Comparative User Experiences With BD Nano™ PRO 32G Extra Thin Wall Pen Needle vs the Terumo Nanopass® 34G Pen Needle
Phase: NA
Conditions: Diabetes
Sponsor: Becton, Dickinson and Company

Corporate Clinical Development 
CCD-5115.T01 Protocol Template  
Revision 05 
 
Page 1 of 36 
BD Protocol #: DBC-18PENDL01 
Protocol Title: Comparative User Experiences with BD Nano™ PRO 
32G Extra Thin Wall Pen Needle vs the Terumo 
Nanopass® 34G Pen Needle 
 
Current Version Version 4.0 25Feb2019 
Version History Version 1.0 05Dec2018 (Original) 
Version 2.0 19Dec2018 
Version 3.0 06Feb2019 (Site specific amendment) 
Sponsor Becton, Dickinson, and Company 
BD Medical – Diabetes Care 
1 Becton Drive 
Franklin Lakes, NJ 07417 
Sponsor Medical 
Monitor 
 
Stanislav Glezer, MD,  
Worldwide VP, Medical Affairs 
BD Diabetes Care  
Office #: 201.847.5214 
Mobile #: 609.454.7955 
Sponsor 
Risk Assessment 
 Significant Risk (SR)                 
 Non-significant Risk (NSR)  
                                                     
 Minimal Risk 
 
The product information and data disclosed through this protocol are confidential and may 
not be disclosed without prior written consent of Becton, Dickinson and Company. 
This study will be performed in accordance with all stipulations of the protocol and in 
compliance with all applicable BD Policies and Procedures.  This study will be conducted in 
accordance with the ethical principles that originate from the Declaration of Helsinki and the 
Belmont Report. Study conduct will comply with US FDA Regulations, applicable state and 
local regulations, and the Good Clinical Practice guidelines set forth by the International 
Conference on Harmonization (ICH-E6) and ISO14155.  
 
 

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SPONSOR PROTOCOL APPROVAL 
 
Signature below indicates approval of the protocol as written. 
Individual or 
function 
Name 
Signature 
Date 
Medical Affairs 
Team 
Representative 
Shahista Whooley, 
PharmD  
This document is signed 
electronically in the 
eTMF system 
 
Medical Monitor 
Stanislav Glezer, 
MD 
This document is signed 
electronically in the 
eTMF system 
 
Study Statistician 
Julie Berube, PhD 
This document is signed 
electronically in the 
eTMF system 
 
Study Manager 
Jonathan 
Washington 
This document is signed 
electronically in the 
eTMF system 
 
 

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INVESTIGATOR SIGNATURE PAGE 
 
Principal Investigator 
 
 
 
Investigational Site 
 
 
 
 
I have read this protocol and agree to conduct this study in accordance with all stipulations of 
the protocol and in compliance with all applicable Good Clinical Practices and regulations. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Signature of Principal Investigator 
 
 
 
Date 
 
 
 

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Contents 
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ........................................... 7 
1.0 INTRODUCTION ...................................................................................................... 8 
2.0 OBJECTIVES ........................................................................................................... 8 
 Primary Objective ......................................................................................................... 8 
 Secondary Objectives ................................................................................................... 9 
 Exploratory Objectives .................................................................................................. 9 
3.0 STUDY DESIGN ...................................................................................................... 9 
 Overall Study Design .................................................................................................... 9 
 Specification of Study Endpoints ................................................................................ 10 
3.2.1 Primary Endpoints ....................................................................................... 10 
3.2.2 Secondary Endpoints................................................................................... 10 
3.2.3 Exploratory Endpoints ................................................................................. 10 
3.2.4 Safety Endpoints .......................................................................................... 11 
 Acceptance Criteria .................................................................................................... 11 
 Treatment Allocation and Methods to Reduce Bias ................................................... 12 
3.4.1 Randomization ............................................................................................. 12 
3.4.2 Masking/Blinding .......................................................................................... 12 
3.4.3 Skill and Behavior of Persons Interacting with the Device ......................... 12 
 Stopping Rules............................................................................................................ 12 
4.0 STUDY POPULATION ........................................................................................... 12 
 Inclusion Criteria ......................................................................................................... 13 
 Exclusion Criteria ........................................................................................................ 13 
5.0 DESCRIPTION OF STUDY PRODUCTS ............................................................... 14 
 Test Product ................................................................................................................ 14 
 Reference Product ...................................................................................................... 14 
 Ancillary Products ....................................................................................................... 14 
 Product Labeling ......................................................................................................... 15 
 Maintenance and Storage of Study Products ............................................................ 16 
6.0 STUDY METHODS ................................................................................................ 16 
 Screening and Enrollment .......................................................................................... 16 
6.1.1 Demographics/Diabetes History .............................................................. 16 
6.1.2 Visual Inspection of Injection Site ........................................................... 16 
6.1.3 Proficiency .................................................................................................. 17 
6.1.4 Randomization ........................................................................................... 17 
 Study Procedures ....................................................................................................... 17 
6.2.1 Injections ...................................................................................................... 17 
Immediately after each injection the following evaluation will be performed: ...... 18 
After each pair of injections .................................................................................. 18 
After all injections completed ................................................................................ 18 
 End of Visit and Study Completion ............................................................................. 19 
7.0 INTERRUPTION OR DISCONTINUATION OF PARTICIPATION/TESTING .......... 19 

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 Discontinuation of Study Subjects .............................................................................. 19 
 Discontinuation Visits and Follow-up Procedures ...................................................... 19 
 Replacement of Discontinued Subjects/Specimens .................................................. 19 
 Retention of Data from Discontinued Subjects/Specimens ....................................... 19 
8.0 RISK / BENEFIT ASSESSMENT ............................................................................ 20 
 Potential Risks ............................................................................................................ 20 
 Potential Benefits ........................................................................................................ 20 
9.0 SAFETY ................................................................................................................. 20 
 Adverse Event Definitions .......................................................................................... 20 
 Adverse Event (AE) Management .............................................................................. 21 
 Assessment of Adverse Events (AEs) ....................................................................... 21 
 Additional Procedures for Assessing & Reporting Serious Adverse Events (SAE) .. 22 
9.4.1 Reporting Obligations to IRB/EC and Health Authorities ............................ 22 
10.0 INCIDENTS .......................................................................................................... 23 
11.0 RETURN OR DESTRUCTION OF STUDY PRODUCT ........................................ 24 
 Defective or Failed Study Products .......................................................................... 24 
12.0 DATA COLLECTION AND MANAGEMENT ......................................................... 24 
 Source Documents ................................................................................................... 24 
 Case Report Forms (CRF) ....................................................................................... 25 
12.2.1 CRF as Source Document......................................................................... 25 
12.2.2 CRF/Data Transmittal ................................................................................ 25 
 Data Management and Storage ............................................................................... 25 
13.0 STATISTICAL METHODS .................................................................................... 26 
 Sample Size Determination ...................................................................................... 26 
 Data Evaluability ....................................................................................................... 26 
 Statistical Methods .................................................................................................... 26 
 Demographics/Other descriptive information ........................................................... 27 
 Safety Analysis ......................................................................................................... 27 
 Interim analysis ......................................................................................................... 27 
 Additional analyses ................................................................................................... 28 
14.0 QUALITY CONTROL AND ASSURANCE ............................................................ 28 
 Accountability of Study Products .............................................................................. 28 
 Monitoring ................................................................................................................. 28 
 Audits and Inspections ............................................................................................. 28 
 Protocol Deviations ................................................................................................... 29 
15.0 ETHICAL AND REGULATORY STANDARDS ..................................................... 29 
 IRB/EC ...................................................................................................................... 29 
 Informed Consent ..................................................................................................... 29 
 Confidentiality of Data............................................................................................... 29 
 Protocol Modifications............................................................................................... 30 
 Study Discontinuation ............................................................................................... 30 
 Clinical Study Registration ........................................................................................ 30 

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 Publication of Results ............................................................................................... 31 
 Record Retention ...................................................................................................... 31 
16.0 BIBLIOGRAPHY/REFERENCES ......................................................................... 31 
17.0 PROTOCOL REVISION HISTORY ...................................................................... 32 
18.0 APPENDICES ...................................................................................................... 34 
18.1: Gravimetric Leakage Quantification Procedure ...................................................... 34 
 Needle Bending Evaluation ...................................................................................... 35 
18.3 Pen Cleaning Procedure .......................................................................................... 36 
 
 
 

