoing studies and in deference to the threshold used 
in defining the VIVA Physician Group endpoint17, secondary endpoint alternative patency will also 
be reported for PSVR binary restenosis thresholds ≥2.0 and ≥3.0. Compared to threshold PSVR 
≥2.0, the threshold ≥2.5 more accurately reflects clinically significant stenosis and is more 
consistent with angiographic results.18 The primary composite efficacy endpoint as defined in the 
present study is not specifically reported in THUNDER or FemPac, neither of which included 
Doppler ultrasound assessment at 1 year.  
The efficacy endpoint success rate is instead estimated solely from the observed rate of freedom 
from TLR (whether clinically-indicated or not) at 18 to 24 months in these studies.  It is 
noteworthy that only after 2 years do TLR rates exceed 6 month angiographic binary restenosis 
rates. Efficacy events reported for these studies and for the pilot study LEVANT I are summarized 
in Table 12 below.  Efficacy endpoints success rate is estimated in Table 12 from LEVANT I data 
according to both angiographic and DUS criteria for restenosis, even though DUS will be used in 
the LEVANT 2 study. 
 
TABLE 12: HISTORIC DATA FOR PRIMARY EFFICACY ENDPOINT ESTIMATION 
Study 
Arm 
N 
Events 
(N) 
Percent of 
Subjects 
Time 
(m) 
Approx 
FF @ 
Time 
Hazard 
Rate+ 
Predicted FF 
@ 12m++ 
Thunder12 
DCB 
48 
7 
14.6% 
18 
85.4% 
0.009 
89.7% 
Control 
54 
28 
51.9% 
18 
48.1% 
0.041 
61.3% 
FemPac13 
DCB 
45 
6 
13.3% 
18 
86.7% 
0.008 
91.1% 
Control 
42 
21 
50.0% 
18 
50.0% 
0.039 
63.0% 
LEVANT I* 
DCB 
49 
11 
22.4% 
6 
77.6% 
0.044 
59.3% 
Control 
52 
18 
34.6% 
6 
65.4% 
0.072 
42.2% 
LEVANTI** 
DCB 
39 
11 
28.2% 
6 
71.8% 
0.055 
51.6% 
 
Control 
35 
18 
51.4% 
6 
48.6% 
0.120 
23.6% 
* Numbers of events are estimated from the approximate freedom-from-TLR/DUS>2.5 at 6 months. 
** Numbers of events are estimated from the approximate freedom-from-TLR/angiographic patency (<50% stenosis) at 6 months. 
+ The hazard rate equals -LN(FF @ time)/time. 
 
17 Rocha-Singh, K. J. (2007). Performance Goals and Endpoint Assessments for Clinical Trials of Femoropopliteal Bare Nitinol 
Stents in Patients with Symptomatic Peripheral Arterial Disease. Cath and Cardio Inter , 69, 910. 
18 Schlager, O. (2007). Duplex Sonography Versus Angiography for Assessment of Femoropopliteal Arterial Disease in a "Real-
World" Setting. 14, 452-459. 

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++ The predicted FF-event rate at 12 months equals EXP(-hazard*time). 
Note that the hazard rates in the Control and Test groups based on the LEVANT I DUS data are 
more similar than in the THUNDER and FemPac studies or using LEVANT I angiographic data, 
which means that using the LEVANT I DUS data produces the most conservative (i.e. largest) 
study sizes.  So in spite of its limitations, we used LEVANT I DUS data to estimate study sizes for 
the current study. The efficacy endpoint success rate of the Moxy Drug Coated Balloon is 
therefore assumed to be 59% at 12 months, and of the standard PTA catheter to be 42% at 12 
months. 
15.4.4 PRIMARY EFFICACY ENDPOINT: HYPOTHESIS AND SAMPLE SIZE CALCULATION 
Objective:  To assess whether the proportion of subjects with at least one efficacy event* in the 
Test group is equal or not to that of Control group through 12-months post-index procedure. 
H0: The proportion of subjects with efficacy events in the Control group through 12-months 
post-index procedure is equal to that of the Test group. 
H1: The proportion of subjects with efficacy events in the Control group through 12-months 
post-index procedure is not equal to that of the Test group. 
H0: PCONTROL = PTEST       vs.    H1: PCONTROL ≠ PTEST   
*Target lesion restenosis (defined by DUS PSVR ≥2.5) and target lesion revascularization (TLR) 
are ‘efficacy events’. 
The statistical analysis will be a likelihood ratio chi-square test for inequality of binomial 
proportions; the test will be a two-sided test at α=0.05.  The response variable in each subject will 
be the presence or absence of at least one efficacy event from the time following the index 
procedure through 12 months.  The primary analysis will be ITT, and a significant rejection of the 
null hypothesis with results in favor of the Test group will indicate success for this endpoint.  In 
addition to the primary ITT analysis, secondary as-treated analyses and per-protocol analyses will 
also be reported but may not be the basis of labeling claims. 
The proportions at 12-months post-index procedure, and the confidence intervals of these rates in 
each group, will also be reported. 
Sample Size Estimate:  The sample size estimate assumed the following: 
• The true 12-month proportion in the Test group is 100% - 59% = 41%.  The true 12-month 
rate in the Control group is 100% - 42% = 58%. 
• A 2:1 randomization ratio. 
• Likelihood ratio chi-square test for inequality of binomial proportions. 
• The Type 1 error,  = 0.05 (two-sided). 
• The Type 2 error,  = 0.10 (Power = 1 -  = 90%). 
• Subjects who are censored without having an event will be omitted from the analysis. 

