PRECISION Study: A Prospective, Multi-center Evaluation of Precision, Compression and Performance of a Novel Implanted Continuous Glucose Sensor Using a Next Generation Transmitter and Algorithm
Phase: NA
Conditions: Diabetes Mellitus, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2
Sponsor: Senseonics, Inc.

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Protocol #:  CTP-0031   , Version 04   
 
Effective Date: 29 Sep. 2017 29 Sep 2017 
 
 
 
 
 
 
 
 
Title of Protocol: PRECISION Study: A Prospective, Multicenter Evaluation 
of Precision, Compression, Accuracy and Updated Algorithm of a Novel 
Continuous Implanted Glucose Sensor   
Protocol Number: CTP-0031 
Protocol Version: 04 
  Effective Date: 29 September 2017 
 
 
Senseonics, Incorporated 
20451 Seneca Meadows Parkway 
Germantown, MD 20876 
USA 
 
 
 
Confidential Information 
Property of Senseonics, Incorporated ® 
 
This Clinical Protocol contains confidential information for use by the investigators and their 
designated representatives participating in this clinical investigation. It must be held as 
confidential and maintained in a secure location.  It must not be copied or made available for 
review by any unauthorized person or firm. 
 
 

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GENERAL INFORMATION AND CONTACTS 
 
Sponsor 
Senseonics, Incorporated 
20451 Seneca Meadows Parkway 
Germantown, Maryland 20876-7005 
Lead Principal 
Investigator 
Mark Christiansen MD 
Diablo Clinical Research 
2255 Ygnacio Valley Road, Suite M  
Walnut Creek, CA 94598 
Study Sites 
Rainier Clinical Research Center 
723 SW 10th Street, Suite 100  
Renton, WA 98057 
Diablo Clinical Research 
2255 Ygnacio Valley Road, Suite M  
Walnut Creek, CA 94598 
AMCR Institute Inc. 
 
625 West Citracado Parkway Suite 112  
Escondido, California 92025 
Clinical Trials of Texas  
7940 Floyd Curl Dr. Suite 700 
San Antonio, Texas 78229 
CRO/Monitoring 
Regulatory & Clinical Research Institute, Inc. 
5353 Wayzata Blvd., Suite 505 
Minneapolis, Minnesota 55416 
Safety Contact 
E Lynne Kelley MD, FACS 
Chief Medical Officer 
Senseonics Incorporated 
Medical Monitor 
Grace A. Carlson, MD, MBA 
277 32nd Avenue 
San Francisco, CA 94121 
 
 
 
 

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PROTOCOL SIGNATURE PAGE (Sponsor) 
 
 
PRECISION Clinical Study Protocol (CTP-0031) 
 
 
 
 
                  Signed and Dated Electronically  
______________________________________  
 
     _________________________ 
Katherine Tweden, Vice President, Clinical Sciences  
 
 
 Date 
    
 
                   
 
  
 
 
 
 
 
 
  
09/28/2017 
__________________________________________                                ____________________________ 
David Y. He, Statistical Consultant 
 
 
 
 
                Date 
 
 
 

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PROTOCOL SIGNATURE PAGE 
 
 
Investigator’s statement 
 
I agree to conduct this clinical investigation in accordance with the design and specific 
provisions of this protocol and all applicable regulatory requirements. Modifications to the 
clinical investigation are acceptable only with a mutually agreed upon protocol amendment as 
approved by the sponsor, regulatory bodies and Institutional Review Board/ Ethics 
Committee. I agree to await Institutional Review Board/ Ethics Committee approval of the 
protocol, informed consent, and sponsor approval before initiating the study, and to obtain 
consent from subjects prior to their enrollment in the study. I agree to collect and record data 
as required by the protocol and case report forms, and to maintain study documents for the 
period of time required. 
 
 
Confidential 
 
This document contains confidential information belonging to Senseonics, Inc. Except as may 
be otherwise agreed to in writing, by accepting or reviewing these materials, I agree to hold 
such information in confidence and not to disclose it to others (except where required by 
applicable law), nor use it for unauthorized purposes. 
 
 
 
 
 
 
 
 
 
 
Investigator’s signature 
Date of signature 
 
 

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SYNOPSIS 
 
Title of Protocol 
PRECISION Study: A Prospective, Multicenter Evaluation of Precision, 
Compression, Accuracy and Updated Algorithm of a Novel Continuous 
Implanted Glucose Sensor   
Sponsor 
Senseonics, Inc. 
Investigational 
Device 
Senseonics Continuous Glucose Monitoring (CGM) System (the “System”) 
Reference 
Instrument 
Reference Glucose Analyzer (bedside, YSI 2300 STAT PLUS® Glucose 
and Lactate Analyzer, Yellow Springs Instruments, Yellow Springs, 
OH, USA). 
 
Calibration 
Standard 
FDA-cleared Blood Glucose Meter (Subject SMBG Meter) 
 
 
Study Purpose 
The purpose of this clinical investigation is to evaluate the precision and 
accuracy of the Senseonics Continuous Glucose Monitoring System 
(Senseonics CGM System) measurements when compared with reference 
standard measurements. Compression of the sensor site and use of a new 
algorithm will also be evaluated.  The investigation will also evaluate 
safety of the Senseonics CGM System usage. 
 
 
 
Target 
Indication for 
Use 
The Senseonics CGM System is a glucose monitoring device intended to 
continually measure interstitial fluid glucose levels in individuals with 
diabetes for the operating life of the sensor. The Senseonics CGM 
System is intended to be used: 
• 
To provide real-time glucose readings directly to the user. 
• 
To provide glucose trend information. 
• 
To provide alerts for the detection and prediction of episodes 
of low blood glucose (hypoglycemia) and high blood glucose 
(hyperglycemia). 
 
Study Design 
Summary 
This is a non-randomized, prospective, single-arm, multi-center study, 
enrolling   adult subjects with diabetes mellitus in the United States at 
up to 4 sites. The investigation will include both clinic visits and home 
use of the Senseonics CGM System. Subjects will have one or two 
Sensors inserted in the upper arms by trained Investigators.  The 
accuracy of the system will be evaluated during clinic visits, comparing 
Sensor glucose with laboratory reference values. For qualifying 
subjects, during the clinic visits, there are planned hyperglycemia and 
hypoglycemia challenges, as described in protocol Section 5.     All 
diabetes care decisions will be based on   plasma glucose values, rather 
than System CGM results. 
 

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Visit Schedule: 
• 
Visit 1 Screening Visit. Following informed consent process, 
screening evaluation will determine subject eligibility for 
enrollment. Visit lasting approximately 2 hours. Visit includes 
screening medical and diabetes history, examination and 
laboratory assessments. 
 
• 
Visit 2 Sensor Insertion Visit (Day 0, visit window: Visit 1 +0-30 
Days). Sensors will be inserted by Investigator in the upper arms. A 
minimum of 6 and a maximum of 9 subjects will receive one 
sensor. Remaining subjects will receive two sensors, one in each 
arm.  Subject receives training on study and devices. In addition for 
a group of subjects, 3 blood draws post-insertion will be done to 
measure dexamethasone levels. Visit lasting approximately 2-6 
hours. 
 
• 
Sensor Accuracy Visits. The following visits include Sensor accuracy 
assessment with reference laboratory glucose comparison, Sensor 
calibration with BG meter, and safety assessments including blood 
draws to measure dexamethasone levels. Protocol Section 4 
describes the procedure details, including hyperglycemia challenges 
and hypoglycemia challenge for eligible subjects. 
• Visit 3 (Day 1 ± 0 Day). Visit lasting approximately 19 hours.  
• Visit 4 (Day 7 ±1 Day). Visit lasting approximately 18 hours. 
• Visit 5(Day 14 ±1 Day). Visit lasting approximately 18 hours.  
• Visit 6 (Day 30 ±7 Days). Visit lasting approximately 14 hours. 
• Visit 7(Day 60 ±7 Days). Visit lasting approximately 14 hours. 
• Visit 8 (Day 90 -3/+7 Days). Visit lasting approximately 15 
hours.   
Following evaluation of Sensor accuracy, Sensors are removed 
at end of visit. 
 
• 
Visit 9 Follow-up Visit. Sensor Site Assessment is performed 
approximately 10 days after Sensor removals (- 3/ +7 day window) 
to assess Sensor sites. At this visit, if there is a concern by 
investigator about healing of sensor site, subject will return in 
approximately 10 days and followed until resolution. 
Home Use: Subjects will follow their usual diabetes care routine as per 
their medical team recommendations while wearing the System. All 
diabetes management decisions by the subject and health care team will 
be made based on standard of care with blood glucose monitoring, and 
not based on Senseonics CGM glucose values. Subjects will be advised to 
wear the Transmitter over the Sensor for data collection, except during 
transmitter charging, bathing or water activity. 
 

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Subjects will calibrate the CGM using the study-provided Subject SMBG 
Meter a minimum of two times per day according to Instructions for 
Use (Four times per day during Initialization Phase). Subject will use the 
same study-provided BG meter for monitoring their diabetes care, and 
this meter will be downloaded during the clinic visits. Subjects will be 
requested to check the BG meter glucose for all diabetes care decisions 
at a minimum 4-7 times per day. 
 
Clinic Visits: Blood samples, meter BG, and Sensor glucose values will 
be collected. Diabetes care decisions during the visit will be made 
based on blood glucose determinations, rather than Senseonics CGM 
System results.  
 
During sampling period  blood sample glucose measurements will be 
performed and collected for laboratory glucose reference analysis 
approximately every 15 minutes, and more frequently (approximately 
every 5 minutes) during periods of hypoglycemia and  hyperglycemia as 
described in the protocol. 
Safety Assessments and Management 
As described in Section 7.1, there will be trained staff and an emergency 
cart available at the site at all times. Safety guidelines will be utilized for 
subject care during periods of hyperglycemia (including monitoring 
blood ketones) and hypoglycemia. A physician or nurse practitioner will 
be available at all times during hypoglycemia and hyperglycemia 
challenges. 
 
The sensor insertion sites will be assessed at each clinic visit. A review 
and documentation of adverse events occurring in the clinic and 
during home use will be on-going. 
 
Laboratory tests will be monitored as per protocol for safety 
assessment. Additional details of the study design and safety 
assessments and management are described in the protocol.  Blood 
draws for Dexamethasone measurement will be made at Screening 
and on Visits 2-8. A subset of a minimum of 6 and a maximum of 9 
subjects will also have blood draws for dexamethasone measurement 
at days 3-6 of sensor use to identify possible blood draw time points 
during the first week of sensor wear for the remaining subjects.  

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Estimated 
Study Duration 
of Study and 
Subject 
Participation 
Enrollment Period: Approximately 2 months 
Individual Subject Participation: 
Approximately 4.5 months  
Duration of Study: Approximately 6 
months 
Study Sites 
Up to 4 investigative sites located in the United States. 
Subject 
Population 
The subject population consists of adult subjects with diabetes 
mellitus. Based on sample size calculations, approximately 44 adult 
subjects will be enrolled and approximately 36 will be inserted with 
the CGM Sensor in the investigation.  
 