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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
AE 
Adverse Event 
AUC 
Area Under Curve 
BD 
Becton, Dickinson and Company 
BG 
Blood Glucose 
BMI 
Body Mass Index 
cat 
Catalog 
CFR 
Code of Federal Regulations 
CI 
Confidence Interval 
CRF 
Case Report/Record Form 
cm 
Centimeter 
DFSP 
Defective or Failed Study Product 
EDC 
Electronic Data Capture 
FDA 
Food and Drug Administration 
FDAAA 
FDA Amendments Act of 2007 
GCP 
Good Clinical Practice 
G 
Gauge 
HIPAA  
Health Insurance Portability and Accountability Act 
HCP 
Healthcare Practitioner 
ICH 
International Conference on Harmonization 
ICMJE 
International Committee of Medical Journal Editors 
INJ 
Injection 
IRB/EC 
Institutional or Independent Review Board/Ethics Committee 
lpf 
Injection Peak Forces 
mm 
Millimeter 
NDC 
National Drug Code 
NI 
Non-inferiority 
PHI 
Protected Health Information 
PI 
Principal Investigator 
PN 
Pen Needle 
SAE 
Serious Adverse Event 
SD 
Standard Deviation 
SOP 
Standard Operating Procedure 
UADE 
Unanticipated Adverse Device Effect 
VAS 
Visual Analog Scale 
XTW 
Extra Thin Wall 
 
 

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1.0 INTRODUCTION 
Pen needles are a component of pen-based injection systems routinely utilized for parenteral 
administration of medications such as insulin.  In 2010, BD introduced a 4mm x 32G pen 
needle.  At that time, it was the shortest and thinnest pen needle available.  In addition to 
lowering the risk for intramuscular injections, this pen needle was demonstrated to be preferred 
by patients vs. their current pen needles. Since its introduction, competitors have launched 
similar length pen needles with thinner gauge needles, such as 33G and 34G. 
Previous studies reported ethnic differences in pain perception (primary study outcome).1 More 
specifically, Asian subjects compared to other ethnicities demonstrated lower pain thresholds 
and greater pain sensitivity.2, 3, 4, 5 The continuous development of thinner needles is focused on 
the improvement of the injection comfort through the reduction in pain sensation.  It is not clear 
if the difference in needle gauge beyond 32G, is associated with clinically meaningful changes 
in pain sensation. BD is conducting several studies in different ethnic and geographic populations 
to address this question.  Data from this study is intended to support appropriate clinical decision 
making in choosing insulin pen needles in the USA, Japan and other countries. 
The comparative pen needle – Terumo Nanopass – although not commercially available in the 
US, presents the most relevant opportunity for comparison of needles of different gauge. The 
availability of such device in Japan, makes the choice of Japanese American patients logical 
from the perspective of eventual results generalizability, not only in the USA, but also in Japan 
and other countries. Differences in user experience and clinical outcomes may not be limited to 
pain sensation, but also by the hypothesis that thinner gauge Terumo needle will require more 
force to deliver the same dose compared to the wider BD needle.  If a patient does not change 
force, dose delivery with the thinner needle will require more time.  Besides a potential negative 
user experience (more force) this may lead to more insulin leakage from both needle tip and 
insertion site (more time) resulting in incomplete insulin dose delivery.  This may directly impact 
glycemic control. 
The intent of this comparative use study is to determine whether Japanese American patients’ 
experiences are different when using the BD Nano™ PRO 4mm x 32G extra thin wall, 5-bevel 
pen needle (herein referred to as BD Nano™ PRO) vs the Terumo Nanopass® 4mm x 34G 
(thinner gauge) pen needle (herein referred to as Terumo Nanopass®).  These experiences 
include the perceived force to deliver dose, the ability to deliver the full dose (measured by 
leakage), injection pain and bending. 
 
 
2.0 OBJECTIVES 
 Primary Objective 
Demonstrate non-inferiority of the BD Nano™ PRO pen needle compared to the Terumo 
Nanopass® pen needle for injection pain. 
 

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 Secondary Objectives 
Demonstrate superiority of BD Nano™ PRO vs Terumo Nanopass® pen needle for the 
following: 
 
Leakage from the needle tip and the injection site (measurements combined) after 
removal from body  
 
Subject perceived force required to deliver dose  
 
Patient end needle bending after removal from body  
 
If primary outcome demonstrates non-inferiority, then evaluate for superiority of 
Nano™ PRO vs Terumo Nanopass®  
 
 Exploratory Objectives 
Compare BD Nano™ PRO vs Terumo Nanopass® for the following: 
 
Injection time 
 
Patient end needle breaking at any time 
 
Survey responses pertaining to subjective assessments of pen needle characteristics 
3.0 STUDY DESIGN 
 Overall Study Design 
This is a subject partially blinded, block randomized, prospective, single-visit, multi-center 
study to compare user experiences with BD Nano™ PRO pen needle vs. the thinner 
commercially available Terumo Nanopass® pen needle. The study will include a minimum of 
55 Japanese American study subjects having Type 1 or Type 2 diabetes. 
Study conduct will consist of one 60 to 120 minute Site visit in which pre-set doses of saline 
will be abdominally delivered by Subjects via a reusable insulin pen device. All pen needles 
will be attached by Study Staff and pen needle outer cover and inner shield will be removed 
for subjects. Subjects are to perform 12 injections into the abdomen (6 pairs of injections). 
Pairs of injections will be evaluated and each pair will contain one BD Nano™ PRO and one 
Terumo Nanopass® pen needle. 
Subjects will not see pen needle labels or be informed which pen needle is being used to 
inject.  The BD Nano™ PRO has a distinct configuration and subjects will most likely notice 
the difference vs the Terumo Nanopass®.  Subjects will not be informed of the Terumo 
Nanopass® brand, length or gauge. 
The pen needle order within the pairs of injections will be randomized for each subject and 
the pairs will be randomized to various abdominal injection sites within each subject.  
Besides being informed of the requirement to insert the pen needles ‘straight-in’ 
(perpendicular), subjects will be instructed to use their usual injection technique. 

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 Specification of Study Endpoints 
3.2.1 Primary Endpoints 
 
Injection Pain 
o Each Subject will evaluate pain after completion of each pair of injections 
using a 15 cm relative Visual Analog Scale (VAS).   
3.2.2 Secondary Endpoints 
 
After each injection:  
o Leakage  
 
After saline delivery equivalent to 30U of U100 insulin (0.3mL) 
and Subject removal of pen needle from body, Study Staff will 
use the provided materials and scale to absorb leakage from the 
pen needle tip and injection site to measure the amount of 
leakage. 
 
Leakage will be considered to be present if measurement is 
equivalent to or greater than 5% of dose (equivalent to or greater 
than 1.5U of U100 insulin – equivalent to ≥0.015g) 
o Bending – patient-end cannula 
 
Study Staff will use a provided needle bend scale and visually 
inspect pen needles to determine the presence of bending.  If 
present, study staff will determine and document degree of bend 
with the provided scale. For the purpose of answering the study 
objective, needle bend will be considered >2 on the bend rating 
scale. 
 
After each pair of injections: 
o Injection force  
 
Each Subject will evaluate perceived injection force after each 
pair of injections using a 5-point Likert scale (from 1st injection 
required much less force to deliver medication to 2nd injection 
required much less force to deliver medication). 
Which pen needle required less force or effort to deliver the dose? 
1st injection 
significantly  
less force or 
effort 
1st injection 
slightly less 
force or 
effort 
Both 
injections 
about the 
same 
2nd injection 
slightly less 
force or effort 
2nd injection 
significantly  
less force or 
effort 
 
3.2.3 Exploratory Endpoints 
 
During each injection: 
Injection time – includes the following time periods for each injection 

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1) 
Time from when subject 1st pushes injection button to time button fully 
depressed  
2) 
Time from when injection button fully depressed to when pen needle 
removed from body 
3) 
Total injection time – the 2 time periods above combined  
 
After each injection:  
o 
Breaking  
 
Study Staff will record any patient end needle breakage.  
Breakage is defined as the patient-end metal cannula separated 
into two pieces. 
 
After all injections completed: 
o 
Survey responses 
 
Subject completes the following 5-point Likert scale survey 
(from Disagree to Agree).  Subject will be instructed to respond 
to the questions based on their usual (in-home use) injection 
experience.  Subject responses to survey questions will be 
tallied. 
 
