Nucleus Claims Study: Evaluating the User Performance and Experience of Nucleus Pen vs. Commercially Available Pen Needle
Phase: NA
Conditions: Diabetes
Sponsor: Becton, Dickinson and Company

Corporate Clinical Development 
CCD-5115.T01 Protocol Template  
Revision 05 
 
Page 1 of 30 
BD Protocol #: DBC-17NUCLS07 
Protocol Title: Nucleus Claims Study: Evaluating the User Performance 
and Experience of Nucleus Pen vs. Commercially Available 
Pen Needle 
Current Version Version 5.0 December 20, 2017 (Amendment 4) 
Version History 
 
Version 1.0 August 7, 2017 (Original) 
Version 2.0 August 18, 2017 (Amendment 1) 
Version 2.1 August 24, 2017 (admin change) 
Version 2.2 August 25, 2017 (admin change) 
Version 3.0 September 28, 2017 (Amendment 2) 
Version 4.0 October 20, 2017 (Amendment 3) 
Version 4.1 October 30, 2017 (admin change) 
Sponsor Becton, Dickinson, and Company 
BD Medical – Diabetes Care 
1 Becton Drive 
Franklin Lakes, NJ 07417 
Sponsor Medical 
Monitor 
 
Laurence Hirsch, Worldwide Vice President, Medical Affairs 
BD Diabetes Care  
Office #: 201-847-6518 
Mobile #: 908-715-9159 
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 
This document is signed 
electronically in the 
eTMF system 
 
Medical Monitor 
Laurence Hirsch, 
MD  
This document is signed 
electronically in the 
eTMF system 
 
Study Statistician 
Rianka Bhattacharya 
This document is signed 
electronically in the 
eTMF system 
 
Study Manager 
Lydia Blank 
This document is signed 
electronically in the 
eTMF system 
 
Business Unit 
Medical Director  
Brian K. Pflug  
This document is signed 
electronically in the 
eTMF system 
 
 

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BD CONFIDENTIAL  
 
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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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Table of Contents  
LIST OF ABBREVIATIONS AND DEFINITION OF TERMS ................................................... 6 
1.0 
INTRODUCTION .............................................................................................................. 7 
2.0 
OBJECTIVES ..................................................................................................................... 7 
2.1 
Primary Objectives .............................................................................................................. 7 
2.2 
Secondary Objectives .......................................................................................................... 7 
2.3 
Exploratory Objectives ........................................................................................................ 7 
3.0 
STUDY DESIGN................................................................................................................ 8 
3.1 
Overall Study Design .......................................................................................................... 8 
3.2 
Specification of Study Endpoints ...................................................................................... 10 
3.3 
Acceptance Criteria ........................................................................................................... 11 
3.4 
Treatment Allocation and Methods to Reduce Bias .......................................................... 11 
3.5 
Stopping Rules .................................................................................................................. 11 
4.0 
STUDY POPULATION ................................................................................................... 11 
4.1 
Inclusion Criteria ............................................................................................................... 11 
4.2 
Exclusion Criteria .............................................................................................................. 12 
5.0 
DESCRIPTION OF STUDY PRODUCTS ...................................................................... 13 
5.1 
Test Product(s) .................................................................................................................. 13 
5.2 
Reference Products (Commercially Available Product) ................................................... 13 
5.3 
Ancillary Products (if applicable) ..................................................................................... 13 
5.4 
Product Labeling ............................................................................................................... 13 
5.5 
Maintenance and Storage of Study Products ..................................................................... 14 
6.0 
STUDY METHODS ......................................................................................................... 14 
6.1 
General Methods ............................................................................................................... 14 
6.2 
Visit 1: Screening and Enrollment .................................................................................... 14 
6.3 
Wash-in Visit (Wash-in users only) .................................................................................. 15 
6.4 
Visit 2 and 3 ...................................................................................................................... 15 
7.0 
INTERRUPTION OR DISCONTINUATION OF PARTICIPATION/TESTING .......... 16 
7.1 
Discontinuation of Study Subjects .................................................................................... 16 
7.2 
Discontinuation Visits and Follow-up Procedures ............................................................ 16 
8.0 
RISK / BENEFIT ASSESSMENT ................................................................................... 16 
8.1 
Potential Risks ................................................................................................................... 16 
8.2 
Potential Benefits .............................................................................................................. 17 
9.0 
SAFETY ........................................................................................................................... 17 
9.1 
Adverse Event Definitions ................................................................................................ 17 
9.2 
Adverse Event (AE) Management..................................................................................... 18 
9.3 
Assessment of Adverse Events (AEs) ............................................................................... 19 
9.4 
Additional Procedures for Assessing & Reporting Serious Adverse Events (SAE) ......... 19 
10.0 
INCIDENTS ..................................................................................................................... 20 
11.0 
RETURN OR DESTRUCTION OF STUDY PRODUCT ............................................... 21 