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According to PASS 2008, the study evaluable sample size required for 90% power is 
approximately 405 subjects (135 Control plus 270 Test after eliminating the censored subjects, if 
any).   After adjustment for 15% censoring through 12 months, the study size is 476 (317 in the 
Test group and 159 in the Control group) randomized subjects.  This endpoint is the sample-size 
driver of the study.  
15.5    SECONDARY ENDPOINTS 
15.5.1 SECONDARY ENDPOINTS WITH HYPOTHESIS TESTING 
The following secondary endpoints will have hypothesis tests.  No secondary endpoints will be 
tested unless both primary objectives are passed.  All secondary endpoints with hypothesis tests 
will be included in the product labeling.  The primary analysis will be ITT.  In addition to the 
primary ITT analysis, secondary as-treated analyses and per-protocol analyses will also be reported 
but may not be the basis of labeling claims. 
The testing of the secondary objectives will be performed in a hierarchical fashion in the order in 
which they are listed below.  This means that as soon as a null hypothesis is not rejected, no 
further hypotheses will be tested.  This hierarchical testing scheme ensures that the study-wide 
Type 1 error rate is 0.05 when all of the secondary endpoints are tested at α=0.05.   
15.5.1.1 SECONDARY ENDPOINT:  TOTAL TLR AT 12 MONTHS 
Objective:  To assess whether the proportion of subjects with a TLR in the Test group is equal or 
not to that of Control group through 12-months post-index procedure. 
H0: The proportion of subjects with a TLR in the Control group through 12-months post-
index procedure is equal to that of the Test group. 
H1: The proportion of subjects with a TLR in the Control group through 12-months post-
index procedure is not equal to that of the Test group. 
H0: PCONTROL = PTEST       vs.    H1: PCONTROL ≠ PTEST 
The statistical analysis will be a likelihood ratio chi-square test for inequality of binomial  
proportions;  the test will be a two-sided test at α=0.05.  The response variable for each subject will 
be the presence or absence of a TLR by 12 months.     
The proportions at 12-months post-index procedure, and the confidence intervals of these rates in 
each group, will also be reported if the null hypothesis is rejected. 
15.5.1.2 SECONDARY ENDPOINT:  TVR AT 12 MONTHS 
Objective:  To assess whether the proportion of subjects with a TVR in the Test group is equal or 
not to that of Control group through 12-months post-index procedure. 
 

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H0: The proportion of subjects with a TVR in the Control group through 12-months post-
index procedure is equal to that of the Test group. 
H1: The proportion of subjects with a TVR in the Control group through 12-months post-
index procedure is not equal to that of the Test group. 
H0: PCONTROL = PTEST       vs.    H1: PCONTROL ≠ PTEST 
The statistical analysis will be a likelihood ratio chi-square test for inequality of binomial 
proportions; the test will be a two-sided test at α=0.05.  The response variable for each subject will 
be the presence or absence of a TVR by 12 months.     
The proportions at 12-months post-index procedure, and the confidence intervals of these rates in 
each group, will also be reported if the null hypothesis is rejected. 
15.5.1.3 SECONDARY ENDPOINT:  COMPOSITE EVENTS AT 12 MONTHS 
Objective:  The composite event is:  all-cause death at 30 days, and amputation, index-limb 
reintervention, and index-limb-related death at 12 months.  The objective is to assess whether the 
proportion of subjects with an event in the Test group is equal or not to that of Control group. 
H0: The proportion of subjects with an event in the Control group through 12-months post-
index procedure is equal to that of the Test group. 
H1: The proportion of subjects with an event in the Control group through 12-months post-
index procedure is not equal to that of the Test group. 
H0: PCONTROL = PTEST       vs.    H1: PCONTROL ≠ PTEST   
The statistical analysis will be a likelihood ratio chi-square test for inequality of binomial 
proportions;  the test will be a two-sided test at α=0.05.  The response variable for each subject will 
be the presence or absence of an event by 12 months.     
The proportions at 12-months post-index procedure, and the confidence intervals of these rates in 
each group, will also be reported if the null hypothesis is rejected. 
15.5.1.4 SECONDARY ENDPOINT:  COMPOSITE EVENTS AT 24 MONTHS 
Objective:  The composite event is:  all-cause death at 30 days, and amputation, index-limb 
reintervention, and index-limb-related death at 24 months.  The objective is to assess whether the 
proportion of subjects with an event in the Test group is non-inferior to that of Control group. 
H0: The proportion of subjects with an event in the Test group through 24-months post-
index procedure is clinically inferior that of the Control group. 
H1: The proportion of subjects with an event in the Test group through 24-months post-
index procedure is clinically non-inferior to that of the Control group. 
H0:PTEST  – PCONTROL ≥       vs.    H1:PTEST  – PCONTROL < * 