 
Inclusion 
Criteria 
Male and Female Subjects meeting all of the following inclusion 
criteria will be included in this study: 
1. Adult subjects, age ≥18 years 
2. Clinically confirmed diagnosis of diabetes mellitus for ≥1 year 
3. Subject has signed an informed consent form and is willing to 
comply with protocol requirements 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Exclusion 
Criteria 
Subjects meeting any of the following exclusion criteria at the time of 
screening will be excluded from this study: 
1. History of severe hypoglycemia in the previous 6 months. Severe 
hypoglycemia is defined as hypoglycemia resulting in loss of 
consciousness or seizure 
2. History of diabetic ketoacidosis requiring emergency room visit or 
hospitalization in the previous 6 months 
3. Female subjects of childbearing capacity (defined as not surgically 
sterile or not menopausal for ≥ 1 year) who are lactating or 
pregnant, intending to become pregnant, or not practicing birth 
control during the course of the study. 
4. A condition preventing or complicating the placement, operation, 
or removal of the Sensor or wearing of transmitter, including 
upper extremity deformities or skin condition.  
5. Symptomatic coronary artery disease; unstable angina; myocardial 
infarction, transient ischemic attack or stroke in the past 6 months; 
uncontrolled hypertension (systolic>160 mm Hg or diastolic >100 
mm Hg at time of screening); current congestive heart failure; 
history of cardiac arrhythmia (benign PACs and PVCs allowed). 
Subjects with asymptomatic coronary artery disease (e,g, CABG, 
stent placement or angioplasty) may participate if negative stress 
test within 1 year prior to screening and written clearance from 
Cardiologist documented.  
6. Hematocrit <30% or >55%  
7. History of hepatitis B, hepatitis C, or HIV 
8. Current treatment for a seizure disorder unless written clearance 
by neurologist to participate in study 
9. History of adrenal insufficiency 

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10. Currently receiving (or likely to need during the study period): 
immunosuppressant therapy; chemotherapy; 
anticoagulant/antithrombotic therapy (excluding aspirin); 
glucocorticoids (excluding ophthalmic or nasal). This exclusion 
does include the use of inhaled glucocorticoids and the use of 
topical glucocorticoids (over sensor site only); antibiotic for 
chronic infection (e.g. osteomyelitis, endocarditis) 
11. A condition requiring or likely to require magnetic resonance imaging 
(MRI) 
12. Known topical or local anesthetic allergy 
13. Known allergy to glucocorticoids 
14. Any condition that in the investigator’s opinion would make the 
subject unable to complete the study or would make it not in the 
subject’s best interest to participate in the study. Conditions 
include but are not limited to psychiatric conditions, known current 
or recent alcohol abuse or drug abuse by subject history, a 
condition that may increase the risk of induced hypoglycemia or 
risk related to repeated blood testing. Investigator will supply 
rationale for exclusion 
15. Participation in another clinical investigation (drug or 
device)  within 2 weeks prior to screening or intent to 
participate during the study period 
16. The presence of any other active implanted device (as defined further 
in protocol) 
17. The presence of any other CGM sensor or transmitter located in 
upper arm (other location is acceptable) 
 
 
 
Investigation 
Objectives 
Effectiveness Objective: 
To determine accuracy of the Senseonics CGM System measurements 
through approximately 90 days post-insertion. An interim analysis will 
be conducted on all subjects after completion of Visit 6 (day 30 
accuracy visit). 
 
Safety Objective: 
To demonstrate safety of the Senseonics CGM System  through 90 days 
post-insertion or sensor removal and follow-up by measuring the 
incidence of device-related and insertion/removal procedure-related 
serious adverse events during the investigation. 
Endpoints 
Effectiveness Endpoint: 
The effectiveness endpoint will be mean absolute relative difference 
(MARD) for paired Sensor and reference measurements through 90 days 
post-insertion for reference glucose values from 40-400 mg/dL. This 
endpoint will be evaluated descriptively.  Neither inferential analysis nor 
hypothesis testing will be performed An interim analysis will be conducted 
on all subjects after completion of Visit 6 (day 30 accuracy visit). 
 

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Safety Endpoint: 
Incidence of device-related or sensor insertion/removal procedure-related 
serious adverse events through 90 days post-insertion or sensor removal 
and follow-up. 
 
 
 
Other Safety 
Endpoints 
1. Incidence of all device-related or sensor insertion/removal procedure-
related adverse events in the clinic and during home use. 
2. Incidence of all adverse events in the clinic and during home use. 
3. Incidence of hospitalizations due to hypoglycemia, 
hyperglycemia or ketoacidosis occurring during home use. 
4. Incidence of reported hypoglycemic and hyperglycemic events 
occurring during home use. 
 
 
 

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ABBREVIATIONS 
 
AE Adverse Event 
BG Blood Glucose 
BG Meter Blood Glucose Meter (also known as SMBG Meter) 
β-HOB β-hydroxybutyrate or “ketones,” also abbreviated B-HOB 
BMI Body Mass Index 
CD Compact disc 
CFR Code of Federal Regulations 
CGM Continuous Glucose Monitoring  
CRF Case Report Form 
CRO Contract Research Organization  
DCF Data Clarification Form 
DKA Diabetic Ketoacidosis 
eCRF Electronic Case Report Form 
EKG Electrocardiogram (also commonly abbreviated as ECG)  
FDA Food and Drug Administration 
GCP Good Clinical Practice 
HbA1c Hemoglobin A1c or A1C  
HCT Hematocrit 
HIV Human Immunodeficiency Virus 
HHD Hand Held Device 
ICH International Conference on Harmonization 
IRB Institutional Review Board 
ISO International Organization for Standardization  
MARD Mean absolute relative difference 
MAD Mean absolute difference 
MDI Multiple Daily Injections 
MMA Mobile Medical Application   
MRD Mean relative difference 
PARD Percent absolute relative difference 
PI Principal Investigator 
POC Point of Care 
SAE Serious Adverse Event 
SMBG Self-Monitoring Blood Glucose 
SQ Subcutaneous 
UADE Unanticipated Adverse Device Effect  
USB Universal Serial Bus 
YSI Yellow Springs International (Blood glucose analyzer) 
 
 

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1 
INTRODUCTION, IDENTIFICATION OF THE INVESTIGATIONAL DEVICE, AND RATIONALE ........... 15 
1.1 
Names, Intended Use, and Description of Study Device ..................................................... 15 
1.2 
Summary of Pre-clinical and Clinical Experience ............................................................... 18 
2 
STUDY OBJECTIVES ................................................................................................................... 19 
2.1 
Effectiveness ..................................................................................................................... 19 
2.2 
Safety ................................................................................................................................ 19 
3 
STUDY DESCRIPTION ................................................................................................................. 19 
3.1 
Study Population ............................................................................................................... 19 
3.2 
Inclusion and Exclusion Criteria .......................................................................................... 19 
3.3 
Study Design ...................................................................................................................... 21 
4 
STUDY METHODS, PROCEDURES AND CLINIC VISITS ................................................................. 23 
4.1 
Visit 1 – Screening/Enrollment .......................................................................................... 25 
4.2 
Visit 2 – Sensor Insertion/Training .................................................................................... 26 
4.3 
Subset of subjects for dexamethasone analysis ................................................................ 29 
4.4 
Sensor Accuracy (Sampling) Visit 3 – Day 1 (± 0 Days) ....................................................... 29 
4.5 
Sensor Accuracy (Sampling) Overnight Visits .................................................................... 35 
4.6 
Sensor Accuracy (Sampling) Daytime Visits ....................................................................... 39 
4.7 
Visit 8, Day 90 Sensor Removal ......................................................................................... 44 
4.8 
Visit 9 –Follow-up Visit (10 days following sensor removal. Window: sensor removal date 
+7 to 17 Days) ................................................................................................................... 45 
5 
GENERAL CONSIDERATIONS FOR STUDY VISITS ........................................................................ 45 
5.1 
Definition of Enrollment .................................................................................................... 45 
5.2 
Medications and medical supplies .................................................................................... 45 
5.3 
Device setup ...................................................................................................................... 46 
5.4 
Measurement Devices – Maintenance/Control Testing .................................................... 46 
5.5 
Senseonics Continuous Glucose Monitoring (CGM) System Calibration ........................... 47 
5.6 
Use of Study Devices for Diabetes Treatment ................................................................... 47 
5.7 
Fingersticks ........................................................................................................................ 47 
5.8 
Ketones ............................................................................................................................. 48 

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5.9 
IV/Blood Draw Guidelines ................................................................................................. 48 
5.10 Sensor Replacement .......................................................................................................... 49 
5.11 Sponsor Presence at Visits................................................................................................. 50 
5.12 Glucose challenges ............................................................................................................ 50 
5.13 Example Meal Choices ....................................................................................................... 53 
5.14 Discharge instructions – Sensor accuracy visits ................................................................. 55 
5.15 Photograph/Videography .................................................................................................. 56 
6 
CLINICAL LABORATORY EVALUATIONS AND ESTIMATED BLOOD VOLUMES .............................. 56 
7 
SUBJECT SAFETY, STOPPING RULES, AND STUDY EXIT ............................................................... 57 
7.1 
Diabetes and Safety Considerations during Clinic Visits .................................................... 57 
7.2 
Subject Stopping Rules ...................................................................................................... 62 
7.3 
Study Stopping Rules ......................................................................................................... 64 
7.4 
Termination of Investigator or Investigational Site ............................................................ 65 
8 
RISK AND BENEFIT ANALYSIS ..................................................................................................... 65 
8.1 
Potential Benefits .............................................................................................................. 65 
8.2 
Potential Risks ................................................................................................................... 66 
8.3 
Efforts to Minimize Risk ..................................................................................................... 71 
8.4 
Risk to Benefit Ratio ........................................................................................................... 71 
9 
ADVERSE EVENTS ...................................................................................................................... 72 
9.1 
Adverse Event Definitions .................................................................................................. 72 
9.2 
Monitoring of Adverse Events ............................................................................................ 74 
9.3 
Adverse Event Reporting ................................................................................................... 74 
9.4 
Device Deficiencies ............................................................................................................ 75 
10 SOURCE DOCUMENTATION, CASE REPORT FORMS AND DATA MANAGEMENT ........................ 75 
10.1 Source Documents and Case Report Forms ...................................................................... 75 
10.2 Glucose Measurement Data Flow Process ......................................................................... 76 
11 Statistical Methods ................................................................................................................... 77 
11.1 Statistical Analysis Overview ............................................................................................. 77 
11.2 Safety Endpoints ............................................................................................................... 80 

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11.3 Effectiveness Endpoints .................................................................................................... 81 
12 DEVICE ACCOUNTABILITY .......................................................................................................... 83 
13 ETHICAL AND REGULATORY CONSIDERATIONS ......................................................................... 83 
13.1 Statement of Compliance and Good Clinical Practice ........................................................ 83 
13.2 Informed Consent and Investigational Review Board ........................................................ 84 
13.3 Payment for Participants ................................................................................................... 85 
13.4 Amendments to the Protocol ............................................................................................ 85 
13.5 Sponsor Responsibilities .................................................................................................... 85 
13.6 Investigator Responsibilities and Delegation of Study-Specific Tasks ................................. 85 
13.7 Training ............................................................................................................................. 86 
13.8 Protocol Compliance .......................................................................................................... 86 
13.9 Protocol Deviation ............................................................................................................. 87 
13.10 Document Storage and Retention ..................................................................................... 87 
13.11 Confidentiality of Data ....................................................................................................... 87 
13.12 Clinical Study Monitoring ................................................................................................... 88 
13.13 Medical Monitor ................................................................................................................ 88 
13.14 Auditing ............................................................................................................................. 89 
13.15 Insurance and Indemnity ................................................................................................... 89 
14 FINAL REPORT ........................................................................................................................... 89 
15 PUBLICATION POLICY ................................................................................................................ 89 
16 REFERENCES ............................................................................................................................. 91 
17 APPENDIX 1 EXAMPLE FIGURES AND TABLES OF STATISTICAL ANALYSIS RESULTS ................... 92 
 