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11.1 
Defective or Failed Study Products ................................................................................... 21 
12.0 
DATA COLLECTION AND MANAGEMENT .............................................................. 21 
12.1 
Source Documents ............................................................................................................. 21 
12.2 
Case Report Forms (CRF) ................................................................................................. 22 
12.3 
Data Management and Storage .......................................................................................... 23 
13.0 
STATISTICAL METHODS ............................................................................................. 23 
13.1 
Sample Size Determination ............................................................................................... 23 
13.2 
Data Evaluability ............................................................................................................... 23 
13.3 
Statistical Methods ............................................................................................................ 23 
13.4 
Demographics/Other descriptive information ................................................................... 24 
13.5 
Safety Analysis .................................................................................................................. 24 
13.6 
Interim analysis ................................................................................................................. 24 
13.7 
Additional analyses ........................................................................................................... 24 
14.0 
QUALITY CONTROL AND ASSURANCE .................................................................. 24 
14.1 
Accountability of Study Products ...................................................................................... 24 
14.2 
Monitoring ......................................................................................................................... 25 
14.3 
Audits and Inspections ...................................................................................................... 25 
14.4 
Protocol Deviations ........................................................................................................... 25 
15.0 
ETHICAL AND REGULATORY STANDARDS ........................................................... 26 
15.1 
IRB/EC .............................................................................................................................. 26 
15.2 
Informed Consent .............................................................................................................. 26 
15.3 
Confidentiality of Data ...................................................................................................... 26 
15.4 
Protocol Modifications ...................................................................................................... 27 
15.5 
Study Discontinuation ....................................................................................................... 27 
15.6 
Clinical Study Registration ............................................................................................... 27 
15.7 
Publication of Results ........................................................................................................ 27 
15.8 
Record Retention ............................................................................................................... 28 
16.0 
BIBLIOGRAPHY/REFERENCES................................................................................... 28 
17.0 
PROTOCOL REVISION HISTORY ............................................................................... 28 
18.0 
APPENDICES .................................................................................................................. 30 
 
 
 

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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 
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 
lbf 
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 
 
 

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1.0 
INTRODUCTION 
From a market research study (Van Gogh; 2013) – the results showed that User’s perception could not differentiate 
BD pen needles from other competitors.  Therefore, the pen needle market is currently being driven primarily by 
cost. This study will be used to support the business replacement strategy for BD’s current 4mm pen needle. A 
design improvement is being implemented by introducing a flatter hub (base) by eliminating the post on the hub. 
This study is designed to assess the User’s experience and preference and outcomes are intended to be used for 
marketing claims.  This study will have four study groups based on commercially available 32G pen needle groups:  
1) BD Nano, 2) NovoFine, 3) NovoFine Plus & NovoTwist and 4) Other 32G (such as UltiMed, MHC, or other 
private label). 
2.0 
OBJECTIVES 
2.1 Primary Objectives 
For all study groups combined, compare user preference for the BD Nucleus pen needle vs. current 
commercially available pen needles. 
2.2 Secondary Objectives 
For each individual study group, compare user preference for the BD Nucleus pen needle vs. current 
commercially available pen needles. 
For all study groups combined and each individual study group, compare the user experience with the BD 
Nucleus pen needle and the commercially available pen needles for component preference. 
a. Outer Cover Handling 
b. Inner Shield Handling 
c. Hub Comfort 
For all study groups combined and each individual study group, compare the user experience with the BD 
Nucleus pen needle and the commercially available pen needles for the following: 
a. Overall Comfort 
b. Anxiety Associated with a Needle Stick Injury 
c. Injection Pain 
d. Bruising 
e. Bending 
f. Ease of Use 
g. Leakage from this injection site 
2.3 Exploratory Objectives 
For all study groups combined, assess the user acceptance for the following items for the pen needle (non-
comparative): 
a. Teardrop Label Removal Force 
b. Outer Cover Removal Force 
c. Inner Shield Removal Force  
d. Ease of Insulin Delivery 
 
In addition, Pen Needle breakage will be monitored (all groups combined). 
 