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*where δ = .05 and is the range of differences that is considered not clinically important (it also 
known as the “range of indifference” or the “margin of noninferiority”). 
The statistical analysis will be the Farrington and Manning test for non-inferiority of proportions;  
the test will be a one-sided test at α=0.025.  The response variable in each subject will be the 
presence or absence of at least one event from the time following the index procedure through 12 
months.     
The proportions at 24-months post-index procedure, and the confidence intervals of these rates in 
each group, will also be reported if the null hypothesis is rejected. 
15.5.1.5 SECONDARY ENDPOINT:  PRIMARY PATENCY AT 24 MONTHS 
Objective:  To assess whether the proportion of subjects with an efficacy event in the Test group is 
equal or not to that of Control group through 24-months post-index procedure.  For the definition 
of an efficacy event, please refer to Section 15.4. 
H0: The proportion of subjects with an event in the Control group through 24-months post-
index procedure is equal to that of the Test group. 
H1: The proportion of subjects with an event in the Control group through 24-months post-
index procedure is not equal to that of the Test group. 
H0: PCONTROL = PTEST       vs.    H1: PCONTROL ≠ PTEST   
The statistical analysis will be a likelihood ratio chi-square test for inequality of binomial 
proportions;  the test will be a two-sided test at α=0.05.  The response variable for each subject will 
be the presence or absence of an efficacy event by 24 months.     
The proportions at 24-months post-index procedure, and the confidence intervals of these rates in 
each group, will also be reported if the null hypothesis is rejected. 
15.5.1.6 SECONDARY ENDPOINT:  TOTAL TLR AT 24 MONTHS 
Objective:  To assess whether the proportion of subjects with a TLR in the Test group is equal or 
not to that of Control group through 24-months post-index procedure. 
H0: The proportion of subjects with a TLR in the Control group through 24-months post-
index procedure is equal to that of the Test group. 
H1: The proportion of subjects with a TLR in the Control group through 24-months post-
index procedure is not equal to that of the Test group. 
H0: PCONTROL = PTEST  vs.    H1: PCONTROL ≠ PTEST   
The statistical analysis will be a likelihood ratio chi-square test for inequality of binomial 
proportions; the test will be a two-sided test at α=0.05.  The response variable for each subject will 
be the presence or absence of a TLR by 24 months.     

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The proportions at 24-months post-index procedure, and the confidence intervals of these rates in 
each group, will also be reported if the null hypothesis is rejected. 
15.5.1.7 SECONDARY ENDPOINT:  TVR AT 24 MONTHS 
Objective:  To assess whether the proportion of subjects with a TVR in the Test group is equal or 
not to that of Control group through 24-months post-index procedure. 
H0: The proportion of subjects with a TVR in the Control group through 24-months post-
index procedure is equal to that of the Test group. 
H1: The proportion of subjects with a TVR in the Control group through 24-months post-
index procedure is not equal to that of the Test group. 
H0: PCONTROL = PTEST       vs.    H1: PCONTROL ≠ PTEST   
The statistical analysis will be a likelihood ratio chi-square test for inequality of binomial 
proportions; the test will be a two-sided test at α=0.05.  The response variable for each subject will 
be the presence or absence of a TVR by 24 months.     
The proportions at 24-months post-index procedure, and the confidence intervals of these rates in 
each group, will also be reported if the null hypothesis is rejected. 
15.5.1.8 SECONDARY ENDPOINT:  COMPOSITE EVENTS AT 24 MONTHS 
Objective:  The composite event is:  all-cause death at 30 days, and amputation, index-limb 
reintervention, and index-limb-related death at 24 months.  The objective is to assess whether the 
proportion of subjects with an event in the Test group is equal or not to that of Control group. 
H0: The proportion of subjects with an event in the Control group through 24-months post-
index procedure is equal to that of the Test group. 
H1: The proportion of subjects with an event in the Control group through 24-months post-
index procedure is not equal to that of the Test group. 
H0: PCONTROL = PTEST       vs.    H1: PCONTROL ≠ PTEST  
The statistical analysis will be a likelihood ratio chi-square test for inequality of binomial 
proportions; the test will be a two-sided test at α=0.05.  The response variable for each subject will 
be the presence or absence of an event by 24 months.     
The proportions at 24-months post-index procedure, and the confidence intervals of these rates in 
each group, will also be reported if the null hypothesis is rejected. 
15.5.1.9 SECONDARY ENDPOINT:  TARGET-LIMB-RELATED HOSPITAL DAYS AT 24 MONTHS  
Objective:  To assess whether the number of hospital days associated with the treatment of 
peripheral arterial disease (PAD) in the target limb in the in the Test group is equal or not to that of 
the Control group through 24-months post-index procedure. 