 

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1 
INTRODUCTION, IDENTIFICATION OF THE INVESTIGATIONAL DEVICE, AND RATIONALE 
 
In spite of recent improvement in therapies, diabetes mellitus continues to be a difficult 
medical condition to treat. The challenge remains to achieve desired glycemic control and to 
prevent both the short-term consequences (severe hypoglycemia and DKA) and long-term 
complications (retinopathy, neuropathy, nephropathy and cardiovascular problems).  The 
monitoring of blood glucose by the patient with diabetes is one of the key tools of diabetes 
self-care. The current standard glucose monitoring regimen for patients with diabetes involves 
using a small portable meter to obtain a capillary fingertip glucose measurement multiple 
times a day. According to the International Society of Pediatric and Adolescent Diabetes 
(ISPAD), “successful application of intensified diabetes management with multiple injection 
therapy or insulin infusion therapy requires frequent self-monitoring of blood glucose (four to 
six times a day) and regular, frequent review of the results to identify patterns requiring 
adjustment to the diabetes treatment plan.”1    Despite this diagnostic procedure and 
therapeutic interventions, due to the nature of diabetes glucose values may fluctuate widely 
throughout the day. In addition, as the BG meter value shows only a point in time glucose 
level, even patients who monitor frequently, may miss significant hypoglycemic and 
hyperglycemic excursions. Continuous glucose monitoring (CGM), which measures interstitial 
glucose levels, has been developed recently and has been shown to be associated with 
improved glycemic control in adults with type 1 diabetes. Current commercially available CGM 
devices require the repeated, frequent insertion of a sensor by the patient. 
 
Senseonics, Inc. a medical device manufacturer headquartered in Germantown, Maryland, 
USA, is developing a new CGM System   intended for measuring interstitial fluid glucose levels 
in adults with diabetes mellitus.  The Senseonics CGM System measures interstitial fluid 
glucose levels continuously and is implanted under the skin by a trained clinician. Unlike 
commercially available transcutaneous continuous glucose monitoring devices with short 
operating lives (up to 7 days), the Senseonics Sensor is intended to be inserted 
subcutaneously with no sensor part protruding from the skin, and the operating life is 
intended to be up to 90 days or until the end of life indicator is reached. 
This clinical trial is being carried out to assess the safety and efficacy of the Senseonics CGM 
System. It is intended that the results of this study will support the targeted indication as 
described in Section 1.1 below, providing quantification of accuracy and demonstrate safety 
in clinic and home use settings over the operating life of the Sensor. 
 
1.1 
Names, Intended Use, and Description of Study Device 
The study investigational Device is the Senseonics CGM System (“System”). 
 

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The Senseonics Continuous Glucose Monitoring System is a glucose monitoring device 
intended to continually measure interstitial fluid glucose levels in individuals with diabetes 
for the operating life of the sensor. The Senseonics Continuous Glucose Monitoring System 
is intended to be used: 
• To provide real-time glucose readings directly to the user 
• To provide glucose trend information 
• To provide alerts for the detection and prediction of episodes of low 
blood glucose (hypoglycemia) and high blood glucose (hyperglycemia). 
 
           The Senseonics CGM System consists of: 
 
1. Glucose Sensor, (approximately 3.5 mm [0.138”] diameter x 18.3 mm [0.720”] length) 
which has a ring that elutes the steroid dexamethasone 
 
2. Battery-powered external Transmitter (“Transmitter”, Gen1/Gen2) 
3. Mobile Medical Application (MMA) for display of glucose information that runs on a 
Handheld Device (HHD). 
 
 
         
     Accessories to the system include: 
1. Blunt dissector for creating a pocket under the skin 
 
2. Insertion tool used to place the Sensor into the pocket. 
 
3. Transmitter accessories (power supply, adhesive patches)  
 
Senseonics’ continuous glucose monitoring system has been branded for commercial use as 
the Eversense Continuous Glucose Monitoring (CGM) System. System components may be 
branded as Senseonics or as Eversense. The use of the system in this clinical study is outside 
the current commercial indications for use. 
 
Gen 2 
Transmitter 
Gen 1 
Transmitter 

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1.1.1 Description 
The Senseonics CGM Sensor uses a selective, fully reversible binding between glucose and a 
unique fluorescent indicator macromolecule that is grafted on the surface of the Sensor. 
The fundamental recognition reaction is a reversible condensation of the cis-diol groups of 
glucose with the bis-boronate moiety of an indicator. Glucose binding by the indicator 
macromolecule results in an increase in fluorescence intensity. Glucose signal transduction 
is accomplished by measuring the fluorescence intensity modulation using the Sensor’s 
optical system. 
The Senseonics System Transmitter powers the Sensor and receives signals from the 
Sensor across the skin.  The Sensor does not contain a battery or other stored power 
source; instead it is powered discretely, as needed, by a simple inductive magnetic link 
between the Transmitter and Sensor. Signals carrying glucose concentration data are 
superimposed upon the magnetic power link between the two components. This results 
in “passive” telemetry, rather than an “active” radio frequency (RF) transmission, 
between the Sensor and Transmitter. Between readings, the Sensor remains electrically 
dormant and fully powered down. At each query (automatically set for approximately 
every five minutes, with a duration of approximately 100 milliseconds), the Transmitter 
sends power (via magnetic link) to activate the sensor, and then uses this same magnetic 
link to capture the reading. Finally, the Transmitter calculates and stores the measured 
glucose value for transmission to the Mobile Medical Application. 
Components of the Senseonics CGM System are traced by serial number and/or lot 
number. The Sensor, Sensor holder, insertion tool, and blunt dissector are provided sterile. 
Sterilized components also have an expiration date. The device is labeled in compliance 
with regulatory language requirements identifying it as investigational. The Instructions for 
Use are provided with each shipment. 
Insertion of the Sensor is a minimally invasive procedure and clinical investigators 
representing the intended use population (Endocrinologists, Internists, General and Family 
Practitioners) will be appropriately trained in the procedure prior to insertion or removal 
of the Sensor. Training and qualifications of investigators will be documented. 
 
Transmitters will be provided for single-subject use in this clinical trial. 
1.1.2 Calibration 
The primary Senseonics CGM System will be calibrated by the Subjects according to the 
Eversense CGM User Guide, using the study-provided, commercially available BG Meter 
(Subject SMBG Meter), according to the SMBG meter manufacturer instructions. The 

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calibration process automatically moves through three phases: Warm Up, Initialization, and 
Daily Calibration: 
 
• Warm Up is the first 24 hours after Sensor insertion. During this period, Glucose 
information is not calculated. No calibration is performed. 
• Initialization can be performed a minimum of 24 hours after Sensor insertion. Following 
the Warm Up phase, the entering of four successful calibration BG readings within 24 
hours is required for successful completion of Initialization. Glucose information will 
begin to be calculated   after the second calibration is entered successfully. 
• Daily Calibration requires 2 successful calibrations per day, a minimum of 10 and 
maximum of 14 hours apart. 
 
If the Subject fails to wear the Transmitter for more than 24 hours, or is unable to enter a 
successful calibration, then glucose information will not be calculated and the Subject will 
re-enter the Initialization phase. 
 
The secondary Senseonics CGM System will not require calibration and will have the ability 
to collect and log data only, and it will not calculate or store glucose information.  
 
1.2 
Summary of Pre-clinical and Clinical Experience 
Bench testing and animal testing have been conducted on the Senseonics CGM System to 
characterize performance, evaluate biocompatibility and demonstrate proof of principle in 
primates. Results of these tests are presented in the Report of Prior Investigations. 
Clinical experience has included healthy volunteers and people with type 1 and 2 diabetes. 
As of February 2017, the Senseonics CGM System has been tested in two feasibility studies 
in the US. Other initiated Competent Authority/FDA and EC/IRB-approved feasibility studies 
include studies in the UK (Manchester), India (Mumbai, Pune), Romania (Bucharest Study I, II 
and III), Belgium (Brussels), South Africa (Cape Town), US (Set-Point Study), Canada and 
Sweden (HOUSE). Two pivotal studies, PRECISE Study (in the EU) and PRECISE II Study (in the 
US) were also conducted. As of February 2017, a total of 556 subjects have been inserted 
with 983 sensors with days in-vivo totaling 102,665 days.  
These studies demonstrated that the Senseonics CGM System provided reliable interstitial 
fluid glucose readings for periods of up to approximately 180 days when compared to 
laboratory blood glucose analyzer measurements, with no noted safety issues. Detailed 
presentation of methods and results for each investigation are presented in the Report of 
Prior Investigations. 
 
 

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2 
STUDY OBJECTIVES 
 
2.1 
Effectiveness 
The effectiveness objective is to determine the accuracy of the Senseonics CGM System 
through 90 days post-insertion for reference glucose values from 40-400 mg/dL. The 
exploratory objectives are to determine other relevant Senseonics CGM System 
performance measures during the period of Sensor use and are detailed further in Section 
11.3, along with plans and analysis details on the effectiveness endpoint. An interim 
analysis will be performed and data submission will be made based on the sensor 
performance data accrued through the day 30 visit (Visit 6). 
2.2 
Safety 
The safety objective is to demonstrate safety of the Senseonics CGM System through 90 days 
post-insertion by measuring the incidence of device-related or sensor insertion/removal 
procedure-related serious adverse events (SAEs) during the investigation. The other safety 
objectives are to evaluate the incidence of all procedure-related or device-related adverse 
events (AEs) in clinic and home use, and to evaluate the incidence of all adverse events, 
regardless of relatedness, in clinic and home use.  The safety endpoints and their respective 
analysis are detailed further in Section 11.2. 
 