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A sub-group with Asian ethnicity, all study groups combined, will also be evaluated for the 
objectives listed in the Primary and Secondary Objectives. 
3.0 
STUDY DESIGN 
3.1 Overall Study Design 
This is a multi-site, prospective, open-label, randomized, 2-period crossover (15 days per period) study 
comparing commercially available 32G pen needles to the BD Nucleus pen needle. Nucleus pen needle will 
be compared to four groups of pen needles: 1) BD Nano (32Gx4mm), 2) NovoFine (32Gx6mm), 3) 
NovoFine Plus (32Gx4mm) & NovoTwist (32Gx5mm) and 4) Other 32G (such as UltiMed, MHC, or other 
private label). Approximately 25% of the subjects are expected to be Type 1 patients and the remaining 
75% are expected to be Type 2 patients.  
The study is targeting 260 subjects. A total of 240 evaluable subjects are needed with an additional 20 
subjects for subjects lost to follow up or other significant protocol deviations. Each group will consist of 
approximately 60 subjects. Each subject will be screened to determine eligibility into the study. Subjects 
entering the study who are currently injecting with one of the above mentioned pen needles will 
automatically be enrolled in their respective group. For example, if a subject comes in using the BD Nano, 
they will be enrolled in Group 1. If their current pen needle group has completed enrollment, they will be 
eligible for wash-in (see below). 
To facilitate recruitment, a 14 day wash-in period will be allowed in the following situations: 
 
As BD holds the vast majority of the Pen needle market share in the US, enrolling subjects using non 
BD brands will be difficult.  Subject’s currently using a 32G pen needle of 4, 5 or 6 mm lengths will 
be allowed to wash-in if their current pen needle group has completed enrollment of 60 evaluable 
subjects. These subjects will be eligible to wash-in to the next available applicable group, per the Wash-
In randomization schedule. The length of their current pen needle will be maintained. 
 
For subject’s currently using a 31G pen needle of 4, 5 or 6 mm lengths provided the subject is willing 
to switch to an assigned commercially available 32G pen needle for the duration of the study. These 
subjects will be eligible to wash-in to an available applicable group, per the Wash-In randomization 
schedule. The length of their current pen needle will be maintained.  
 
Wash-in subjects will be randomized as follows: 
 
If subject is currently on a 31G x 4mm or 32G x 4mm they will get randomized to either 
Group 3 (Novo Fine Plus (32Gx4mm) or Group 4 (UltiCare Micro 32Gx4mm). 
 
If subject is currently on a 31G x 5mm or 32G x 5mm, they will randomized to either Group 
3 (NovoTwist (32Gx5mm)) or Group 4 (MHC Easy Touch 5mm x 32G). 
 
If subject is currently on a 31G x 6mm or 32G x 6mm, they will randomized to either Group 
2 (Novo Fine  (32Gx6mm)) or Group 4 (Simple Diagnostics Comfort EZ 6mm x 32G). 
Please refer to the Wash-in randomization schedule. 
 
Subjects who will remain on their current 32G pen needle will be required to visit the site a total of three 
times. Wash-in subjects will have an additional visit (Wash-in Visit) for a total of 4 visits. (see Subject 
Flow Chart Diagram 1).  

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The study will consist of two 15 day periods (+/- 3 days, no fewer than 13 days and no more than 17 days) 
in which the subject will use each pen needle (BD Nucleus pen needle or Commercially available 32G pen 
needle, order randomized) for injection. 
Results will be compared to address the Primary, Secondary and Exploratory objectives. A final report will 
be issued summarizing all outcomes and conclusions. 
Diagram 1 Subject Flow Chart
 

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3.2 Specification of Study Endpoints 
3.2.1 
Primary Endpoints 
Preference: At the end of the last study period, each subject will be asked to evaluate his or her 
perception using a 150mm relative VAS scale.  The question “Which pen needle did you prefer 
overall?” will be asked. The far left (-75mm) of the scale will be labelled “Period 1 pen needle was 
strongly preferred overall”. The 0mm center point will be labelled “No Preference”. The far right 
(+75mm) of the scale will be labelled “Period 2 pen needle was strongly preferred overall”. 
 
 
 
3.2.2 
Secondary Endpoints 
At the end of the last study period: Each subject will be asked to evaluate his or her perception using a 
150mm relative VAS scale for each of the following endpoints: Overall Comfort, Anxiety Associated with 
a Needle Stick Injury, Injection Pain, and Ease of Use.  
 
 
After each injection: Additional secondary endpoints information will be collected for Bruising, 
Needle Bending/Breaking and Leakage in the Subject Diary. 
 