Disagree 
 
Somewhat 
Disagree 
 
Neutral 
 
Somewhat 
Agree 
 
Agree 
 
 Injection pain affects my level of satisfaction with my 
treatment. 
 Injection pressure needed to deliver the dose affects my level 
of satisfaction with my treatment. 
 Post injection leakage increases my level of concern that I 
may not be receiving my full dose of medication. 
 A bent needle increases my level of concern about the 
reliability of my injection. 
3.2.4 Safety Endpoints 
 
Occurrence of adverse events will be evaluated, recorded, and followed up as 
required. 
 Acceptance Criteria 
Primary Objective:   
o 
BD Nano™ PRO non-inferior to Terumo Nanopass® for injection pain with 
partially blinded injections based on relative VAS, where -75mm indicates 

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worse pain for BD Nano™ PRO and +75mm indicates worse pain for Terumo 
Nanopass® with a non-inferiority criterion of -10mm.    
 
Secondary Objective:   
o 
The BD Nano™ PRO will be evaluated for superiority vs Terumo Nanopass® 
for leakage, injection force, and bending.  
o 
If the BD Nano™ PRO demonstrates non-inferiority for injection pain for the 
Primary Objective, compare the BD Nano™ PRO vs Terumo Nanopass® for 
superiority.  
 
Exploratory Objectives:  
o 
No formal acceptance criterion has been established for the following 
objectives: time to deliver dose, dwell time, and survey responses after all 
injections completed.  
 
 Treatment Allocation and Methods to Reduce Bias  
3.4.1 Randomization 
The order of the pen needles within the pairs and abdominal injection sites for each pair 
will be randomized across each Subject. Injection site diagram will be provided to assist 
in complying with site randomization. 
3.4.2 Masking/Blinding 
Subjects will be blinded to pen needle randomization, order of pairing, and will not be 
informed of needle type.  Since the BD Nano™ PRO and the Terumo Nanopass® are 
designed differently, subjects will be aware which pen needle type is being used, but not 
the brand or needle gauge. 
3.4.3 Skill and Behavior of Persons Interacting with the Device 
Before study participation, without any verbal or written support, all Subjects must 
demonstrate to the Study Staff proficiency injecting with an insulin pen into an injection 
model.  All subjects will be given up to 10 attempts to demonstrate proficiency.  Based 
on the proficiency checklist, subjects will be required to perform three ‘straight in’ 
(perpendicular) injections in addition to other required tasks in order to take part in the 
study injections. 
 Stopping Rules 
No stopping rules for the study have been developed by the Sponsor.  The Principal Investigator 
is responsible for suspending study enrollment for reasons of Subject/Clinician safety and well-
being.  
4.0 STUDY POPULATION 
This study will enroll a minimum of 55 Japanese American subjects with Type 1 or Type 2 diabetes 
who use an injection pen system to deliver their insulin and/or Victoza. A minimum of 35 subjects 
must self-attest to either being born in Japan or having at least one parent or one grandparent 
born in Japan. 

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 Inclusion Criteria 
Male and female patients will be considered for participation in the study if they fulfill the following 
conditions:  
a. Self-attesting Japanese American adults 18 to 75 years of age (inclusive)  
b. Self-attest to Japanese descent 
c. Diagnosed with Type 1 or Type 2 diabetes 
d. Self-injecting using an injection pen for ≥3 months with any pen needle 
e. Injecting a minimum of ≥10 units of insulin and/or Victoza at least once per day 
f. Able to demonstrate proficiency using an injection pen into an injection model 
f. Able and willing to provide informed consent 
g. Able and willing to complete all study procedures 
 
 Exclusion Criteria 
Subjects with any one of the following characteristics will be excluded from participation in this 
study: 
a. Not self-injecting (for example injections completed by a family member) 
b. Self-injecting with a pen injector for less than 3 months 
c. Unwilling to inject into abdomen 
d. Unwilling to have hair at the injection area reduced with an electric razor if it is 
determined the hair will interfere with leakage evaluation 
e. Failure to confirm which pen needle (gauge and needle length) subject is currently 
using.  To confirm, subject may be asked to bring their pen and pen needles to the 
site or site staff may confirm via medical record or pharmacy.  
f. Pregnant (self-attestation)   
g. Currently taking anti-platelet or anticoagulant therapy (up to 162 mg per day of 
aspirin is permitted).  
h. History of a bleeding disorder 
i. 
History of recurrent dermatological conditions or skin disorder (e.g., psoriasis, 
eczema)  
j. 
Gross skin anomalies and abnormalities located at or very close to the injection sites 
that would significantly limit available injection space.  
k. History of symptomatic low blood pressure or history of fainting (syncope) during 
hypodermic injections   
l. 
Use of any analgesic medications within 24 hours of first study injection, and during 
the study (up to 162 mg per day of aspirin is permitted).  

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m. A current or previous medical or physical condition that, in the opinion of the 
investigator, would place the patient at risk or make them unable to perform study 
procedures or has the potential to confound interpretation of the study results 
n. Currently participating in another pen needle study 
o. Employed by, or currently serving as a contractor or consultant to BD or any diabetes 
injectable medication, injection pen, or pen needle manufacturer 
5.0 DESCRIPTION OF STUDY PRODUCTS 
Pen needles are a component of pen-based injection systems routinely utilized for parenteral 
administration of medications such as insulin. A pen needle consists of a doubled ended cannula that is 
assembled into an injection-molded plastic hub using adhesive. The hub has threads, which allow it to 
be screwed onto the pen-injector device. This allows the Non-Patient (NP) end of the needle to penetrate 
through the rubber septum of the pen cartridge to create the fluid flow path. The pen needle device 
interfaces with the delivery site providing a conduit for delivery into the subcutaneous tissue space. Pen 
needles will be attached and primed per manufacturer’s instructions with 0.9% sterile saline. A new pen 
needle will be utilized for each injection. 
 
 Test Product 
 
BD Nano™ PRO 4mm x 32G XTW 5-bevel pen needle 
 
The BD pen needle to be used in this study has a 32G extra-thin walled 
cannula with a nominal length of 4mm, and a 5-bevel tip  
 Reference Product  
 
Terumo Nanopass® 4mm x 34G  
 
The Terumo Nanopass will be labeled “For Investigational Use Only” as 
this product is not currently available for sale in the US. 
 Ancillary Products 
 
Sanofi ClikSTAR® Insulin Reusable Pen  
Note: Either a new or cleaned ClikSTAR® Insulin Reusable Pen will be used for 
each subject depending on site preference. See Appendix 18.3 for Pen Cleaning 
Procedure). 
 
Pen needles (for pen/pen needle proficiency evaluation) 
 
Pen needle removal fixtures 
 
Electric shaver/razor (if injection area has excessive hair that will interfere with 
leakage evaluation) 
 
Antiseptic pads 
 
Bandages  
 
Analytical Scale and required ancillary scale supplies (e.g. marble slab,  calibrated 
weight) 
 
Injection Pads 
 
Cellulose Spears  
 
Plastic Falcon Tubes 
 
3mL 0.9% Sodium Chloride Injection Cartridges 

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0.9% Sodium Chloride Injection, (Mfd for Becton Dickinson by Baxter Pharmaceutical 
Solutions LLC, Bloomington, IN, USA). 
 
Placebo Injection Solution: 0.9% Sodium Chloride Injection, 3cc Cartridge. The sterile 
0.9% saline cartridges were aseptically manufactured and filled by Baxter 
Pharmaceutical Solutions LLC using cGMP for Becton Dickinson. The cartridges met 
all performance requirements, including toxicology and sterility acceptance criteria, 
outlined in the BD Standardized Cartridge Specification. The sterile 0.9% saline 
cartridges will be inserted into commercially available pen systems to provide the 
necessary placebo reservoir.  
 
Note: New pen cartridges will be utilized for each subject and will not be reused 
between subjects. 
 