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A hospital day is defined as any day the subject spends as a hospital in-subject or any day that the 
hospital is visited for an emergency-department evaluation or an out-subject procedure.  Only 
those hospital days after the index procedure that are associated with treatment of PAD in the 
target limb will be included in the analysis. The statistical test will be a based on a Poisson 
regression analysis in which the regressor is an indicator for the treatment group and there is an 
offset term for the total days of follow-up for the first 24 months following the index procedure. 
The test will be a two-sided test of the regression coefficient at α=0.05.  The response variable will 
be the number of hospital days each subject experiences in the 24 months following the index 
procedure. 
H0: βtreatment = 0 
H1: βtreatment ≠0 
In the event that the assumptions of the Poisson regression model are not met, a negative binomial 
model will be employed. 
The distribution of hospital days at 24-months post-index procedure in each group, will also be 
reported. 
15.5.2 SECONDARY ENDPOINTS WITH DESCRIPTIVE STATISTICS 
The following secondary endpoints will have descriptive statistics estimated.  For each endpoint, 
the estimated mean and standard deviation or proportion and sample size will be calculated and 
reported for the Control group and for the Test group.  (NOTE:  Some of these endpoints are also 
tested endpoints; these were presented above).  In addition to the primary ITT analysis, descriptive 
statistics will also be estimated for the primary endpoints and for each of the following secondary 
endpoints based on as-treated (AT) and per-protocol (PP) analyses.  In addition, descriptive 
statistics will also be estimated for the subsets of subjects with and without bailout stenting and for 
patients in the PP dataset with and without bailout stenting. 
• Primary safety endpoint in each group as estimated by Kaplan-Meier analysis. 
• Primary efficacy endpoint in each group as estimated by Kaplan-Meier analysis. 
• Primary and secondary patency at 6, 12 and 24 months: 
o By DUS PSVR <2.0 
o By DUS PSVR <2.5 
o By DUS PSVR <3.0 
• 
TLR at 6 and 24 months: 
o Clinically driven 
o Total (clinical and DUS/angiography-driven) 
• 
DUS Clinical Patency (DUS PSVR <2.5 without prior Clinically Driven TLR) 
• 
Change from baseline at 6, 12 and 24 months: 
o Index-limb Rutherford classification 
o Index-limb resting ABI 

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o Walking Impairment Questionnaire score 
o Six-minute Walk Test distance in subjects with no respiratory, cardiac, or 
orthopedic impairments 
o EQ-5D score 
o SF36 v2 score 
• 
Freedom from death, index-limb amputation above ankle, and TVR at 30 days (VIVA 
safety endpoint) 
• 
Freedom from the following at 1, 6, 12, 24, 36, 48 and 60 months: 
o All-cause perioperative (<30-day) death, and from any of the following:  index-
limb amputation (any level), index-limb re-intervention, and index-limb-related 
death 
o All-cause death 
o Amputation (above-ankle) 
o TVR 
o Reintervention for treatment of thrombosis or embolism of the target vessel or its 
distal vasculature 
o Major vascular complication 
o Hospital admissions for cardiovascular events 
• 
Target limb related hospital days at 1 and 2 years.  
 
 

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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) 
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 

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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. 
Probable 
 
The temporal sequence is relevant or the event abates upon 
device application completion/removal or the Event cannot be 
reasonably explained by the subject’s condition. 
Highly 
Probable 
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. 
Probable 
 
The temporal sequence is relevant or the event abates upon 
procedure completion or the Event cannot be reasonably 
explained by the subject’s condition. 
Highly 
Probable 
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 
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 
 
6 
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.