For Needle Breaking, Bending or Injection Site Bleeding or Bruising, each subject will evaluate 
his/her perception of each by answering with a yes or no response. 
For needle leakage, each subject will record leakage using the following scale (0-5): 
0
1
2
3
4
5
0 µL
1 µL
10 µL
20 µL
50 µL
35 µL
mm
Droplet example
Droplet volume
size
mm scale
 
3.2.3 
Exploratory Endpoints 
At the end of each study period, each subject will evaluate his or her perception of each of the following by 
answering with a yes or no response. 
Teardrop Label Removal Force: The subject will be asked “Did you find the teardrop label easy to 
remove?” The response options will either be Yes or No. 
 
Outer Cover Removal Force: The subject will be asked “Did you find the outer cover easy to 
remove?” The response options will either be Yes or No. 
 
Inner Shield Removal Force: The subject will be asked “Did you find t the inner shield easy to 
remove?” The response options will either be Yes or No. 
 
Period 1 pen needle was 
strongly preferred overall 
No Preference 
Period 2 pen needle was 
strongly preferred overall 

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Ease of Insulin/Non-insulin Delivery: The subject will be asked “Were you able to deliver the 
insulin/non-insulin easily?” The response options will either be Yes or No. 
3.2.4 
Safety Endpoints 
At 2nd and 3rd visits, presence and severity of any adverse events will be evaluated, recorded, and 
followed up as required. 
For a complete list of survey questions, please refer to “Form: Questionnaire”. 
3.3 Acceptance Criteria 
Primary Objective:  Non-Inferiority Criterion (based on relative VAS where -75mm indicates a strong 
preference for Period 1 pen needle and +75mm indicates a strong preference for Period 2 pen needle) is -
10mm.    
Secondary Objectives:  
For Overall Comfort, Anxiety Associated with a Needle Stick Injury, Injection Pain, and Ease of Use the 
Non-Inferiority Criterion is also -10mm.    
For Needle Breaking, Needle Bending, Injection Site Bleeding, Bruising and Leakage Score > 1: The 
difference in occurrence rate with BD Nucleus pen needle vs Occurrence rate with Current pen needle will 
be compared to a 4% non-inferiority (NI) criteria.   
Exploratory Objectives: No formal acceptance criteria has been established for this study.  
3.4 Treatment Allocation and Methods to Reduce Bias  
The order of the pen needle type (current vs. Nucleus) will be randomized for each subject. There will be 
no masking or blinding in this study. 
3.5 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 
Approximately 260 subjects that are currently injecting, using a pen injector and pen needle: 
o Insulin only 
o Non-insulin injectable only (a minimum of once a day) 
o Both-Insulin and a non-insulin injectable medication 
A total of 240 evaluable subjects are needed to complete the study. A goal of 60 subjects per group (for 
90% power) is targeted. Subjects may also be injecting other diabetes medications with a pen needle and 
pen device. If subjects use the same pen needle to inject both insulin and non-insulin medications, they will 
be asked to use the Nucleus product for both injections during the study. If subjects do not use the same 
pen needle to inject both insulin and non-insulin injectable medications, they will be asked to only use the 
medication (either insulin or non-insulin) with which they use one of the eligible pen needles. 
4.1 Inclusion Criteria 
Male and female patients will be considered for participation in the study if they fulfill the following 
conditions:  

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a. Adults (18 – 75 inclusive)  
b. Diagnosed Type 1 or Type 2 diabetes 
c. Every effort will be made to recruit approximately 25% Type 1 patients (of the total 
population, not of each subgroup) (minimum: 10%, maximum: 50%) 
d. Every effort will be made to recruit a minimum of 30 subjects with Asian ethnicity (of the 
total population, not of each subgroup).  Ideally, 60 Asian subjects are needed for the study. 
e. Minimum within the last 4 months experience self-injecting insulin and/or non-insulin with 
a pen injector 
f. Minimum within the last 2 months experience self-injecting consistently with one of the 
following available pen needles OR a subject may be enrolled that is using a 31G/32G pen 
needle that is not longer than 6mm in length who is willing to transfer to one of the following 
32G pen needle with a 14 day wash-in period: 
i. Group 1: BD Nano 32Gx4mm 
ii. Group 2: NovoFine 32Gx6mm 
iii. Group 3: NovoTwist 32Gx5mm or 
iv. Group 3: NovoFine Plus 32Gx4mm 
v. Group 4: Owen Mumford PenTips 32Gx4mm or 
vi. Group 4: Perrigo / Ypsomed ClickFine 32Gx4mm or 
vii. Group 4: Other 32G such as UltiMed, MHC, or other private label. 
 