 Product Labeling 
Investigational devices (or the immediate packaging) shall be labeled in accordance with 
regulatory requirements, including the following statement: “CAUTION-Investigational device. 
Limited by Federal (or United States) law to investigational use.” The BD Nano™ PRO unit label, 
at minimum on its immediate package, must indicate “For Investigational Use only”, with full 
statement on the outer packaging.  The Terumo Nanopass®, must also indicate “For 
Investigational Use only”, with full statement on the outer packaging. Refer to Study Supply Plan 
for further details on labeling requirements and saline cartridges process/certification.  
For BD Nano™ PRO investigational products, box labeling will also include at a minimum: 
o Product Identification 
o Manufacture name and location 
o EWO/Batch# 
o Use by/expiration date 
o Sterility Claim (sterile or non-sterile) 
o “For Investigational Use only” 
 
Saline Cartridge Label Content 
 

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All other ancillary products will be supplied as labeled by the manufacturer.  
 Maintenance and Storage of Study Products 
All study products will be stored according to the manufacturer’s instructions.  Refer to section 
11.0 of the protocol for additional instructions regarding product disposition during the study and 
upon study completion (e.g., disposal, return or destruction, defective products). 
6.0 STUDY METHODS 
 Screening and Enrollment 
Before study start, investigational Site will ensure the following: 
1. Analytical scales for leakage assessment are set up and calibrated by trained personnel. 
2. All Study Staff assigned to the following specific tasks will be trained and demonstrate 
proficiency with procedure: 
a. Set up pen/pen needle system  
b. Timing injection duration 
c. Leakage measurements 
d. Measure needle bend 
e. Needle removal 
 
If site cannot confirm which pen and pen needle (gauge and length) the subject is currently using, 
the subject must bring their injection delivery system(s) (pen and pen needle) with them to the 
Site. Subjects will also be asked to wear comfortable clothes to the Site on study day to enable 
easy accessibility to injection site area.  
 
Prior to study participation, every potential Subject must provide written informed consent and will 
be assigned a Subject number. After being presented with an overview of the study procedures, 
each Subject will be given ample time to review the consent form and ask any questions about 
the procedures.  If the Subject agrees to participate in the study he or she will sign the Informed 
Consent.  
This study requires one subject visit of approximately 60-120 minutes. Once consent has been 
obtained the following information will be collected and procedures will be performed to determine 
whether the subject meets the eligibility requirements.  
6.1.1 Demographics/Diabetes History 
Subjects will be asked a number of background and demographic questions to ensure 
they meet the study-specific eligibility criteria. The PI or Investigator will review the medical 
history information self-reported by the Subject; this information will be recorded in the 
source documents. Information collected will include, but is not limited to age, gender, 
ethnicity and diabetes history (Type 1 or Type 2 diabetes, current injection therapy, current 
pen needle, typical injection site(s)).   
6.1.2 Visual Inspection of Injection Site 
A visual assessment of the injection site area will be performed to determine if any obvious 
skin anomalies or imperfections that would significantly limit available injection sites, (e.g. 
redness, swelling, moles, marks, bruises, cuts, abrasions, discoloration, tattoos, masses, 

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lipohypertrophy and or any other abnormalities).  Study Staff will determine if the hair at 
the injection sites will need to be removed (with provided electric shaver) prior to injections. 
Note: excessive hair must be removed to allow measurements of leakage. 
6.1.3 Proficiency 
Subjects will be asked to perform up to 10 mock injections into an injection pad with a 
provided saline pen to demonstrate proficiency in performing pen injections. A subject will 
be considered proficient once they have achieved 3 proper injections (e.g. injection 
‘straight in’ (perpendicular)) in addition to other tasks listed in the proficiency checklist. 
With a pen needle pre-attached and primed by Study Staff, the Study Staff will use a 
checklist to determine successful proficiency of the Subject to perform an injection using 
the ClikSTAR Pen. If the Subject is unable to demonstrate proficiency, s/he will be 
discontinued from the study.  
6.1.4 Randomization 
Upon successful completion of proficiency, each Subject will be assigned a randomization 
number. 
 
 Study Procedures 
6.2.1 Injections 
 
Subjects will be informed that “these pen needles are to be inserted ‘straight-in” 
(perpendicular)Subjects will be provided with an Insulin Reusable Pen with saline 
cartridges in place and the pen needles attached, primed, and set to 30U.  (A 
new ClikSTAR® Insulin Reusable Pen will be used for each subject at specific sites; 
subjects at remaining sites may use a new or cleaned ClikSTAR® Insulin Reusable 
Pen).   
 
Each injection pair will include: 
o 1 pen with the BD Nano™ PRO pen needle  
o 1 pen with the Terumo Nanopass® pen needle  
 
Using their usual injection technique, Subjects will inject saline with 
the pair of pens into their abdomen per Study Staff instruction and 
according to the randomization schedule.  
 
If subject inserts at an acute angle or uses a skin pinch up, it is 
allowable under this study protocol but should documented on the 
study source. 
o The location of the injection sites will be randomized  
o Each injection will be at least 1 inch from the previous injection 
 
 
During needle injection, Study Staff will record two times: 
o From initial pressing of injection button (dose set knob), to button fully 
depressed  
o From initial pressing of injection button to the removal of the needle from body  

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Immediately after each injection the following evaluation will be performed:  
 
Study Staff will use the provided materials and scale to absorb leakage from the pen 
needle tip and injection site to measure the amount of leakage (refer to Appendix 18.1 
for leakage measurement procedure). If any bleeding is observed, this will be noted 
and leakage measurement will only be collected from the pen needle tip.   Leakage 
measurement amounts will not be discussed in the presence of the Subject. 
 
Study Staff will visually inspect each needle for the presence of bending and/or 
breakage.  If no bending is visually observed, Site Staff will record a score of “0” and 
the pen/needle will be placed in the pen needle disposal fixture.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If bending is visually observed, the pen/pen needle will be placed on the bend scale 
(refer to Appendix 18.2).  The degree of bending will be assessed and scoring 
recorded by Study Staff.  Post scoring, the pen/needle will be placed in the pen needle 
disposal fixture.  The pen needle disposal fixtures, along with all used pen needles, 
will be returned to the Sponsor.  
 
The Subject will then inject the subsequent pen/pen needles into the site according to 
randomization schedule for a total of six pairs (total of twelve injections) 
After each pair of injections 
 
Subjects will complete a 15 cm relative VAS for injection pain and Likert-scale 
assessment for perceived injection force  
After all injections completed 
 
Additional survey questions to be completed 

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Study staff will follow the same procedures for each pen/pen needle set as noted above. 
 End of Visit and Study Completion  
 
The subjects will be discharged from the Site following completion of the study procedures, 
when their injection sites show no evidence of bleeding, and when they are comfortable 
leaving the Site.  
 
Subjects will be instructed to contact the PI or designee if they experience any new, or 
worsening signs and symptoms at the injection sites after leaving the Site. 
 
All adverse events occurring with Subjects during the study will be recorded and followed 
until resolution as appropriate. 
7.0 INTERRUPTION OR DISCONTINUATION OF PARTICIPATION/TESTING  
 Discontinuation of Study Subjects 
Subjects may request withdrawal from the study at any time or may be withdrawn at the discretion 
of the Principal Investigator for any of the following reasons: 
 
Adverse Event/Concurrent Illness 
 
Noncompliance with study requirements or restrictions 
 
Failure to meet ongoing inclusion criteria, or development of an excluding condition  
 
Protocol deviation 
 
Withdrawal of consent  
 
Subject is lost to follow up  
 
Administrative issues 
 
Any other reason which, in the opinion of the PI, makes the Subject’s participation in the 
study not in his or her best interest. 
 Discontinuation Visits and Follow-up Procedures  
For Subjects discontinued due to adverse events, the clinical course of the event will be followed 
according to accepted standards of medical practice until the event resolves, stabilizes, or in the 
opinion of the Investigator, is no longer considered clinically significant. 
 Replacement of Discontinued Subjects/Specimens 
Recruitment of 60 Subjects is anticipated to accommodate potential subject attrition. 
 
 Retention of Data from Discontinued Subjects/Specimens 
No data will be collected from Subjects/specimens after the point of discontinuation except as 
needed to follow ongoing adverse events.  All study data collected from the Subject up to the 
point of discontinuation will be recorded on the Case Report Form, entered into the study 
database, and included in subsequent analyses, as appropriate. 