 
3 
STUDY DESCRIPTION 
 
3.1 
Study Population 
The study population includes adults with diabetes mellitus. 
 
3.2 
Inclusion and Exclusion Criteria 
3.2.1 Inclusion Criteria 
Male and Female Subjects meeting all of the following inclusion criteria will be included in 
this study: 
1. 
Adult subjects, age ≥18 years 
2. 
Clinically confirmed diagnosis of diabetes mellitus for ≥1 year.   
3. 
Subject has signed an informed consent form and is willing to comply with protocol 
requirements 
3.2.2 Exclusion Criteria 
Subjects meeting any of the following exclusion criteria at the time of screening will be 
excluded from this study: 
1. History of severe hypoglycemia in the previous 6 months. Severe hypoglycemia is 
defined as hypoglycemia resulting in loss of consciousness or seizure 

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2. History of diabetic ketoacidosis requiring emergency room visit or hospitalization in 
the previous 6 months 
3. Female subjects of childbearing capacity (defined as not surgically sterile or not 
menopausal for ≥ 1 year) who are lactating or pregnant, intending to become 
pregnant, or not practicing birth control during the course of the study 
4. A condition preventing or complicating the placement, operation or removal of the 
Sensor or wearing of transmitter, including upper extremity deformities or skin 
condition 
5. Symptomatic coronary artery disease; unstable angina; myocardial infarction, transient 
ischemic attack or stroke within 6 months; uncontrolled hypertension (systolic>160 mm 
HG or diastolic >100 mm Hg at time of screening); current congestive heart failure; 
history of cardiac arrhythmia (benign PACs and PVCs allowed). Subjects with 
asymptomatic coronary artery disease (e.g. CABG, stent placement or angioplasty) may 
participate if negative stress test within 1 year prior to screening and written clearance 
from Cardiologist documented. 
6. Hematocrit <30% or >55% 
7. History of hepatitis B, hepatitis C, or HIV 
8. Current treatment for a seizure disorder unless written clearance by neurologist to 
participate in study 
9. History of adrenal insufficiency 
10. Currently receiving (or likely to need during the study period): immunosuppressant 
therapy; chemotherapy; anticoagulant/antithrombotic therapy (excluding aspirin); 
glucocorticoids (excluding ophthalmic or nasal). This exclusion does include the use of 
inhaled glucocorticoids and the use of topical glucocorticoids (over sensor site only); 
antibiotics for chronic infection (e.g. osteomyelitis, endocarditis) 
11. A condition requiring or likely to require magnetic resonance imaging (MRI) 
12. Known topical or local anesthetic allergy 
13. Known allergy to glucocorticoids 
14. Any condition that in the investigator’s opinion would make the subject unable to 
complete the study or would make it not in the subject’s best interest to participate 
in the study. Conditions include, but are not limited to, psychiatric conditions, known 
current or recent alcohol abuse or drug abuse by subject history, a condition that may 
increase the risk of induced hypoglycemia or risk related to repeated blood testing. 
Investigator will supply rationale for exclusion 
15. Participation in another clinical investigation (drug or device) within 2 weeks prior 
to screening or intent to participate during the study period 
16. The presence of any other active implanted device* 

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17. The presence of any other CGM sensor or transmitter located in upper arm (other 
location is acceptable) 
 
* An example of an active implanted device includes, but is not limited to an implantable 
defibrillator. Passive implantable devices are allowed. An example of a passive implantable 
device includes, but is not limited to, a cardiac stent.   
 
3.3 
Study Design 
3.3.1 Overview 
This is a non-randomized, prospective, single-arm, multi-center study, whereby 
approximately 44 subjects will be enrolled and 36 subjects will be inserted in the United 
States at up to 4 sites. The investigation will include both clinic visits and home use of the 
Senseonics CGM System. The subjects will have one or two Sensors inserted by trained 
Investigators. The Sensors will be inserted in the upper arms of the subjects. The accuracy 
of the Senseonics CGM System will be evaluated during clinic visits comparing Sensor 
glucose values and plasma glucose values measured on a bedside glucose analyzer. For 
qualifying subjects, during the clinic visits, there will be planned hyperglycemia and 
hypoglycemia challenges, as described in Section 5.12. Effects of compression/sensor dropout 
will be evaluated during the designated overnight periods. 
 
In this study, including the clinic and home settings, all diabetes care decisions will be based 
on SMBG blood glucose values and clinical standard of care, rather than Senseonics CGM 
System results. 
This study will not be randomized. Subjects will be selected consecutively (i.e., selecting 
every subject in the order they present at the site) among those who meet the 
inclusion/exclusion criteria. 
 
The Subject visit schedule includes 9 visits over a period of approximately 4.5 months 
(inclusive of visit windows from screening visit through follow-up visit). 
 
A subset of a minimum of 6 and a maximum of 9 subjects will have blood samples drawn 
daily for the first 7 days of sensor wear for additional dexamethasone screening and to 
determine blood draw time points during the first week of sensor wear for the remaining 
subjects. These subjects will only have one sensor inserted in the left arm, which will be 
linked to the Gen 1 transmitter. Remaining subjects will have 2 sensors inserted, one in each 
arm, with the left sensor linked to a Gen 1 transmitter, and the right sensor linked to the Gen 
2 transmitter. These subjects may be required to make additional visits for dexamethasone 
screening between visits 3 and 4. 
 
The study is anticipated to take approximately 6 months, including the enrollment period.  

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3.3.2 Justification for Clinical Investigation Design 
The design of the clinical investigation was developed following a review of current 
published clinical studies evaluating the accuracy of continuous glucose monitors.2, 3, 4    In 
addition, the recommendations of the following standards and guidelines were considered 
in the clinical investigation design: 
 
• 
CLSI. Performance Metrics for Continuous Interstitial Glucose Monitoring: Approved 
Guideline. CLSI Document POCT05-A. Wayne, PA. Clinical and Laboratory Standards 
Institute. 2008.5 
• 
ISO. In-vitro Diagnostic Test Systems-Requirements for Blood Glucose Monitoring 
Systems for 
Self-Testing in Managing Diabetes Mellitus. ISO 15197. Geneva. 
International Organization for Standardization. 2013.6 
• 
FDA. Content of Premarket Submissions for Management of Cybersecurity in Medical 
Devices. Guidance. 2014.7 
• 
FDA. The Content of Investigational Device Exemption (IDE) and Premarket 
Approval (PMA) Applications for Artificial Pancreas Device Systems. Draft 
Guidance. 2011.8 
• 
FDA. Design Considerations for Pivotal Clinical Investigations for Medical Devices. Guidance 
2013.9 
 
The operational components of the investigation are consistent with: 
• 
US Code of Federal Regulations  (21 CFR Part 812) 
• 
ICH GCP E6 
 
Potential for bias during this investigation has been minimized by design of a well-controlled 
study, expected conduct under the terms of an approved study protocol, use of specific 
inclusion and exclusion criteria, careful definitions for study procedures and outcomes and 
prospectively defined methods of data analysis,  and careful selection of investigators and 
investigative sites. 
3.3.3 Overview of Visit Schedule: 
• Visit 1 Screening Visit. Following the informed consent process, the screening 
evaluation will determine subject eligibility for sensor insertion. This visit will last 
approximately 2 hours. Screening will include medical and diabetes history, physical 
examination and laboratory assessments including EKG.   
• Visit 2 Sensor Insertion Visit (Day 0, +0 to 30 Days after Visit 1).  Sensors are inserted 
by Investigator in the upper arms.   Subject training on study and devices. Visit lasting 
approximately 2 to 3 hours. Designated subjects for dexamethasone testing have only 
1 sensor inserted, and will be required to stay up to 6 hours. Depending on the results 
from this subset, all following subjects may be required to stay up to 6 hours for this 
visit. 

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• Sensor Accuracy Visits. The following visits include Sensor accuracy assessment 
with bedside reference comparison, Sensor calibration with Subject SMBG Meter, 
and safety assessments.   Procedure details are described in Section 4 of the 
protocol. 
• Visit 3 (Day 1 ± 0 Day). Visit lasting approximately 19 hours.  
• Visit 4 (Day 7 ±1 Days). Visit lasting approximately 18 hours. 
• Visit 5 (Day 14 ±1 Days). Visit lasting approximately 18 hours.  
• Visit 6 (Day 30 ±7 Days). Visit lasting approximately 14 hours 
• Visit 7 (Day 60 ±7 Days). Visit lasting approximately 14 hours 
• Visit 8 (Day 90 -3/+7 Days). Visit lasting approximately 15 hours.   
Following evaluation of Sensor accuracy, the Sensors are removed at the end of this 
visit. (Note: Sensor removals may also be performed at an unscheduled visit and will 
not be considered a protocol deviation) 
• 
 Visit 9: Follow Up Visit (10 days after Sensor removal, -3/ +7 day window). Sensor 
insertion/removal sites are assessed for healing. At this visit, if there is a concern by 
investigator about healing of sensor sites, the subject will return in approximately 10 
days and followed until resolution.   Visit length will be approximately 30 minutes. 
 
4 
STUDY METHODS, PROCEDURES AND CLINIC VISITS 
 
Each visit is described in detail in this section.  
Visit Number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
Visit Type 
Screening 
Sensor 
Insertion 
and 
Training 
Accuracy 
Visit 
Accuracy 
Visit 
Accuracy 
Visit 
Accuracy 
Visit 
Accuracy 
Visit 
Accuracy 
Visit and 
Sensor 
Removal 
Follow-up 
Sensor Site 
Assessment 
Study Day and 
Window 
 
Day 0 
 
(+0 to 30 
Days 
after 
Visit 1) 
Day 1 
Day 7 
Day 14 
Day 30 
Day 60 
Day 90 
10 Days 
Following 
Sensor 
Removal 
 
(±0 Day) 
(± 1 Days) 
(±1 
Days) 
(±7 Days) 
(±7 Days) 
(-3/+7 
days) 
(-3/+7 days)  
Anticipated Length 
of Visit 
2 
Hours 
2 to 6 
Hours 
19 
Hours 
18 
Hours 
18 
Hours 
14 hours 
14 
hours 
15 
hours 
30 
Minutes 
Informed Consent 
Process 
X 
 
  
  
  
  
  
  
  
Screening history, 
exam, labs to assess 
Inclusion/Exclusion 
X 
 
  
  
  
  
  
  
  
Sensor Insertion 
 
X 
  
  
  
  
  
  
  

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Visit Number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
Device Training 
 
X 
 
 
 
 
 
 
 
Urine pregnancy 
X 
X 
X 
X 
X 
X 
X 
X 
 
IV Catheter 
 
 
X 
X 
X 
X 
X 
X 
 
Approximate 
length of time to 
collect blood 
Samples 
  
  
16 
Hours 
16 
Hours 
16 
Hours 
12.5 
Hours 
12.5 
Hours 
12.5 
Hours 
  
Dexamethasone 
blood draw (4.0 
mL)2 
X 
X 
X3 
X3 
X3 
X 
X 
X 
 
HCT 
X 
 
X 
X 
X 
X 
X 
X 
 
A1C (2.0 mL) 
X 
 
 
 
 
X 
X 
X 
 
Fingerstick blood 
glucose and 
ketones per 
protocol 
 
 
X 
X 
X 
X 
X 
X 
 
Download 
Transmitter and BG 
Meters 
 
 
X 
X 
X 
X 
X 
X 
 
Assess changes in 
medications and 
Adverse Events 
 
X 
X 
X 
X 
X 
X 
X 
X 
Assess Sensor site 
  
 
X 
X 
X 
X 
X 
X 
X 
Hypoglycemia and 
Hyperglycemia 
Challenge 
  
 
X 
X 
X 
X1 
X1 
X1 
 
Sleep Assessment 
 
 
 
X 
X 
 
 
 
 
Questionnaire 
 
 
 
 
 
 
 
X4 
 
Sensor Removal 
  
 
 
 
 
 
 
X 
 
Approximate 
Samples for 
glucose analysis 
  
  
89 
89 
89 
59 
59 
59 
  
(13 hrs 
@4 
(13 hrs 
@4 
(13 hrs 
@4 
(11.5 hrs 
@4 
(11.5 hrs 
@4 
(11.5 hrs 
@4 
per, 3 hrs 
per), 3 hrs 
per), 3 
hrs 
per), 1 hr 
per), 1 hr 
per), 1 hr 
@ 12 per) 
@ 12 per 
@ 12 per 
@ 12 per 
@ 12 per 
@ 12 per 
Maximum 
Estimated Blood 
Draw Volume 
6 
12 
97 
97 
97 
65 
65 
65 
Total=504 
1 Only hypoglycemia challenge or hyperglycemia challenge, depending on glucose level 
2 Designated subjects will have 3 samples drawn at visit 2. A subset of subjects will have daily blood samples drawn for the first 7 days of sensor wear 

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for dexamethasone assessment. Remaining subjects may have an additional blood sample drawn during the first 7 days TBD based on the results from 
the subset. 
3 Subjects will have 2 blood samples drawn for dexamethasone assessment, one at the beginning of the visit, and one at the end. 
4 Subjects will be asked to complete a questionnaire at the end of sensor wear period.  
 