g. Able and willing to provide informed consent/participant form 
h. Able and willing to complete all study procedures 
 
4.2 Exclusion Criteria 
Subjects with any one of the following characteristics will be excluded from participation in this study: 
a. Self-injecting with a pen injector for less than 3 months 
b. Planned changes in diabetes medication regimen (increasing or decreasing number of 
injections per day). 
c. Positive pregnancy test (self-attestation)   
d. Currently taking anti-platelet therapy or anticoagulants (Use of up to 81 mg per day of aspirin 
is permitted).  
e. History of a bleeding disorder or easy bruising 
f. Blood borne infection(s) 
g. History of recurrent dermatological conditions or skin disorder (e.g., psoriasis, eczema)  
h. Gross skin anomalies and abnormalities (e.g., scars, stretch marks, discolorations, tattoos, 
superficial masses, acne, inflammation) located at or very close to the injection sites  
i. 
Fear of needles, history of symptomatic low blood pressure or history of fainting (syncope) 
during hypodermic injections.   

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j. 
Use of any prescription analgesic medications within 24 hours of first study injection, and 
during the study. 
k. 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. 
l. 
Currently participating in another study 
m. Employed by, or currently serving as a contractor or consultant to BD or any diabetes 
injectable medication, insulin pen, or insulin pen needle manufacturer 
5.0 
DESCRIPTION OF STUDY PRODUCTS 
5.1 Test Product(s) 
o BD Nucleus pen needle – 4mm x 32G  
5.2 Reference Products (Commercially Available Product) 
o BD Nano 32Gx4mm 
o NovoFine 32Gx6mm 
o NovoTwist32Gx5mm 
o NovoFine Plus 32Gx4mm 
o Owen Mumford PenTips 32Gx4mm 
o Perrigo / Ypsomed / ReliOn ClickFine 32Gx4mm 
o Other 32Gx4, 5 or 6 mm:  UltiMed, MHC, or other private label   
5.3 Ancillary Products (if applicable)  
Insulin/Non-insulin injectable pens that are compatible with reference pen needles.  
 
5.4 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 unit label, at minimum on its immediate package must 
indicate “For Investigational Use only”, with full statement on the outer packaging. 
For 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” 
Commercial products will be supplied as labeled by the manufacturer.  

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5.5 Maintenance and Storage of Study Products 
All pen needles should be stored according to the manufacturer’s instructions. Refer to section 11.0 of the 
protocol for additional instructions regarding product disposition during and upon study completion (e.g., 
disposal, return or destruction, defective products). 
6.0 
STUDY METHODS 
6.1 General Methods 
This study will include up to 260 Type 1 and Type 2 diabetic subjects with Type 1 comprising of 24-130 subjects 
to the tested population.  An effort will be made to recruit a minimum of 30 Asian descent to be included in the 
tested population. All subjects must be currently using an insulin/non-insulin injectable pen.  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. 
Subjects may be using medication pens for non-insulin injections such as GLP-1 agonists. Subjects may use both 
of these pens in the study, provided they use the same eligible pen needle for both injections. In the study, subjects 
will use the commercially available pen needle for 15 days and the Nucleus pen needle for 15 days, with the 
crossover period order depending on the randomization schedule. As the study progresses, restrictions may be 
placed on number of injections/day. 
6.2 Visit 1: Screening and Enrollment 
Prior to screening subjects for eligibility for the study, the PI or designee must obtain written informed 
consent from all potential subjects. Once consented, subjects will be assigned a subject number.  
The following will be conducted by Site Staff to determine eligibility and to collect 
background/demographical information: 
 
6.2.1 
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 and diabetes history (Type 1 or Type 2, medications including 
dose and methods of delivery).  
6.2.2 
Proficiency: Subjects will be asked to perform a mock injection into an injection pad using a 
BD Nano pen needle.  This will demonstrate their proficiency in injecting with a pen needle 
and pen device. If the subject is unable to demonstrated proficiency, s/he is discontinued from 
the study. The study staff will use a checklist to qualify the subject.  
6.2.3 
Randomization: After each subject has completed the proficiency test, the subject will be 
assigned a randomization number based on their pen needle group (Group 1-4), which will 
determine the order of the pen needed used in Period 1 or Period 2.  
 