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8.0 RISK / BENEFIT ASSESSMENT  
 Potential Risks 
The risks to the Subject are non-significant and the findings may reveal information that may 
improve medical care for persons with diabetes. The potential benefit to medical practice 
outweighs the non-significant differential risk experienced by the study Subject compared with 
current standard of care. As a result of inserting a pen needle, Subjects may experience pain, 
bleeding, or local infection. However, given the size of the investigational pen needles (4mm x 
32G or smaller) and the procedures being used in disinfecting the skin and pen devices prior to 
inserting the pen needle, these risks are negligible. 
Risks associated with a pen needle injection may include: 
• 
Discomfort or pain 
• 
Fainting 
• 
Bleeding 
• 
Bruising 
• 
Redness 
• 
Infection 
 Potential Benefits 
There are no direct benefits to the Subject for participation in this study.  The findings may reveal 
information that will allow for a better understanding of pen needles, and thus may improve 
medical care for persons with diabetes. 
9.0 SAFETY 
 Adverse Event Definitions 
Adverse Event (AE):  Any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom or disease in a Subject that is temporally associated with the use of an 
investigational product or procedures, even if the event is not considered to be related to the study 
product or procedures.  
This includes events not seen at baseline and events that have worsened if present at baseline.  
The term AE will refer to all adverse events (serious and non-serious) occurring during 
participation in a study of either investigational devices and/or drugs.  
Serious Adverse Event (SAE):  An SAE is any AE occurring during study participation that 
results in any of the following outcomes: 
 
Death  
 
Life Threatening (refers to any event in which the Subject was at risk of death at the time 
of the event; it does not refer to an event which hypothetically might have caused death if 
it were more severe) 
 
Hospitalization or prolongation of a hospital stay 
 
Persistent or significant disability or incapacitation (refers to any event which results in a 
substantial and/or permanent disruption of the Subject’s ability to carry out normal life 
functions) 
 
Required intervention to prevent permanent impairment/damage 

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 
Congenital anomaly/birth defect 
 
Important medical event that may require intervention to prevent one of the preceding 
conditions.  
Unanticipated Adverse Device Effect (UADE):  Any serious adverse effect on health or safety 
or any life-threatening problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or degree of incidence in the 
investigational plan or application (including a supplementary plan or application), or any other 
unanticipated serious problem associated with a device that relates to the rights, safety, or welfare 
of Subjects (21CFR-812.3(s)). Refer to Protocol Section 8.1 (Potential Risks) for a list of 
anticipated adverse events, signs or symptoms. 
 Adverse Event (AE) Management 
Subjects will be questioned in an open-ended manner throughout the conduct of the study as 
appropriate for any new or worsening undesirable signs or symptoms they may have experience 
since being exposed to the study product. Elicited signs and symptoms must be comprehensively 
documented on the appropriate source documentation.  
Each sign, symptom, disease or illness reported must be evaluated by the Investigator or 
designee to determine if it meets the definition of an Adverse Event.  
The clinical course of the event will be followed according to accepted standards of medical 
practice until the event resolves, stabilizes, or in the opinion of the Investigator, is no longer 
considered clinically significant.  The Investigator must supply the Sponsor with information 
concerning the follow up and/or resolution of the AE.  
Some reported or observed signs and symptoms are inherent to subcutaneous injection and are 
likely to occur transiently for nearly all Subjects in this study.  Such signs or symptoms will not be 
considered AEs as long as they are mild (transient, easily tolerated, no interference with daily 
activities) and the Principal Investigator agrees. The following will not be not be considered AEs: 
 
Mild, self-limited pain, swelling at the injection site and presence of wheals 
 
Mild bruising at the injection site 
 
Mild self-limited bleeding at the injection site 
 
However, these signs and symptoms must be considered AEs and documented on the Adverse 
Event CRF  should any of them occur in such a way that the extent or nature of the experience 
exceeds that normally associated with the procedure, as judged by the Subject to be excessive 
pain, bruising or bleeding. 
All needle breaking that results in a cannula remaining in the body either partially or fully, must 
be considered an AE and documented on the Adverse Event CRF. 
 
 Assessment of Adverse Events (AEs) 
All AEs must be assessed for Seriousness, Severity, and Relationship. All AEs, regardless of 
classification, must be comprehensively documented in the CRF and on the SAE form, if 
applicable, and reported to BD.  This includes AEs related to marketed study products. The 
following information about the event is to be reported on the AE CRF: 

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 
Seriousness, classified as: Non-Serious or Serious 
 
Severity,  classified as: 
o Mild: Transient symptoms, easily tolerated, no interference with daily activities 
o Moderate: Marked symptoms, moderate interference with daily activities, tolerable 
o Severe: Considerable interference with daily activities, intolerable 
 
Relationship to the study product or study procedures:  
o Not Related: Evidence suggests absolutely no possible causal relationship 
between the event and the investigational study device (or procedures). 
o Unlikely Related: Evidence suggests that other possible causes or contributing 
etiological factors may have caused the event other than the investigational study 
device (or procedures). 
o Possibly Related: Evidence suggests a causal relationship between the event and 
the investigational study device (or procedures) cannot be ruled out 
o Related: Evidence suggests a reasonable causal relationship between the event 
and the device (or procedures) is likely 
In addition, the following should be recorded for each AE: 
 
Action(s) taken to remedy the AE, including change in study treatment or participation, or 
medical/surgical treatments 
 
Duration of the AE from onset through resolution, as applicable 
 
Cause (including suspected product/procedure and/or other cause) 
 
Outcome of the event, including resolution and sequelae, as applicable 
 Additional Procedures for Assessing & Reporting Serious Adverse Events (SAE) 
SAE criteria are specified in Section 9.1.  All SAEs must also be assessed by the Investigator and 
Sponsor Medical Monitor to determine whether an SAE is expected or unexpected. An adverse 
event will be considered unexpected or unanticipated if the nature, severity or frequency of the 
event is not consistent with the risk information previously described in the protocol, Informed 
Consent, or Investigator’s Brochure (if applicable). 
Any adverse event meeting the criteria for ‘Serious’, regardless of the Investigator’s opinion of 
expectedness or relationship to the study product, must be reported to BD within 24 hours. The 
Investigator or designee must report the event by telephone or email to the Study Monitor. In 
addition to reporting the SAE to the Study Monitor, the Investigator must also submit a completed 
SAE form to the BD Trial Safety Dept. via fax or email listed below within 24 hours of receipt of 
the information. 
 
Safety Email:  BD_Trial_Safety@BD.com 
 
Safety Fax Line: (US) 1-201-847-5688 
 
Medical questions about study safety issues and serious adverse events can be directed to 
the Sponsor Medical Monitor. 
9.4.1 Reporting Obligations to IRB/EC and Health Authorities 
The Investigator must report any adverse events which are serious, unanticipated/unexpected 
and probably or possibly related to the study product or procedures to the reviewing IRB/EC.  

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This report must be submitted as soon as possible, but in no event later than 10 working days 
after the Investigator first learns of the event.   
The Investigator may also have additional responsibilities for AE reporting to their governing 
Health Authority which they are responsible for identifying and fulfilling. 
The Sponsor will provide results of any evaluation of an unanticipated/unexpected adverse 
device effect to appropriate Health Authorities, to all Investigators, and to all reviewing 
IRB/ECs within 10 working days after the Sponsor is notified of the event.  If the Investigator 
wishes to assume responsibility for filing reports of evaluation results to their own IRB/EC in 
lieu of the Sponsor, they must notify the Sponsor in writing of this preference and must retain 
evidence of their compliance with this requirement. 
BD will comply with all other Sponsor safety reporting requirements and timelines for other 
entities (e.g., Data Safety Monitoring Boards) and local health authorities in other countries 
where this study or other studies with the same product are being conducted, in compliance 
with study procedures and applicable local regulatory requirements and BD Standard 
Operating Procedures.  
10.0 INCIDENTS 
A Clinical Study Incident is defined as any problem or issue involving the investigational product(s), 
reference methods, associated procedures or equipment, or represents a product-related injury (or 
potential for injury) to study Subjects or personnel as a result of execution of this protocol.   Clinical Study 
Incidents may adversely (or potentially adversely) affect human safety, the integrity of the evaluation 
data, or the operation of devices or systems, and warrant prompt attention.  
Incidents involving injury to study Subjects will also be reported as Adverse Events (refer to Section 9).   
Examples of Clinical Study Incidents that are not Adverse Events might be mislabeling or adulteration 
of the investigational device, equipment or device malfunctions, and errors in the device 
instructions, damage to devices caused by shipping or handling or improper storage, or injury to 
study personnel due to execution of the protocol.  If appropriate, an Incident may also be documented 
and reported as a protocol deviation.  
Study-specific procedures for reporting Incidents, as well as adverse events and protocol deviations, will 
be provided to the study Site prior to study execution.  The Monitor should be contacted immediately 
when the Site becomes aware of or suspects any defective or malfunctioning product. This includes: 
• 
Products that are involved in Study Incidents, 
• 
Products that are found to be expired, damaged or defective, 
• 
Products that are possibly the cause of an adverse effect, regardless of whether the product was 
believed to be damaged, defective or malfunctioning.  
Such products (whether investigational or marketed) should be segregated and returned with appropriate 
documentation to the BD address below, unless instructed otherwise by BD. The Study Monitor should 
be contacted with any questions regarding return of study products. BD will supply mailing kits specifically 
intended for product contaminated with potentially bio-hazardous material. 