 
 
 
 Visit Details 
 
4.1 
Visit 1 – Screening/Enrollment 
Subjects will be enrolled into the study following informed consent. Screening evaluation will 
determine subject eligibility for sensor insertion. No study-specific procedures may be 
performed prior to informed consent signature. The Screening Visit is anticipated to last 
approximately 2 hours. The visit will occur within 30 days before the Sensor Insertion Visit 
(V2).  
The Screening Visit includes performing/collecting the following information:  
• Demographics- including age, gender at birth, race/ethnicity, dominant hand, and BMI.  
• Diabetes History- including type of diabetes, date of diagnosis or length of diabetes, 
history of DKA and severe hypoglycemia, current treatment (type of insulin and type of 
insulin delivery (injections or insulin pump),  insulin doses, and when applicable: basal 
rates, correction factors, glucose targets, insulin duration, insulin to carbohydrate ratios, 
sliding scales). 
• Current and Past Medical History- including concomitant medications. 
• Physical examination and vital signs- including height, weight, blood pressure, pulse, 
temperature, assessment of potential sensor insertion sites, assessment of venous access 
for repeated blood draws. 
• EKG- an EKG will be performed with the results kept in the subject records.   
• Laboratory  
Blood samples (approximately 6 ml total) will be drawn for the following laboratory tests. 
All samples will be collected and processed as described in the operations manual: 
o Hemoglobin A1C 
o Dexamethasone 

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4.1.1 Point of care testing 
• 
Urine pregnancy test- for females of childbearing capacity (defined as not surgically sterile 
or not menopausal for ≥ 1 year) 
• 
Hematocrit (using local lab or point of care testing device) 
 
4.2 
Visit 2 – Sensor Insertion/Training 
4.2.1 Subject Admission 
The subject will arrive at the clinic during the day, at an appropriate time to allow for sensor 
insertion to occur a minimum of 24 hours before the planned day 1 (Visit 3) study activities, 
and the following tests will be performed to confirm eligibility: 
• Female subjects of childbearing capacity will undergo a urine pregnancy test. If positive, 
the subject will discontinue study participation. Subject withdrawal will be documented. 
• The study team will confirm the absence of a febrile or vomiting illness within 24 hours of 
the admission. 
• If all admission criteria are not met, the subject will be rescheduled. If all of the 
admission readiness conditions are met, the subject will be admitted to the Clinical 
Research Unit.  
The subject will be asked about any adverse events or changes to medications since the 
last study visit. 
4.2.2 Device preparation 
All Study devices will be time synchronized and checked for function as described in section 
5.3. 
4.2.3 Sensor Insertions 
Each subject will have the Sensors inserted at Visit 2 (Day 0); above the elbow of their arms. 
The study team will prepare the Sensor insertion site appropriately. The hair at the insertion 
area may be clipped in order to ensure appropriate visualization of the insertion site. The 
Sensor will be prepared by qualified personnel (Sponsor personnel or trained investigative 
staff). 
A trained study clinician will insert the Sensor into the subcutaneous tissue using appropriate 
technique described in the Eversense CGM Sensor Insertion and Removal Instructions and 
the Study Operations Manual. The training and qualifications of the clinician performing the 
insertion procedure will be documented.  The location of each Sensor will be documented.  

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Subjects will be advised that they may take over the counter pain medication if needed for 
any discomfort after the insertion process. No medication, including medication-containing 
creams and patches is to be applied over the sensor insertion site. 
Subjects will be advised to keep the area dry for 24-48 hours.  Subjects will be advised to 
change the dressing approximately 48 hours post insertion and they will check that the 
healing process is going as expected (minor redness, no swellings, no increased temperature, 
no increased pain and no sign of infection).  After 48 hours subjects will be advised to change 
the dressing as required until the wound is closed.  Cleaning can be done with normal saline 
in the clinic, but at home they can use tap water from a running tap.  
Identification of the Sensor, Transmitter and accessories will be recorded (part number, 
serial number, lot number, and expiration date as applicable). 
After sensor insertion, the transmitters will be worn briefly (approximately 20 minutes) to 
ensure proper operation of the system (confirmation of system operation).   
4.2.4 Dexamethasone blood draw 
Blood samples for dexamethasone measurement will be drawn as follows: 
o Designated subset of subjects 
 Approximately 30-60 minutes after sensor insertion is complete 
 2 additional samples, timing to be specified, within approximately 4 hours of 
the sensor insertion. 
o All remaining subjects 
 One sample drawn based on analysis of dexamethasone from subset group. 
All samples will be collected and processed as described in the operations manual. 
4.2.5 Device disbursement 
Subjects will be assigned the following devices: 
• Senseonics Continuous Glucose Monitoring (CGM) Systems consisting of- 
o One Gen 1 Transmitter and accessories (charger, adhesive patches)- PRIMARY- Displays 
glucose 
o One Gen 2 Transmitter and accessories (charger, adhesive patches)-  SECONDARY - Does 
not display glucose (subjects  inserted with one sensor only will not use this system) 
o Handheld Device (1 per Subject) running the Mobile Medical Application (MMA) 
o Eversense CGM User Guides 

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• A widely-used, commercially available FDA-approved self-monitoring blood glucose (SMBG) 
meter and associated supplies- 
o BG meter strips 
o Lancets 
o control solution 
o Instructions for Use 
4.2.6 Subject training 
Subjects will be issued one or two transmitters as applicable.   Gen 1 and Gen 2 transmitters 
will be visually distinguishable from each other to ensure matching to the correct limb. 
Subjects participating in the subset for additional dexamethasone testing will only be issued 
the Gen 1 transmitter. Each transmitter is linked to a specific sensor as described in the 
Eversense CGM User Guide. Subjects will be issued a hand held device which will be used for 
entering calibration information into the Gen 1 transmitter only. The Gen 2 transmitter worn 
on the opposite arm will have the ability to collect and log data only and will not calculate 
and store glucose information.   
The subject will be given instructions on how to contact study staff for 24 hours per day to 
report any study- related problems.  The subject will be instructed to contact the study staff 
for prolonged hyperglycemia, severe hypoglycemia, or if he/she experiences nausea, 
vomiting, or abdominal pain within 48 hours after discharge. The subject will be instructed to 
contact the study staff for any problems related to the sensor sites, including fever, pain, 
redness, itching, discharge, warmth or swelling at the sensor insertion sites. If infection is 
experienced, standard medical practice and administration of antibiotics as required should 
be followed until resolution. Subjects will be further instructed to advise the investigator if 
new medications have been prescribed or started, or if any hospitalizations or significant 
medical changes have occurred. 
The subject will be instructed on the proper use and quality control of the Subject SMBG 
Meter including the number and timing of fingersticks expected during each day 
(approximately 7 times per day (before meals, approximately 2 hours after meals, and at 
bedtime)).   
The subject will be instructed on the proper use of the Transmitter and Mobile Medical 
Application (refer to the Eversense CGM User Guides). The transmitter will be worn over the 
sensor at all times (except while charging, bathing or during any other water activities) 
starting approximately 24 hours post insertion. Subjects will be prompted to calibrate the 
sensor using fingerstick measurements (a minimum of 2 each day, approximately 12 hours 
apart) using the Subject SMBG meter.   

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Training may continue at Visit 3, or as needed. 
4.2.7 Discharge 
Discharge will occur upon completion of confirmation of system operation and subject 
training. The site will document any adverse events that may have occurred during the visit. 
When subjects leave the clinic after completing the sensor insertion/training visit, they will 
NOT bring the transmitters or study-supplied meter home with them. Transmitters and 
study-supplied meters will remain at the site overnight and issued to the subject for home 
use at visit 3. Subjects may take the HHD home with them overnight in order to pair with 
their home wifi, and to familiarize themselves with the MMA. 
4.2.8 Estimated Total Blood Volume 
The total amount of blood will not exceed 12 ml plus fingersticks taken during the visit.  
4.2.9 Estimated Visit Duration 
The  total  duration  of  the  inpatient  visit  is  approximately  2-6  hours. 
4.3 
Subset of subjects for dexamethasone analysis 
A designated subset of a minimum of 6 and a maximum of 9 subjects across the study will 
return on days 3-6 for blood draws (~ 4 mL each) for dexamethasone analysis. These samples 
are in addition to the samples collected at visit 3 on days 1 and 2 and at visit 4 on days 7 and 
8 (as described below). 
Dexamethasone results from these subjects will be used to determine whether and when the 
remaining subjects will need to come in for an additional blood draw for dexamethasone 
measurement. This may occur within several hours of sensor insertion (at the end of Visit 2), 
or during the first 7 days post sensor insertion. 
4.4 
Sensor Accuracy (Sampling) Visit 3 – Day 1 (± 0 Days) 
Approximate visit duration - 19 hours 
Approximate sampling duration – 16 hours 
 
 
 
 
 
 
 
 
 
 
 

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Approximate visit timeline: 

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Approximate 
time 
Activity 
~Time relative to first 
IV sample 
~16:00   
Admission and First Calibration  
T=0 -2:00 
~16:30 
Blood draw for dexamethasone 
T=0 -1:30 
~17:00 
Fingerstick 
T=0 -1:00 
~17:15-17:45 Period for glucose stabilization  
T=0 -0:45 - -0:15 
~18:00 
First IV blood sample drawn/ second 
calibration 
T=0 0:00 
~18:00 – 0:00 For qualifying subjects, hyperglycemia 
challenge to achieve hyperglycemia to 
goal glucose >350 mg/dL.  
• Sampling @ 5 min when glucose ≥ 
325 mg/dL, with a target duration 
of 1 hour.  
• Challenge may be stopped once 12 
samples ≥325 mg/dL are collected. 
T=0 0:00 – +6:00 
19:00 
Fingerstick 
T=0 0:00 - +1:00 
~20:00 
Third calibration 
T=0 0:00 - +2:00 
21:00 
Fingerstick 
T=0 0:00 - +3:00 
~22:00 
Fourth calibration 
T=0 0:00 - +4:00 
~23:00 
Fingerstick 
T=0 0:00 - +5:00 
~0:00 
Fingerstick 
T=0 0:00 - +6:00 
~0:00-07:00 
Overnight period 
• Overnight period. Sampling q 15 min 
when glucose is > 75 mg/dL and < 
325 mg/dL. Q 5 minutes when 
outside this range. 
 