 

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6.2.4 
Visit 1 
Non Wash-in Users 
 
Subjects will be randomized to Nucleus pen needle for the first 15-day period, then assigned 
commercial 32G pen needle for the second 15-day period OR assigned to commercial 32G pen 
needle for the first 15-day period, then the Nucleus pen needle for the second 15-day period (See 
randomization schedule). 
 
Subject will be instructed to use only the assigned pen needle during Period 1. If the subject is 
assigned to the Nucleus pen needle, they will be provided enough of the assigned pen needles 
until their scheduled return visit of 15-days. If the subject is assigned to the commercial 32G pen 
needle, they will use their current pen needle until the scheduled return visit of 15 days. 
 
Subject will be given a Diary 1 log to report events and answer questions during Period 1.  
Subjects will be trained on diary documentation.  
 
Wash-in Users 
 
Subjects will be assigned a wash-in randomization number to determine their pen needle group 
(Group 1-4). 
 
Subjects will be instructed to use only the assigned pen needle during the Wash-in Period.  
 
Subjects will be provided enough of the assigned pen needles for Wash-in Period until their 
scheduled return for Wash-in visit in 14 days +/- 2. 
6.3 Wash-in Visit (Wash-in users only, See Section 3.1 for Wash-in Eligibility Criteria) 
 
Wash-in Visit (14 days +/- 2 days from Visit 1) 
 
Subjects will be randomized to Nucleus pen needle for the first 15-day period, then assigned to 
commercial 32G pen needle for the second 15-day period OR assigned to commercial 32G pen 
needle for the first 15-day period, then the Nucleus pen needle for the second 15-day period (See 
randomization schedule). 
 
Subject will be instructed to use only the assigned pen needle during Period 1. Subjects will be 
provided enough of the assigned pen needles, regardless of whether they are randomized to 
Nucleus first or commercial 32G pen needle first, until their scheduled return visit of 15-days.  
 
Subject will be given a Diary 1 log to report events and answer questions during Period 1. 
Subjects will be trained on diary documentation.  
6.4 Visit 2 and 3 
Non Wash-in Users: Visit 2 (15 days+/- 3 days from Visit 1, no fewer than 13 days and no more than 
17 days): 
Wash-in Users: Visit 2 (15 days+/- 3 days from Wash-in visit, no fewer than 13 days and no more than 
17 days): 
 
Diary will be collected and checked for completeness, and any clarifying questions will be asked. 
Study staff will review with subject all AEs, if applicable. 
 
Subject (Non-comparative) questionnaire will be completed by subject evaluating experience 
with assigned pen needle for Period 1. 
 
Subject will be instructed to use only the assigned pen needle during Period 2. If the subject is 
assigned to the Nucleus pen needle, they will be provided enough of the assigned pen needles 
until their scheduled return visit of 15-days. If the subject is assigned to their current pen needle, 

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they will use their current pen needle until the scheduled return visit of 15 days. If the subject is 
an individual who washed-in and is assigned to a new commercially available 32G pen needle, 
they will be provided enough of the assigned pen needles until the scheduled return visit of 15 
days. 
 
Subject will be given a Diary 2 log to report events and answer questions during Period 2. 
 
Visit 3 (15 days +/- 3 days from Visit 2, no fewer than 13 days and no more than 17 days) 
 
Diary will be collected and checked for completeness, and any clarifying questions will be asked 
by PI or designee. Study staff will review with subject all AEs, if applicable. 
 
A non-comparative questionnaire will be completed by each subject evaluating experience with 
assigned pen needle for Period 2.  
 
A comparative questionnaire will be administered comparing the pen needles from the two 
periods. 
7.0 
INTERRUPTION OR DISCONTINUATION OF PARTICIPATION/TESTING  
7.1 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. 
7.2 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. 
8.0 
RISK / BENEFIT ASSESSMENT  
8.1 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 compared with current standard of care, experienced by the study subject. 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) and the procedures being used in disinfecting the 
skin prior to inserting the pen needle these risks are negligible. 