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11.0 RETURN OR DESTRUCTION OF STUDY PRODUCT  
Unless instructed otherwise by BD, the Investigator will return all used pen needles (secured in the 
provided system), unused or unopened test, reference, and ancillary study products to BD.  At the 
conclusion of the study, and as appropriate during the course of the study, any products, supplies or BD 
equipment that are required to be returned will be shipped to BD at the address below, unless instructed 
otherwise: 
Falguni Patel 
Becton, Dickinson and Company 
1 Becton Drive, G334L 
Franklin Lakes, NJ 07417 
201-847-4688 
 Defective or Failed Study Products  
DFSP: The term DFSP generally refers to any damaged, malfunctioning, or failed product 
(confirmed or suspected) identified at the investigational Site.  DFSP includes: 
 
Products that are involved in Study Incidents, 
 
Products that are found to be damaged or defective, 
 
Products that fail or malfunction during the study,   
 
Study products rendered unusable due to Subject/patient/Site Staff mis-use or 
improper storage conditions,  
 
Products that are possibly the cause of an adverse effect, regardless of whether the 
product was believed to be damaged, defective or malfunctioning.  
The Monitor must be contacted immediately when the Site becomes aware of any DFSP.  All 
DFSP (whether investigational or marketed) should be segregated and returned with appropriate 
documentation to the BD address above, unless instructed otherwise by BD. The Study Monitor 
should be contacted with any questions regarding return of study products. BD will supply mailing 
kits specifically intended for product contaminated with potentially bio-hazardous material. 
Depending on the intended use of the study products in the study (e.g., if assessing failure 
modes), there may be exceptions or additions to the requirements for DFSP/Incident 
documentation; these will be described in this protocol or the study-specific Monitoring Plan. 
12.0 DATA COLLECTION AND MANAGEMENT  
 Source Documents 
Source data includes all information in original records (and certified copies of original records) of 
clinical findings, observations, or other activities (in a clinical study) used for the reconstruction 
and evaluation of the study. Source data are contained in source documents (original records or 
certified copies) and are used to verify the authenticity of information recorded on the Case Report 
Form (CRF).  Typical source documents include the hospital chart, medical office file, laboratory 
report, clinician notes, patient record, recorded data from automated instruments or other 
documentation prepared and maintained by the investigator/staff or ancillary services which 
contains a record of all observations and other data pertinent to the investigation on a study 
Subject.   

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The investigator is required to maintain original source documents at the Site.  Should an original 
source document (e.g., an instrument printout, direct entry CRF) need to be forwarded to BD for 
data entry, the Site must retain a clearly designated certified copy.  The Study Monitor will confirm 
that procedures for copy certification have been established at the Site prior to transmittal of any 
original source documents.  
 Case Report Forms (CRF) 
The case report forms (CRF) will be provided by the Sponsor.  The term “CRF” as used in this 
protocol may refer to traditional paper CRFs, or electronic case report forms for electronic data 
capture (EDC), as determined by the Sponsor.   
The Investigator may delegate CRF completion to study personnel.  However, the Sponsor must 
be apprised in writing of the name of such persons and the scope of their authority.  The Principal 
Investigator or designee is obligated to review each CRF page and sign or initial the indicated 
pages using ink or for EDC, an electronic signature.  An individual record will be kept for each 
Subject that provided informed consent. 
All entries to a paper CRF should be made clearly in black or dark blue indelible ballpoint pen to 
ensure the legibility of self-copying or photocopied pages. Corrections are made by placing a 
single horizontal line through the incorrect entry, so that the original entry can still be seen, and 
placing the revised entry beside it. The revised entry must be initialed and dated by a member of 
the Investigator’s research team authorized to make CRF entries. Correction fluid must not be 
used. 
CRF entries will be compared to source documents by the study monitor or designated personnel. 
Unless specified otherwise, all information on the CRFs must be traceable to original source 
documents.  
12.2.1 CRF as Source Document 
In this study, the following CRFs may serve as original source documents:     
 
Visual Analog Scale for pain  
 
5-Point Likert for injection force 
 
Demographics/Diabetes History 
 
Subject Questionnaire(s) 
12.2.2 CRF/Data Transmittal  
Instructions for CRF Transmittal will be provided to the Site at Study Initiation. Specific 
procedures may be described in a study-specific Monitoring Plan.    
   
 Data Management and Storage 
Data Management will be performed by the Sponsor.  Data from completed CRFs will be entered 
into a controlled database and the database verified for accuracy against the CRFs, when 
applicable. If electronic data capture is utilized, the electronic records entered at the Site will be 
entered directly into the controlled database.  Data security is ensured through password 
protection, limited access, audit trails, and regular backups of the data. Upon completion of the 

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study and verification of data, data will be screened for accuracy and completeness, after which 
the database will be locked from any additional changes. A copy of the locked database will be 
provided to the GCD Statistics Department for statistical analysis. 
13.0 STATISTICAL METHODS  
Statistical methods will be detailed in a Statistical Analysis Plan. Any deviations from the original 
statistical plan will be justified and described in an amended statistical analysis plan and/or the 
protocol, or in the final statistical report and clinical study report. 
 Sample Size Determination  
Leakage data is currently being used to calculate sample size.   
Based on previous study data (BDT-2P00116) where leakage ≥1.5U was observed in 20/298 
(6.7%) of injections performed with Terumo Nanopass® and in 3/297 (1%) of injections performed 
with BD Nano™ PRO, a simulation was performed (code found in SVN repository under DBC-
18PENDL01\Stat\Sample Size\ Bayesian prior proportion R) indicating that 292 injections per 
each pen needle type would provide 90% power to show BD Nano™ PRO superiority to Terumo 
Nanopass®.  If each Subject tests 6 pairs of pen needles, 292 injections per each pen needle 
requires 49 subjects (rounded to 50 subjects).  50 Subjects will generate data for 600 pen needles: 
300 pen needle pairs; 300 BD Nano™ PRO and 300 Terumo Nanopass®.  A 10% buffer was 
added (to compensate for subject attrition or unusable data), leading to a planned enrollment 
number of 55 subjects.  
Pain:  Assuming the SD for relative VAS is ~50mm (based on DBC-17NUCLS07), a sample size 
of 300 pairs (50 Subjects  6 pairs) has >90% power of passing a -10mm NI criteria, assuming a 
true average of -0.5mm in favor of Terumo Nanopass® (based on a 2-sided 95% CI for the mean). 
 Data Evaluability  
All data collected will be analyzed and reviewed for possible exclusion based on significant 
outliers or protocol deviations. 
Analyses of relative data will only include pairs where both injections were completed. 
 
 Statistical Methods 
Descriptive statistics (number of observations, mean, and standard deviation, minimum and 
maximum) will be calculated and presented for all quantitative responses. Frequency tables with 
number of observations, percentage of total and 95% confidence interval (score method) for the 
percentage (as applicable) will be created for discrete responses.  
Analysis for relative VAS pain:  a two-sided 95% confidence interval will be calculated for the 
average rating.  A modeling approach may be used to adjust for the pair order effect, BD order 
effect within pair (due to the often-observed bias towards favoring the last pen needle used in a 
pair), abdomen site effect and random subject effect.  Results will be tested for non-inferiority, 
followed by superiority:   

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If the lower bound of the CI is > -10mm, we can conclude in non-inferiority 
If the lower bound of the CI is > 0mm, we can conclude in superiority 
 
Analysis for injection force via 5-point Likert scale: the responses will be converted to ratings of -
2 – 2 (where positive ratings favor BD) and a two-sided 95% confidence interval will be calculated 
for the average rating.   A modeling approach may be used to adjust for the pair order effect, BD 
order effect within pair, abdomen site effect and random subject effect.  Results will be tested for 
superiority:   
If the lower bound of the CI is > 0, we can conclude in superiority   
 
Responses will also be converted to 3 categories: favoring Terumo Nanopass® (negative 
ratings), no difference (0 ratings) and favoring BD Nano™ PRO (positive ratings) and the 
difference in percentage of responses with a preference for BD vs Terumo needle calculated, 
adjusting for the “no preference” category.  
 
Analysis for needle bending and leaking:  analysis will be performed using a binary logistic 
regression with random subject effect and fixed pen needle effect, pair order effect, PN order 
effect within pair and abdomen site effect. The average difference in percentage of occurrence 
with BD PN and Terumo PN will be calculated with 95% confidence interval and assessed for 
statistical significance. The upper bound of the confidence interval will be compared to 0:  
superiority will be concluded given that the upper bound of the 95% confidence interval for the 
difference in proportions is < 0%. 
 