T=0 +6:00 - +13:00 
~07:00 
CGM system calibration 
T=0 +13:00 
 

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Approximate 
time 
Activity 
~Time relative to first 
IV sample 
~07:00-10:00 For qualifying subjects, hypoglycemia 
challenge to achieve hypoglycemia target 
<60 mg/dL.  
• Sampling q 5 min when glucose ≤ 
75mg/dL.  
• Target 24 YSI values <75 mg/dL, 
including 6 YSI values <60 mg/dL at 
q 5 min before rescue.  
• Subjects fed low glycemic morning 
meal and YSI data collection 
discontinued once challenge is 
concluded.  
• Hourly fingersticks from 07:00 to 
11:00. 
T=0 +13:00 - +16:00 
~08:00 
Fingerstick 
T=0 +13:00 - +14:00 
~09:00 
Fingerstick 
T=0 +13:00 - +15:00 
~10:00 
Fingerstick 
T=0 +13:00 - +16:00 
~10:00-11:00 Discharge preparation 
T=0 +16:00 - +17:00 
~10:30 
Blood draw for dexamethasone 
T=0 +16:30 
~11:00 
Discharge 
T=0 +17:00 
 
4.4.1 Device preparation 
All Study devices will be time synchronized and checked for function as described in section 
5.3. 
4.4.2 Medications and Medical Supplies 
Medications and medical supply status will be checked as described in Section 5.2. 
4.4.3 Meals 
Other than during glucose challenges, subjects will be allowed to eat, drink and continue 
his/her diabetes treatment regimen throughout the admission. Specific information 
regarding subject meals is described in Section 5.13. 

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4.4.4 Subject Instructions prior to admission 
Prior to admission, subjects should take their medications and food as follows: 
• Subjects participating in hyperglycemia challenge soon after admission should not take 
subcutaneous bolus insulin approximately 3 hours prior to the challenge. Subjects should 
take their normal dose and timing of basal insulin. If challenge subjects need to eat or 
take insulin for safety reasons, they should inform study staff of this information on 
arrival to the clinic. 
• If subjects blood glucose is <150 mg/dL they should be instructed to eat a snack prior to 
coming to the clinic, and be given specific instructions how to modify basal infusion until 
they arrive at the study site. Subjects may receive guidance from study staff trained in 
diabetes treatment regarding insulin and carbohydrate intake prior to the visit. 
4.4.5 Subject Admission 
The subject will arrive at the clinic during the day, no later than approximately 16:00 and the 
following tests will be performed to confirm eligibility for participation in visit 3: 
• Hematocrit will be assessed using local lab or Point of Care testing device. Subject must 
be within reference range to participate in accuracy (sampling) visit. 
• Female subjects of childbearing capacity will perform a urine pregnancy test. If positive, 
the subject will discontinue study participation. Subject withdrawal will be documented. 
• The study team will confirm the absence of a febrile or vomiting illness within 24 hours of 
the admission. 
• The study team will confirm that the subject brought his/her personal insulin and insulin 
pump or injection supplies (as applicable) and required medications. The subject will 
continue to use his/her diabetes treatment regimen throughout the admission. The 
subject will be rescheduled if he/she did not bring his/her required medications or 
appropriate medications are not available at the clinic.  
• Clinical staff to confirm that the transmitters and hand held device are in communication 
and functioning. 
• If all admission readiness criteria are not met, the subject will be rescheduled. If all of the 
admission readiness conditions are met, the subject will be admitted to the Clinical 
Research Unit. NOTE: If rescheduling is required, Clinicians should make every effort to 
reschedule the visit within 1-3 days from the originally scheduled visit.  Rescheduling of 
Visit 3 for safety reasons will not be considered a protocol deviation. 
4.4.6 Adverse events 
Upon admission subject will be asked about any adverse events or changes to medications 
since the last study visit. Adverse events will be documented on the appropriate eCRF. 

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4.4.7 Dexamethasone blood draw 
Blood sample will be drawn at the beginning of the visit, and again at the end of the visit 
prior to discharge for dexamethasone measurement.  All samples will be collected and 
processed as described in the operations manual. 
4.4.8 Ketone testing 
On arrival to the clinic, subject blood ketones should be evaluated from capillary blood using 
the ketone meter. If ketones are ≥0.6 mmol/L, ketone testing should be repeated as 
described in Section 5.8 and subjects should be treated for ketones following ketone 
treatment guidelines Section 7.1.5. 
4.4.9 SMBG testing 
During in-clinic days, subjects should continue testing blood sugar using the study-supplied 
Subject SMBG Meter following the study visit timeline (hourly, except during overnight 
period). 
4.4.10 IV placement 
Intravenous (IV) access appropriate for blood drawing and potential intravenous rescue 
(such as dextrose or glucagon) will be established following the IV placement guidelines 
(Section 5.9) 
4.4.11 Blood sampling for glucose measurement 
Once IV access has been established, blood will be sampled for bedside reference glucose 
every 5-15 minutes per the Blood Sampling guidelines (Section 5.9). 
  
4.4.12 Hyperglycemia Challenge  
For qualifying subjects, a hyperglycemia challenge will be conducted to achieve a glucose 
goal of >350 mg/dL. Sampling interval will be q 5 min when glucose ≥325 mg/dL for a target 
of 1 hour before rescue. For those subjects not following a basal/bolus routine on MDI or 
CSII, glucose control will be free range. Details regarding conduct of the hyperglycemia 
challenge can be found in Section 5.12. 
4.4.13 Hypoglycemia Challenge  
For qualifying subjects, a hypoglycemia challenge will be conducted to achieve a glucose goal 
of ≤60 mg/dL. Sampling interval will be q 5 min when glucose ≤ 75 mg/dL for a target of 2 
hours before rescue. For those subjects not following a basal/bolus routine on MDI or CSII, 
glucose control will be free range. Details regarding conduct of the hypoglycemia challenge 
can be found in Section 5.12. 
4.4.14 Observation subjects  
Subjects with gastroparesis or those subjects unable to participate in glucose challenges will 
participate in the sampling sessions using free range glucose control. 

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4.4.15 Discharge instructions 
The discharge procedure will occur upon completion of ~approximately 16 hours of IV blood 
sampling. Discharge instructions are detailed in Section 5.14.  
4.4.16 Estimated Total Blood Volume 
Approximately 89 blood samples will be obtained throughout the course of the visit in 
addition to the blood sample required for dexamethasone analysis and fingersticks taken. 
The maximum estimated amount of blood estimated for the visit is 97 ml. 
4.4.17 Estimated Visit Duration 
The  total  duration  of  the  inpatient  visit  is  approximately  19  hours.  The study time may 
be extended for glucose stabilization prior to discharge. 
4.5 
Sensor Accuracy (Sampling) Overnight Visits 
 
Visit 4 – Day 7 Accuracy (Sampling) Visit (±1 Day) 
Visit 5 – Day 14 Accuracy (Sampling) Visit (±1 Day) 
Approximate visit duration – 18 hours 
Approximate sampling duration – 16 hours 
 
Approximate visit timeline: 
Approximate 
time 
Activity 
Time relative to first IV 
sample 
~17:00 
Admission 
T=0 -1:00 
~17:15-17:45 
Period for glucose stabilization and CGM 
calibration 
T=0 -0:45 - -0:15 
~17:30 
Blood draw for dexamethasone, prior to YSI 
sampling 
 
~18:00 
First IV blood sample drawn 
T=0 0:00 
~18:00 – 0:00 
• For qualifying subjects, hyperglycemia 
challenge to achieve hyperglycemia to 
goal glucose >350 mg/dL.  
• Sampling @ 5 min when glucose ≥ 325 
mg/dL, with a target duration of 1 hour.  
• Challenge may be stopped once 12 
samples ≥325 mg/dL are collected.  
 
T=0 0:00 – +6:00 
~19:00 
Fingerstick blood glucose 
T=0 +1:00 
~20:00 
Fingerstick blood glucose 
T=0 +2:00  
~21:00 
Fingerstick blood glucose 
T=0 +3:00  

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Approximate 
time 
Activity 
Time relative to first IV 
sample 
~22:00 
Fingerstick blood glucose 
T=0 +4:00  
~23:00 
Fingerstick blood glucose 
T=0 +5:00  
~0:00 
Fingerstick blood glucose 
T=0 +6:00  
~0:00-07:00 
• Overnight period. Sampling q 15 min 
when glucose is > 75 mg/dL and < 325 
mg/dL. Q 5 minutes when outside this 
range. 
 
T=0 +6:00 - +13:00 
~07:00 
Fingerstick blood glucose and sensor 
calibration 
T=0 +13:00 
~07:00-10:00 
For qualifying subjects, hypoglycemia 
challenge to achieve hypoglycemia target 
<60 mg/dL.  
• Sampling q 5 min when glucose ≤ 75 
mg/dL.  
• Target 24 YSI values <75 mg/dL including 
6 YSI values <60 mg/dL at q 5 min before 
rescue.  
Subjects fed low glycemic morning meal and 
YSI data collection discontinued once 
challenge is concluded.  
T=0 +13:00 - +16:00 
~08:00 
Fingerstick blood glucose 
T=0 +14:00  
~09:00 
Fingerstick blood glucose 
T=0 +15:00  
~10:00 
Fingerstick blood glucose 
T=0 +16:00  
~10:00-11:00 
discharge preparation 
T=0 +16:00 - +17:00 
~10:30 
Blood draw for dexamethasone after YSI 
sampling complete. 
T=0 +16:30 
~11:00 
Discharge 
T=0 +17:00 
 
The following procedures/instructions will be followed for accuracy (sampling) visits at Visits 4 
and 5: 
4.5.1 Pre-visit phone call 
One to two days prior to the Accuracy (Sampling) Visit, site personnel will contact the subject 
to ensure the subject is in compliance with study device wear.  Subjects will also be advised 
if they are scheduled for a glucose challenge and will be given appropriate instructions 
regarding pre-visit medications and meals. 

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4.5.2 Device preparation 
All Study devices will be time synchronized and checked for function as described in section 
5.3  
4.5.3 Medications and Medical Supplies 
Medications and medical supply status will be checked as described in Section 5.2. 
4.5.4 Meals 
Specific information regarding subject meals is described in Section 5.13. Food and drink will 
be controlled as required. 
4.5.5 Subject Instructions prior to admission 
Prior to admission, subjects should take medications and meals as usual as follows: 
• Subjects participating in hyperglycemia challenge soon after admission should not take 
subcutaneous bolus insulin approximately 3 hours prior to the challenge. Subjects should 
take their normal dose and timing of basal insulin. If challenge subjects need to eat or 
take insulin for safety reasons, they should inform study staff of this information on 
arrival to the clinic. 
• If subjects blood glucose is <150 mg/dL they should be instructed to eat a snack prior to 
coming to the clinic, and be given specific instructions how to modify basal infusion until 
they arrive at the study site. 
4.5.6 Subject Admission 
The subject will arrive at the clinic during the day, no later than approximately 17:00 and the 
following tests will be performed to confirm eligibility for participation in visits 4 and 5: 
• Hematocrit will be assessed using local lab or Point of Care testing device. Subject must 
be within reference range to participate in accuracy (sampling) visit. 
• Female subjects of childbearing capacity will perform a urine pregnancy test. If positive, 
the subject will discontinue study participation. Subject withdrawal will be documented. 
The study team will confirm the absence of a febrile or vomiting illness within 24 hours of 
the admission. 
• The study team will confirm that the subject brought his/her personal insulin and insulin 
pump or injection supplies (as applicable) and regular medications. The subject will 
continue to use his/her diabetes treatment regimen throughout the admission. The 
subject will be rescheduled if he/she did not bring his/her regular medications or 
appropriate medications are not available at the clinic.  
• Clinical staff to confirm that the subject is wearing the transmitters and that the 
transmitters and hand held device are in communication and functioning. 