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Risks associated with a pen needle injection may include: 
• 
Discomfort or pain 
• 
Fainting 
• 
Bleeding 
• 
Bruising 
• 
Redness 
• 
Infection 
8.2 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 insulin/non-insulin pen needle, and thus may 
improve medical care for persons with diabetes. 
9.0 
SAFETY 
9.1 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 
 
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. Refer to Protocol Section 
8.1 (Potential Risks) for a list of anticipated adverse events, signs or symptoms. (21CFR-812.3(s)) 

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9.2 Adverse Event (AE) Management 
At each study contact, subjects will be questioned in an open-ended manner regarding any new or worsening 
undesirable signs or symptoms they may have experienced since the previous contact.  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 
 
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 must be considered AEs and documented on the Adverse Event CRF. 
Some signs and symptoms are inherent to the conditions under study (i.e. diabetes) and are likely to occur 
transiently for nearly all subjects in this study. Episodes of hyperglycemia and hypoglycemia occurring 
after subject enrollment and exposure to study product and/or study procedures, should be reported based 
on the following criteria: 
 
All blood glucose values <50 mg/dL (hypoglycemia) or >400 mg/dL (hyperglycemia) that require 
3rd party (defined as, assistance of another person to administer carbohydrates or glucagon) or 
medical assistance for recovery will be recorded as an AE and assessed for seriousness. 
 
Any self-identified hypoglycemia or hyperglycemia without a BG reading or with any BG 
reading that requires 3rd party or medical assistance for recovery will be recorded as an AE and 
assessed for seriousness. 
 
BG >400 mg/dL (and no symptoms of ketosis) will not be considered an AE. 
o 
Signs of ketosis are elevated BG along with nausea but individual has the ability to drink 
fluids and nausea is resolved with additional insulin and oral fluids, this may be 
considered an AE per the discretion of the PI or designee. 
All blood glucose values <50 mg/dL, or self-identified as hypoglycemia that resolves with standard 
carbohydrate administration will not be recorded as an AE unless otherwise determined by the Principal 
Investigator. 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 PI, or the event meets the criteria for a Serious 
Adverse Event (SAE). 

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9.3 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: 
 
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 
9.4 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 Fax Line: (US) 1-201-847-5688 
 
Safety Email:  BD_Trial_Safety@BD.com 
Medical questions about study safety issues and serious adverse events can be directed to the Sponsor 
Medical Monitor. 

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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.  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, 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 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  
All disposable, used products not failed, damaged or otherwise involved in an Incident or Adverse Event are to be 
discarded into appropriate waste containers at the investigational site. 
Unless instructed otherwise by BD, the Investigator will return all remaining 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, MC 250 
Franklin Lakes, NJ 07417 
201-847-4688 
11.1 
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 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  
12.1 
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.  
12.2 
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 will serve as original source documents:    Visual Analog Scale for 
preference, component preference, overall comfort, anxiety, pain, bruising, bending and ease of use. A 
questionnaire will be used for exploratory outcomes.  
 
Demographics/Diabetes History 
 
Diary:  
o Injection Log (Leakage, Bruising, Bleeding, Needle Bending, Needle 
Breaking) 
o AEs 
o Product Issues 
 
Subject (Non-comparative) Questionnaire 
 
Comparative Questionnaire 
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.    
Instructions for CRF Transmittal will be provided to the Investigator at Study Initiation. Specific 
procedures may be described in a study-specific Monitoring Plan.    

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12.3 
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 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 BD Corporate 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 the final 
statistical and study report. 
13.1 
Sample Size Determination  
Based on previous studies, SD for relative VAS is assumed to be ~35mm.  A sample size of 60 subjects has 
90% power of passing a 10mm NI criteria, assuming a true average of 5mm in favor of Nucleus (2-sided 
95% CI for the mean).  A sample size of 45 subjects is sufficient to provide 80% power.  These sample size 
apply to each subgroup for which a NI (or superiority) claim is desired. 
13.2 
Data Evaluability  
All data collected will be analyzed, subject to review for possible exclusion based on significant protocol 
deviations (e.g. failure to follow randomization scheme). 
13.3 
Statistical Methods 
All analyses will be performed and presented per subgroup (Group 1 – Group 4) first (with no alpha 
adjustment).  For each response, a statistical test will be applied to determine whether it is valid to combine 
the results from the four study group into one overall result.  If significant differences between the groups 
are identified, combined results will only include results from the groups exhibiting no significant 
difference; groups that are significantly different (if any) will not be grouped into the overall result.      
If a sufficient number of subjects having a two-weeks wash-in period, are enrolled in the study, a 
comparison of the responses may be performed. The comparison will be conducted between the subjects 
who did wash-in and those who did not wash-in  for all groups pooled together. 
Descriptive statistics (number of observations, mean, standard deviation, minimum, maximum and 95% 
mean confidence interval) 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:  For each outcome measured on a relative VAS, a two-sided 95% confidence 
intervals will be calculated for the average rating.  A modeling approach may be used to adjust for the visit 
effect (because of the often observed bias towards favoring the last PN used).  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 needle breaking, needle bending, injection site bleeding, and bruising:  A 95% confidence 
interval for the following difference in two independent proportions will be calculated using the score 
method: 
 
Proportion with BD Nucleus PN – Proportion with Current PN 
 
The upper bound of the confidence interval will be compared to the 4% NI criterion:  non-inferiority will 
be concluded given the upper bound of the 95% score interval for the difference in proportions is < 4%. 
 