Analysis for time to deliver and dwell time:  A mixed effect model will be used (fixed effects of 
pen needle type, abdomen site, order of pair, order of pen needle within pair and random 
Subject effect) to estimate average difference (BD PN – Terumo PN) in time to deliver and dwell 
time.  The upper bound of the confidence interval will be compared to 0:  superiority will be 
concluded given that the upper bound of the 95% interval for the average difference is < 0 
seconds. 
 
Other exploratory endpoints will be summarized. 
 
 Demographics/Other descriptive information 
Demographic variables will be summarized for all subjects in each study group. Count, mean, 
standard deviation, median, min, and max values will be calculated for all continuous variables. 
Count and percentage will be calculated for the categorical variables. Subject disposition will be 
tabulated. 
 
 Safety Analysis 
Data listings will be provided for any adverse event and serious adverse event. Adverse events 
will be summarized descriptively by pen needle and study subgroup. 
 Interim analysis 
No interim analysis is planned under this protocol. 

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 Additional analyses 
No additional analyses planned under this protocol. 
14.0 QUALITY CONTROL AND ASSURANCE 
 Accountability of Study Products 
Investigational study products will be released only for use by Investigators who have obtained 
written IRB/EC approval (as required) for participation in this study, who have completed all 
required study documentation, and who have been qualified by the Sponsor.  Investigators must 
maintain control over all study products, and ensure they are used in accordance with this 
protocol.  Failure to do so may result in the Sponsor suspending or terminating the study at the 
Investigator’s Site.   
The Investigator will ensure that study products are only dispensed to Subjects (or used for 
specimens) properly enrolled in the study. The Investigator must maintain records of receipt, 
disposition, return and/or destruction of all study products. All investigational study products 
released to the Site must be accounted for at the unit level prior to study close out, regardless of 
disposition.  The Study Monitor will regularly review all records regarding study product 
accountability.  
The Sponsor will maintain records that document the shipment, receipt, disposition, return and/or 
destruction of study products.  
 Monitoring  
BD, the study sponsor, will designate trained and qualified personnel to monitor the progress of 
this clinical study in accordance with BD Monitoring SOPs and the study-specific Monitoring Plan.  
A pre-study Site qualification visit will be conducted to assess the adequacy of the Site facilities 
and staff with respect to study requirements.  
Prior to study start, a study initiation visit will be conducted to provide training to Site Staff with 
regard to the protocol, the completion of study documentation and Case Report Forms (CRFs), 
the monitoring schedule, and all regulatory requirements. During the study, routine monitoring 
visits will be conducted to assure the Site continues to adhere to the protocol, the investigator 
agreement, and regulations regarding conduct of clinical studies.  Assessments will be made 
regarding the Subjects’ protection and safety, when relevant, as well as the quality, completeness, 
and integrity of the data. The Study Monitor will assist the investigative Site with query resolution 
and will perform Site close-out activities once all queries have been resolved. 
Additional visits may be carried out depending upon Site activity and performance. The 
Investigator must agree to the inspection of all study related records and give direct access to 
source documents for verification of data on CRFs.  
The Investigator is responsible for ensuring that any Site-owned equipment required for use in 
the study is properly installed and maintained (e.g., inspected, calibrated, alarmed). 
Documentation of equipment maintenance procedures must be available for review by the 
Monitor.   
 Audits and Inspections 
If the study is selected for audit by the Sponsor or if there is an inspection by the appropriate 
Health Authorities, then the Investigator and his team will make themselves available during the 

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visit.  The Investigator must agree to the inspection of all study related records and give the 
auditor/inspector direct access to source documents for verification of data on CRFs.  The 
Subject’s anonymity must be safeguarded and data checked during the audit remain confidential. 
As soon as the Investigator is aware of an upcoming inspection/audit by the Health Authorities, 
he/she will promptly inform BD.  As agreed with the Investigator, BD personnel may be present 
at the Site during the inspection.  
 Protocol Deviations 
Protocol deviations are not permitted and should be implemented prospectively as a protocol 
amendment whenever practical or appropriate, unless required to protect the safety and well-
being of the Subject.  The Investigator must notify the Sponsor immediately of any such deviation 
resulting from the need to protect a Subject.   
Protocol deviations (other than those required to protect the safety and well-being of a Subject) 
may impact the evaluability of study data, and may place Subjects at risk.   If the Investigator or 
their staff inadvertently deviates from the study plan, the Investigator should implement 
appropriate corrective and preventive procedures, and should notify the Sponsor at their earliest 
convenience.  Significant deviations may also need to be reported to the IRB/EC and local health 
authority.   
The Study Monitor will evaluate records of study conduct at the Site to identify any deviations, 
and will also report them to the Sponsor.  Upon evaluation by the Sponsor, actions may be 
required to prevent additional deviations, such as retraining of the Site, implementation of 
additional Site procedures, and more frequent monitoring.  If these steps fail, more serious 
measures, up to and including termination of the Site and withdrawal of study product may be 
necessary.   
15.0 ETHICAL AND REGULATORY STANDARDS  
 IRB/EC  
An appropriate IRB/EC must review this protocol, the Informed Consent Form (if applicable), and 
any other supporting study documents which affect Subject or study personnel safety, prior to 
study initiation at an investigational Site. No investigational Site may begin the study until the 
IRB/EC has given its written approval, signed by the IRB/EC chairperson or authorized personnel, 
and a copy of the approval letter and the approved Informed Consent Form (if applicable) has 
been provided to the Sponsor. 
 Informed Consent 
Prior to giving informed consent, each candidate will have the opportunity to review the study 
procedures, risks and benefits and ask any questions he or she may have regarding the study. 
Before enrollment, each Subject must give informed consent, documented by signing a written 
form, created and approved in compliance with 21 CFR Part 50.25 and 21 CFR Part 56. Each 
Subject should be given a copy of the signed informed consent document.  
 Confidentiality of Data  
Subject confidentiality is strictly held in trust by the participating investigators, their staff, and BD 
and their agents.  This confidentiality is extended to cover testing of biological samples in addition 
to the clinical information relating to participating Subjects.  Subject confidentiality and anonymity 

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will be maintained at all times by removal of all identifiers from any data, clinical samples or 
documentation submitted for this study. 
Any data collected meeting the definition of PHI will be collected and maintained using the 
designated authorizations and following all privacy procedures as specified in the applicable 
health authority regulations.   
BD will maintain the security and confidentiality of all clinical study data sent to BD.  BD clinical 
study databases will not be shared with any third party without the express written consent of the 
Principal Investigator and/or Site. 
The Study Monitor or other authorized representatives of BD may inspect all documents and 
records required to be maintained by the Investigator.  The Site will permit access to such records.  
BD and the Site may be required to provide regulatory agencies access to clinical study data and 
records, as well as source documents. 
All other agreements as to confidentiality by BD, the Principal Investigator, and the Site may be 
found in the Confidential Disclosure Agreement and the Clinical Trial Agreement. 
 Protocol Modifications  
Amendments to the protocol will not be implemented without agreement from the Sponsor and 
prior submission to and written approval from the governing IRB/EC, except when necessary to 
eliminate an immediate hazard to the Subject. Notice of an emergency modification shall be given 
to the Sponsor and the reviewing IRB/EC as soon as possible, but in no event later than 5 working 
days after the emergency occurred. Protocol amendments may affect Informed Consent Forms 
for current and future Subjects. 
Minor changes to the protocol, such as correction of typographical errors or changes in personnel 
names (other than the PI) or contact information will be processed as administrative changes. 
Administrative changes will be submitted to the governing IRB/EC but implementation of the 
administrative change may proceed without prior IRB/EC approval, unless so required by the 
IRB/EC or Site SOPs.  
 Study Discontinuation 
BD reserves the right to temporarily suspend or prematurely discontinue the study at a single Site 
or at all Sites at any time and for any reason.  If such action is taken, BD will discuss the reasons 
with all Investigators (the Investigator).  If the study is terminated or suspended due to safety 
reasons, the Sponsor will inform the health authorities as required, and provide the reason(s) for 
the action.  Investigator(s) must inform their IRB/EC promptly and provide the reason(s) for the 
suspension or termination. 
 Clinical Study Registration  
In compliance with Title VIII of Public Law 110-85, known as FDA Amendments Act of 2007 
(FDAAA), BD will register all applicable studies and disclose study results in a publicly accessible 
database, e.g. the ClinicalTrials.gov web site.  Applicable studies will be registered no later than 
21 days after commencing enrollment.  Study results for applicable studies will be posted to the 
website within 12 months of the last Subject visit for collection of primary outcome data, or after 
health authority approval for previously unapproved devices.  BD has responsibility for 
determining whether this study qualifies as an “applicable” study under the law, and if so, will take 
responsibility for registration and disclosure as required by law. 