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• The subject will be rescheduled if he/she did not bring his/her Transmitters and cannot 
make them available during the visit. 
• If all admission readiness criteria are not met, the subject will be rescheduled. If all of the 
admission readiness conditions are met, the subject will be admitted to the Clinical 
Research Unit. 
4.5.7 Adverse events 
Upon admission subject will be asked about any adverse events or changes in medication 
since the last study visit. The sensor insertion site will be examined. Adverse events including 
those associated with the insertion site will be documented on the appropriate eCRF. 
4.5.8 Dexamethasone blood draw 
Blood sample will be drawn at the beginning of the visit and prior to discharge for 
Dexamethasone measurement. All samples will be collected and processed as described in 
the operations manual. 
4.5.9 Ketone testing 
On arrival to the clinic, subject blood ketones should be evaluated from capillary blood using 
the ketone meter. If ketones are ≥0.6 mmol/L, ketone testing should be repeated as 
described in Section 5.8 and subjects should be treated for ketones following ketone 
treatment guidelines Section 7.1.5. 
4.5.10 SMBG testing 
During in-clinic days, subjects should continue testing blood sugar using the study-supplied 
Subject SMBG Meter following the visit schedule (hourly except during overnight period).  
4.5.11 IV placement 
Intravenous access appropriate for blood drawing and potential intravenous dextrose or 
other medically necessary and appropriate rescue will be established following the IV 
placement guidelines (Section 5.9). 
4.5.12 Blood sampling for glucose measurement 
Once IV access has been established, blood will be sampled for bedside reference glucose 
every 5-15 minutes per the Blood Sampling guidelines (Section 5.9). 
  
4.5.13  Calibration (Visits 4 & 5) 
Subjects/clinicians will calibrate the system during the time period for glucose stabilization 
and will calibrate again approximately 12 hours later. The morning calibration reminder, 
adjusted through use of the HHD and mobile medical application will be set to approximately 
12 hours after the evening calibration entry.   

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4.5.14 Glucose Challenges 
Qualifying subjects will participate in hyperglycemia and hypoglycemia challenges during the 
times indicated in the visit timeline table. The intention of the hypoglycemia and 
hyperglycemia challenge is to safely manipulate the subject’s blood glucose levels so that 
sensor performance can be evaluated over a wider range than might otherwise be observed. 
Details regarding the glucose challenges can be found in Section 5.12.  
4.5.15 Observation subjects  
Subjects with gastroparesis or those subjects unable to participate in glucose challenges will 
participate in the sampling sessions using free range glucose control.   
4.5.16 Sleep Assessment 
Designated subjects will be inserted with two sensors, one in each upper arm.  Each subject 
will spend two overnights in the clinic where they will be instructed to sleep on one side for 
situations in which compression of the sensor site may occur during sleep.  “Sensor drop-
out,” if a phenomenon of the Senseonics CGM System, will be identified during these 
periods. Sleep position will not be documented. 
4.5.17 Discharge instructions 
The discharge procedure will occur upon completion of IV blood sampling. Please refer to 
section 5.14 for discharge instructions. 
4.5.18 Estimated Total Blood Volume 
Approximately 89 blood samples will be obtained throughout the course of the respective 
visits in addition to the blood sample required for dexamethasone analysis and fingersticks 
taken. The maximum estimated amount of blood estimated for each visit is 97 ml. 
4.5.19 Estimated Visit Duration 
The total duration of the inpatient visit is approximately 18 hours.  The study time may be 
extended for glucose stabilization prior to discharge. 
 
4.6 
Sensor Accuracy (Sampling) Daytime Visits 
 
Visit 6 – Day 30 Accuracy (Sampling) Visit (±7 Days) 
Visit 7 – Day 60 Accuracy (Sampling) Visit (±7 Days) 
Visit 8 – Day 90 Accuracy (Sampling) Visit (-3/+7 Days) 
Approxim
ate Visit 
Approximate 
Sampling 
Visit 6 (Day 30 ±7 Days) 
14 hours 
12.5 hours 
Visit 7 (Day 60 ±7 Days) 
14 hours 
12.5 hours 

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Visit 8 (Day 90 -3/+7 Days) 
15 hours 
12.5 hours 
 
Approximate visit timeline: 
Approximate 
time 
Activity 
Time relative to first IV 
sample 
~07:00 
Admission  
T=0 -1:00 
~07:15-07:45 
Period for glucose stabilization and CGM 
calibration 
T=0 -0:45 - -0:15 
~08:00 
First IV blood sample drawn 
T=0 0:00 
~08:00 – 
13:00 
For qualifying subjects, hypoglycemia 
challenge to achieve hypoglycemia target 
<60 mg/dL.  
• Sampling q 5 min when glucose ≤ 75 
mg/dL.  
• Target 24 YSI values <75 mg/dL including 
6 YSI values <60 mg/dL at q 5 min before 
rescue.  
• Subjects fed low glycemic meal.  
T=0 0:00 – +5:00 
~08:00 – 
13:00 
• Alternatively, for qualifying subjects, 
hyperglycemia challenge to achieve 
hyperglycemia to goal glucose >350 
mg/dL.  
• Sampling @ 5 min when glucose ≥ 325 
mg/dL, with a target duration of 1 hour.  
• Challenge may be stopped once 12 
samples ≥325 mg/dL are collected.  
 
T=0 0:00 – +5:00 
~08:00 – 
13:00 
For those subjects not following a basal/bolus 
routine on MDI or CSII, glucose control will be 
free range. 
T=0 0:00 – +5:00 
~09:00 
Fingerstick blood glucose 
T=0 +1:00  
~10:00 
Fingerstick blood glucose 
T=0 +2:00  
~11:00 
Fingerstick blood glucose 
T=0 +3:00  
~12:00 
Fingerstick blood glucose 
T=0 +4:00  
~13:00 
Fingerstick blood glucose 
T=0 +5:00  
~13:00-16:00 
Recovery Period with meal/bolus and glucose 
stabilization 
T=0 +5:00 - +8:00 
~16:00-19:30 
Free range glucose control 
T=0 +8:00 - +11:30 
~14:00 
Fingerstick blood glucose 
T=0 +6:00  
~15:00 
Fingerstick blood glucose 
T=0 +7:00  

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Approximate 
time 
Activity 
Time relative to first IV 
sample 
~16:00 
Fingerstick blood glucose 
T=0 +8:00  
~17:00 
Fingerstick blood glucose 
T=0 +9:00  
~18:00 
Fingerstick blood glucose 
T=0 +10:00  
~19:00 
Fingerstick blood glucose 
T=0 +11:00  
~19:30-20:30 
Discharge preparation period 
T=0 +11:30 - +12:30 
~20:00 
Blood draw for dexamethasone  
T=0 +12:00 
~20:30 
Last IV blood sample drawn 
T =0 + 12:30 
21:00 
Discharge 
T=0 +13:00 
 
The following procedures/instructions will be followed for accuracy (sampling) daytime 
visits at days 30, 60 and 90: 
4.6.1 Pre-visit phone call 
One to two days prior to the Accuracy (Sampling) Visit, site personnel will contact the subject 
to ensure the subject is in compliance with study device wear.   Subjects may also be advised 
of the scheduled challenge type and will be given appropriate instructions regarding pre-visit 
medications and meals. 
4.6.2 Device preparation 
All Study devices will be time synchronized and checked for function as described in section 
5.3.  
4.6.3 Medications and Medical Supplies 
Medications and medical supply status will be checked as described in Section 5.2. 
4.6.4 Meals 
Specific information regarding subject meals is described in Section 5.13. Food and drink will 
be controlled as required. 
4.6.5 Subject Instructions prior to admission 
Prior to admission, subjects should take morning medications and meals as usual as follows: 
• If challenge subjects need to eat or take insulin for safety reasons, they should inform 
study staff of this information on arrival to the clinic. 
• Subjects participating in hypoglycemia challenges should arrive fasted for 6 hours and 
should not take subcutaneous bolus insulin 3-4 hours previous to the challenge. Subjects 
should take their normal dose and timing of basal insulin. 
• If subjects blood glucose is <80 mg/dL they should be instructed to eat a snack prior to 

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coming to the clinic, and be given specific instructions how to modify basal infusion until 
they arrive at the study site. Subjects may receive guidance from study staff trained in 
diabetes treatment regarding insulin and carbohydrate intake prior to the visit. 
 
• Subjects should consume the food they would normally consume to treat or prevent 
hypoglycemia at the blood glucose level they feel is appropriate. 
A clinician trained in the treatment of diabetes should also discuss and make 
recommendations about each subject’s insulin regimen for the remainder of the day to 
prevent post-visit rebound hypoglycemia which can occur 12 hours later. 
4.6.6 Subject Admission 
The subject will arrive at the clinic during the day, no later than approximately 07:00 am and 
the following tests will be performed to confirm eligibility for participation in visits 6, 7 and 
8: 
• Hematocrit will be assessed using local lab or Point of Care testing device. Subject must 
be within reference range to participate in accuracy (sampling) visit. 
• Female subjects of childbearing capacity will perform a urine pregnancy test. If positive, 
the subject will discontinue study participation. Subject withdrawal will be documented. 
• The study team will confirm the absence of a febrile or vomiting illness within 24 hours of 
the admission. 
• The study team will confirm that the subject brought his/her personal insulin and insulin 
pump or injection supplies (as applicable) and regular medications. The subject will 
continue to use his/her diabetes treatment regimen throughout the admission. The 
subject will be rescheduled if he/she did not bring his/her regular medications or 
appropriate medications are not available at the clinic.  
• Clinical staff to confirm that the subject is wearing the transmitters and that the 
transmitters and hand held device are in communication and functioning. 
• The subject will be rescheduled if he/she did not bring his/her Transmitters and cannot 
make them available during the visit. 
• If all admission readiness criteria are not met, the subject will be rescheduled. If all of the 
admission readiness conditions are met, the subject will be admitted to the Clinical 
Research Unit. 
4.6.7 Adverse events 
Upon admission subject will be asked about any adverse events or changes in medication 
since the last study visit. The sensor insertion site will be examined. Adverse events including 
those associated with the insertion site will be documented on the appropriate eCRF. 