Analysis for needle leakage:  Distribution of leakage scores will be provided and proportion of injections 
with recorded leakage score > 1 will be calculated per pen needles in each subgroup.  Same analysis as 
for needle breaking, needle bending, injection site bleeding or bruising will be performed using 
proportion of injections with recorded leakage score > 1 as the response. 
Exploratory endpoints will be summarized with proportion of “Yes” answers and 95% score confidence 
interval. 
 
13.4 
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 the continuous variables. Count and 
percentage will be calculated for the categorical variables.  
Subject disposition will be tabulated. 
 
13.5 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. 
 
13.6 
Interim analysis 
None planned. 
13.7 
Additional analyses 
None planned. 
14.0 
QUALITY CONTROL AND ASSURANCE 
14.1 
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 

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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.  
14.2 
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.   
14.3 
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 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.  
14.4 
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.   

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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  
15.1 
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. 
15.2 
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 enrolment, 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.  
15.3 
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 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. 

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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. 
15.4 
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.  
15.5 
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. 
15.6 
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. 
15.7 
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 single 
sites 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). 

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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. 
15.8 
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 
None  
17.0 
PROTOCOL REVISION HISTORY 
Version # 
Rationale for Change 
Section 
or 
Page affected 
Description of change   
1.0 
New Protocol 
 
 
2.0 
Allow for visit 2 and 3 timing 
flexibility, no effect on data 
collection  
Section 3.1 and 
6.3 
(up to 3 days after study period is completed) 
2.1 
Typo  
Cover Page 
Correct date for Version History for Version 1.0 
August 16, 2017 to Version 1.0  August 7, 2017 
2.2 
Typo 
Header 
Corrected header and updated to Version 2.2 
and corrected date 
3.0 
Update for visit 2 and 3 timing 
flexibility, no effect on data 
collection 
Section 3.1 and 
6.3 
+/- 3 days, no fewer than 13 days and no more 
than 17 days 
4.0 
Non-insulin users use these 
32G pen needles for non-
insulin injections. 
 
Addition of 31G user with 
wash-in, to increase subject 
pool. 
Section 
1.0, 
2.0. 3.0, 3.2.3, 
4.0, 4.2, 4.3, 
5.3, 6.0, 8.2 
Added that non-insulin users only using pen 
needles for non-insulin injections could also be 
included in the study.  The users needed a 
minimum of one injection of non-insulin per 
day. 
Added 31G users with a wash in who were 
willing to switch to a 32G for the period of the 
study. 

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BD CONFIDENTIAL  
 
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Version # 
Rationale for Change 
Section 
or 
Page affected 
Description of change   
4.1 
Formatting corrections 
All 
Formatting of Heading 2 was corrected. 
5.0 
Broadened groups to allow 
wash-in 
of 
32G 
x 
4mm/5mm/6mm 
user 
to 
increase subject pool 
 
Inclusion/Exclusion Criteria 
Section 3.1 
 
 
Section 4.0 
 
Subjects using 32G under 6mm in length (such 
as BD Nano) could be washed-in to fill up other 
groups 
Decrease in I/E Criteria from 6 months to 3 
months for self- injecting with a pen injector 
and decrease from 3 months to 1 month for use 
with one of the competitor products 
 
 
 

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18.0 
APPENDICES 
The following appendices are attached: 
18.1 Non-comparative Questionnaire  
18.2 Comparative Questionnaire 
18.3 Diary 
18.4 Randomization Schedule 
18.5 Proficiency Questionaire 

Signature Page for DBC-17NUCLS07 Protocol 
Signature Page for DBC-17NUCLS07 Protocol - System Version No. 8.0
Approved
Shahista Kassam WW Assoc. Manager, Diabetes Care
Medical Affairs
Medical Affairs
21-Dec-2017 16:54:48 GMT+0000
Approved
Rianka Bhattacharya
Statistician
21-Dec-2017 17:26:15 GMT+0000
Approved
Laurence Hirsch VP Global Medical Affairs -Diabetes
Care, BD Medical
Medical Director
22-Dec-2017 02:42:12 GMT+0000
Approved
Brian Pflug Dir, Medical Affairs
Medical Director
22-Dec-2017 17:52:50 GMT+0000