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 Publication of Results  
BD believes that results of applicable clinical studies of our products should be published in peer-
reviewed literature in a timely, accurate, complete and balanced manner, regardless of study 
outcomes. BD is committed to making information public whenever it relates to the safety and 
efficacy of its marketed products. 
Any formal presentation or publication of data collected from this study will be considered as a 
joint publication by the investigator(s) and the appropriate personnel of BD. Authorship will be 
based on generally accepted criteria of the ICMJE (International Committee of Medical Journal 
Editors) and determined by mutual agreement. For multi-center studies, the first publication will 
be based on data from all centers, analyzed as stipulated in the protocol by BD statisticians, and 
not based on data from a single Site or a subset of Sites. Investigators participating in multi-center 
studies agree not to present data gathered from one center or a small group of centers before the 
full, initial publication, unless formally agreed to by all other investigators and BD (the sole 
exception being an unanticipated adverse event that is product-related and which might have 
clinically significant safety implications for a marketed product or a class of products). 
BD must receive copies of any intended communication in advance of publication as specified in 
the Clinical Trial Agreement. In a timely manner, BD will review the communications for accuracy 
(thus avoiding potential discrepancies with submissions to health authorities), verify that 
confidential information is not being inadvertently divulged and to provide any relevant 
supplementary information to the investigators. 
 Record Retention 
If the Principal Investigator or Clinical Center withdraws from the responsibility of keeping the 
study records, custody must be transferred to a person or entity who will accept the responsibility.  
BD must be notified in writing of the name and address of the new custodian. 
Federal regulations require that a copy of all essential study documents (e.g., IRB/EC approvals, 
signed informed consent forms, source documents, CRF copies, safety reports, test article 
dispensing records, etc.), must be retained in the files of the responsible Investigator for a 
minimum of 2 years following notification by BD that all investigations are completed, terminated, 
or discontinued, or that the FDA has approved the application (21 CFR 812.140). 
16.0 BIBLIOGRAPHY/REFERENCES 
1. Edwards CL, Fillingim RB, Keefe F. Race, ethnicity and pain. Pain. 2001; 94:133-137. 
2. Watson PJ, Latif RK, Rowbotham DJ. Ethnic differences in thermal pain responses: a 
comparison of South Asian and White British healthy males. Pain. 2005;118:194-200 
3. Palmer B, Macfarlane G, Afzal C, et al. Acculturation and the prevalence of pain amongst South 
Asian minority ethnic groups in the UK. Rheumatology. 2007; 46:1009-1014 
4. O Komiyama, M Kawara, A De Laat. Ethnic differences regarding tactile and pain thresholds in 
the trigeminal region. The Journal of Pain. 2007; 8(4): 363-369. 
5. Mieko M. Beliefs about appropriate pain behavior: cross‐cultural and sex differences between 
Japanese and Euro‐Americans, European Jr Pain. 2012; 9(4): 389-393. 

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17.0 PROTOCOL REVISION HISTORY 
Version # 
Rationale for Change 
Section 
or 
Page affected 
Description of change   
1.0 
New Protocol 
 
 
2.0 
Clarified 
Leakage 
collection 
when blood is at the injection 
site 
 
 
 
 
 
 
 
Corrected typo of TM in title 
Section 6.2.1 
 
 
Section 13.2 
 
 
Section 18.6  
Updated language to insure leakage was 
collected from PN tip, if there was blood 
at injection site 
 
Removed that if blood was observed that 
the sample would not be included in the 
data analysis 
 
Updated leakage procedure 
3.0  
Sutter 
Health 
has 
safety 
concerns 
on 
re-using 
the 
ClikSTAR® Insulin Reusable 
Pen for more than one subject.  
Section 5.0  
and 
Section 6.2.1 
 
A new ClikSTAR® Insulin Reusable Pen 
will be used for each subject. 
4.0 
Revised protocol introduction to 
justify use of study population 
 
 
Clarified exclusion criteria for 
subject PN 
 
 
 
Give sites the option provide 
each subject with either a new or 
cleaned 
ClikSTAR® 
Insulin 
Reusable Pen 
 
 
Section 1.0 
 
 
Section 4.2e 
 
 
 
Section 5.3 
 
 
 
 
 
Revised protocol introduction to include 
justification for study population and 
inclusion criterion  
 
Updated exclusion to allow site staff to 
confirm the pen needle the subject is 
currently using via medical record or 
pharmacy. 
 
 
Either a new or cleaned ClikSTAR® 
Insulin Reusable Pen will be used for 
each 
subject 
depending 
on 
site 
preference. See Appendix 18.3 for Pen 
Cleaning Procedure) 
 
 

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Version # 
Rationale for Change 
Section 
or 
Page affected 
Description of change   
Clarified the two times that Site 
Staff will record during needle 
injection  
 
 
 
 
 
Updated introduction to cleaning 
procedure section   
 
 
Update 
Medical 
Affairs 
signature and remove Marketing 
signature 
 
Section 6.2.1 
 
 
 
Section 16.0 
 
Section 16.3 
 
 
Sponsor 
Approval 
Section 
Total injection time will be recorded by 
Site Staff.  The time from injection button 
fully depressed to the removal of needle 
from body will be calculated by Sponsor  
 
 
References added  
 
 
Added more detail on steps involved in 
pen cleaning procedure  
 
 
Changed MA representative to Shahista 
Whooley and deleted Marketing 
approval which is no longer needed. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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18.0 APPENDICES 
18.1: Gravimetric Leakage Quantification Procedure 
 
Quantification of Liquid from Pen Needle and Skin Surface after Administration  
 
Study Staff preparing and handling plastic tubes and eye spears must do so with gloved hands to 
prevent transfer of oils from hands to the assembly. Tubes are to be pre-weighed in the morning 
of the day of use. 
 
Materials: 
• 
Cellulose Spears  
• 
Analytical Balance  minimally accurate to 0.000 gm 
• 
Plastic Falcon tubes (to hold spears)  
 
Procedure: 
1. Label (number) a set of plastic tubes.  
 
2. Arrange empty, uncapped tubes in test-tube rack and place one spear in each tube, replace 
caps securely on tubes.   
3. Zero the Balance.  Balance should be placed in an area with limited activity to avoid vibration. 
4. Pre-weigh tube with spear by placing on the scale vertically (resting on its cap). Tubes will be 
pre-weighed in the morning of the day of use.  
5. Record the dry weight on the appropriate data collection form (pre (dry)-weight). 
6. Collect fluid from skin and needle tip using the pre-weighed absorbent spear.  Do not collect 
fluid from skin if bleeding 
7. Immediately replace spear into tube, replace cap securely and as soon as possible weigh the 
tube by placing on the scale vertically (resting on its cap) or place in pre-weighed beaker. 
8. Record wet weight on the data collection form (post (wet)-weight). 
9. Discard tube with eye spear. 
  
 
 
 

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 Needle Bending Evaluation 
 
The Study Staff will visually determine if the pen needle is bent.  If bent, staff will measure and document 
needle bending using the provided scale.  Post bend scoring, pen needle will be disposed of as 
appropriate.   
Cannula bend scale (example): 
 
 
Degree of Bend 
Score 
0° (no bend) 
0 
> 0° to 10° 
1 
>10° to 20° 
2 
> 20° to 30° 
3 
> 30° to 40° 
4 
> 40° 
5 
 
 
 

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18.3 Pen Cleaning Procedure 
In this study there is minimal risk of transmission of any pathogens through skin contact, as the pen is 
only in contact with the patient’s hands.  The pens will be cleaned using the procedure described below 
after each use using hospital grade bleach-based disinfectant wipes.  Any pens contaminated with blood 
will not be re-used and will be discarded in the appropriate container for destruction.  
 
 
The following cleaning procedure will be performed by Study Staff between each Subject use:  
 
Cleaning the pens is to be completed using hospital grade disinfectant wipes 
 
Gloves should be worn while completing this cleaning procedure  
 
Clean the pens by wiping all surfaces of the pen with disinfectant wipe. Care is to be exerted that 
no lint or other particles are left behind during the process. 
o Use fresh disinfectant wipe for each pen. Discard wipe after each use.  
o Air dry the pens for about one minute.