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4.6.8 Ketone testing 
On arrival to the clinic, subject blood ketones should be evaluated from capillary blood using 
the ketone meter. If ketones are present, ketone testing should be repeated as described in 
Section 5.8 and subjects should be treated for ketones following ketone treatment 
guidelines Section 7.1.5. 
4.6.9 SMBG testing 
During in-clinic days, subjects should continue testing blood sugar using the study-supplied 
Subject SMBG Meter following the schedule for each visit (hourly except during overnight). 
For home use periods, it is requested that subjects test approximately 7 times per day 
(before meals, 2 hours after meals, and at bedtime). Subjects should test their blood sugar 
using the study supplied Subject SMBG Meter at least 2 times per day while participating in 
the study. 
4.6.10 IV placement 
Intravenous access appropriate for blood drawing and potential intravenous DW10 rescue 
will be established following the IV placement guidelines (Section 5.9) 
4.6.11 Blood sampling for glucose measurement 
Once IV access has been established, blood will be sampled for bedside reference glucose 
every 5-15 minutes per the Blood Sampling guidelines (Section 5.9). 
4.6.12 Calibration (Visits 6, 7 & 8) 
Subjects/clinicians will calibrate the system during the time period for glucose stabilization 
and will calibrate again approximately 12 hours later. The morning calibration reminder, 
adjusted through use of the HHD and mobile medical application will be set to approximately 
12 hours after the evening calibration entry.   
4.6.13 Glucose Challenges 
Qualifying subjects will participate in hyperglycemia or hypoglycemia challenges during the 
times indicated in the visit timeline table. The intention of the hypoglycemia and 
hyperglycemia challenge is to safely manipulate the subject’s blood glucose levels so that 
sensor performance can be evaluated over a wider range than might otherwise be observed. 
Details regarding the glucose challenges can be found in Section 5.12.  
4.6.14 Observation subjects  
Subjects with gastroparesis or those subjects unable to participate in glucose challenges will 
participate in the sampling sessions using free range glucose control. 

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4.6.15 Dexamethasone blood draw 
Blood sample will be drawn at the end of the visit prior to discharge for 
Dexamethasone measurement. All samples will be collected and processed as 
described in the operations manual. 
4.6.16 Discharge instructions 
The discharge procedure will occur upon completion of IV blood sampling. Please refer to 
section 5.14 for discharge instructions. 
4.6.17 Estimated Total Blood Volume 
Approximately 59 blood samples will be obtained throughout the course of the respective 
visits in addition to the blood sample required for dexamethasone analysis and fingersticks 
taken. The maximum estimated amount of blood estimated for each visit is 65 ml. 
4.6.18 Estimated Visit Duration 
The total duration of the inpatient visit is approximately 14-15 hours.  The study time may be 
extended for glucose stabilization prior to discharge. 
 
4.7 
Visit 8, Day 90 Sensor Removal 
Sensors will be removed after glucose sampling is complete approximately 90 days post 
insertion, or when the designated time for Sensor removal is reached. If designated time 
for sensor removal is reached prior to Visit 8, the sensor will be removed at the subject’s 
next scheduled visit or at an unscheduled visit. All Visit 8 procedures will be performed as 
applicable. Removal of the sensor may also be scheduled after Visit 8 if more convenient 
for subject and clinicians (but no longer than 100 days post insertion) provided that the 
Subject’s transmitters and HHD have been taken from the Subject at the conclusion of 
Visit 8. Sensor removal before or after Visit 8 will not be considered a protocol deviation 
provided that removal is performed prior to 101 days post insertion and Visit 8 removal 
procedures/activities are followed. Subjects will be asked to complete a questionnaire 
regarding their experiences at the end of sensor wear period.  
Blood samples will be drawn prior to sensor removal for Dexamethasone measurement. 
All samples will be collected and processed as described in the operations manual. 
Prior to Sensor removal, the Investigator will assess the Sensor location, including by process 
of palpation.   The Sensor will be removed following the procedure in the Eversense CGM 
Sensor Insertion and Removal Instructions and the Study Operations Manual. 
 
The removed Sensors will be handled in compliance with institution/regulatory requirements 
for biomedical waste, and will be returned following Senseonics instructions, using the 
provided Biohazard Return Kit. 

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4.8 
Visit 9 –Follow-up Visit (10 days following sensor removal. Window: sensor removal date 
+7 to 17 Days) 
 
The healing of the Sensor sites will be evaluated at this planned final visit. If Sensors are 
removed at a time other than Visit 8, the Follow-up Visit will occur in approximately 10 days 
after Sensor removal. 
If there is a concern by the investigator about healing of the Sensor sites, the subject will be 
asked to return in approximately 10 days, and followed until resolution. Any adverse event 
would be reported. 
Subject will exit the study after the Follow-up Visit is completed as above. Subjects will 
continue to follow their diabetes care routine according to their health care provider 
recommendations. 
 
5 
GENERAL CONSIDERATIONS FOR STUDY VISITS 
 
5.1 
Definition of Enrollment 
A subject is considered enrolled in the clinical trial after he or she has provided informed 
consent.  
 
Subjects who fail one or more of the eligibility criteria are considered screen failures. Subjects 
who withdraw consent or are withdrawn by the investigator after enrollment and prior to 
the first Sensor insertion attempt are “withdrawn prior to Sensor insertion” and are 
withdrawn from the study without data acquisition. A listing of screen failures and 
“withdrawals prior to Sensor insertion” subjects including the reason for study exit will be 
reported. 
 
Subjects who begin a first Sensor insertion procedure (defined as injection of local anesthetic) 
remain enrolled in the study and will be analyzed as evaluable subjects per the description of 
study populations in Section 11 Statistical Methods. 
 
5.2 
Medications and medical supplies 
All medications and medical supplies required for the Clinical Research Center (CRC) 
hypoglycemia and hyperglycemia treatment protocols will be readily available at the time of 
subject treatment including a code cart. The subject will be rescheduled if he/she did not 
bring his/her required medications or appropriate medications are not available at the clinic.   
 
 

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5.3 
Device setup 
5.3.1 Device Calibration 
Prior to subject blood sampling, the CRC study equipment (YSI glucose analyzer, ketone 
meter and study-supplied Subject SMBG Meter) will be checked for proper function and the 
appropriate quality controls will be run per the manufacturer’s guidelines and/or Study 
Operations Manual, as appropriate.  
5.3.2 Time sync 
At each study visit the date and time on all study devices (i.e.  study clocks, laptop(s), Subject 
SMBG Meter, Reference instrument and Senseonics Continuous Glucose Monitoring System) 
will be synchronized at the start of the visit to the Official US Time using www.time.gov or to 
an equivalent atomic clock. The details of the time and date synchronization are described in 
the Study Operations Manual. 
The study devices do not all automatically adjust for daylight savings time. Subjects should 
not adjust the study device times on their own – they should wait until someone at the clinic 
can adjust the time so any offsets can be documented in order to reconcile the data. 
5.3.3 Downloading devices 
The study issued Subject SMBG meter and the sensor transmitters will be downloaded at the 
end of each sensor accuracy visit (visits 3-8) or at any unscheduled   visit as appropriate. 
Sensor transmitter data will also be uploaded to a data management system to monitor 
calibration compliance.  
5.4 
Measurement Devices – Maintenance/Control Testing 
At device disbursement or as appropriate, study equipment (bedside YSI glucose analyzer, 
ketone meter and study-supplied (SMBG) meter) will be checked for proper function and the 
appropriate quality controls will be run per the manufacturer’s guidelines.  
5.4.1 Bedside YSI 
The primary instrument for plasma glucose measurements is the YSI glucose analyzer (2300 
Stat Plus Glucose & Lactate Analyzer, Yellow Springs Instruments, Yellow Springs, OH, USA).  
Manufacturer instructions for operation, calibration, quality control, and maintenance will 
be followed. 
5.4.2 Subject SMBG Meter 
The study will supply and use a widely-used, commercially available FDA-approved self-
monitoring blood glucose (SMBG) meter and strips. Control solution testing of the 
meter/strips will be verified with the control solution(s) specific to the meter and strips. The 
tested control solutions must read within the established range on the glucometer strips per 

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manufacturer labeling in order to be used in the study. Manufacturer instructions for 
operation and quality control will be followed. Subjects will be advised to perform control 
solution testing each time a new package of strips is deployed, or any time the subject 
suspects improper performance of the meter. 
5.4.3 Ketone meter 
The study will supply and use an FDA-approved self-monitoring ketone meter and strips 
(Abbott Precision Xtra or similar), which will measure β-hydroxybutyrate (β-HOB). Ketone 
meters will remain at the clinical site (not disbursed to the subject). Calibration of the ketone 
meter will be verified with the control solution(s) specific to the meter and strips. The tested 
control solutions must read within the established range on the strips per manufacturer 
labeling in order to be used in the study. Manufacturer instructions for operation and quality 
control will be followed. 
5.5 
Senseonics Continuous Glucose Monitoring (CGM) System Calibration 
The  Senseonics  Continuous  Glucose  Monitoring (CGM)  System  will  be  calibrated  and  
maintained  per Eversense CGM User Guide. After the initialization period (approx. 30 hours 
after sensor insertion), the system enters the Daily Calibration phase. For this study, subjects 
should follow the recommendations below: 
5.5.1 At home 
During periods of home use, it is recommended to calibrate the Senseonics CGM System 
using SMBG values from the study-supplied meter two times per day. Calibration is best 
done when glucose is neither rapidly rising nor falling.  Subjects can set morning and evening 
daily calibration reminders and Subjects will be periodically prompted by the Senseonics 
CGM System until a calibration point is entered. 
5.5.2 In clinic 
During the in-clinic sampling sessions, subjects will be instructed to calibrate at the start of 
the sampling session and then approximately 12 hours later unless in the initialization phase.   
5.6 
Use of Study Devices for Diabetes Treatment 
For the duration of the study, all diabetes care decisions will be based on   reference blood 
glucose values or SMBG as appropriate, rather than Senseonics CGM System results. 
5.7 
Fingersticks 
During the study, while at home and in the clinic, it is requested that all subjects test their 
blood sugar using the study supplied SMBG meter approximately 7 times per day (before 
meals, 2 hours after meals, and at bedtime).     Subjects should test their blood sugar using 
the study supplied Subject SMBG Meter at least 2 times per day while participating in the 
study. 

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All fingersticks for capillary blood glucose testing will be preceded by hand washing (with 
soap, warm water and a dry towel), or by using an alcohol swab and allowing the area to air 
dry. 
5.8 
Ketones 
Ketone (β-hydroxybutyrate (β-HOB)) measurements will be made using a study supplied FDA-
approved self-monitoring ketone meter and strips as described in 5.4.3. Subject blood 
ketones should be evaluated from capillary or venous blood using the ketone meter while in 
the clinic for sensor insertion and accuracy (sampling) visits at the following times: 
• On arrival to and at discharge from the clinic  
• Glucose ≥300 mg/dL (measure approximately within 20 minutes of the first glucose 
reading >300 mg/dL and repeat approximately every 60 minutes until < 300mg/dL) 
• Ketones  ≥0.6 mmol/L (repeat approximately every 60 minutes until < 0.6 mmol/L) 
• Subject has nausea, vomiting or abdominal pain regardless of glucose level. 
Treatment guidelines for ketones can be found in section 7.1.5. 
5.9 
IV/Blood Draw Guidelines 
5.9.1 IV Placement/Setup 
IVs for blood sampling may be placed in the arm or hand. IV Access will be maintained during 
the sampling portion of the study for blood sampling and for the treatment of severe 
hypoglycemia or hyperglycemia during the study. If an IV fails, a reasonable effort should be 
made to replace it. 
It is advised that sites use a heating pad in order to help keep IV sampling sites patent and 
improve blood flow. 
Sites will be advised to use a dual stopcock closed-loop or single stopcock blood-wasting 
technique, as long as site personnel are cognizant of the following:  
• The single-stopcock technique has a lower risk of diluted samples, but sites must take 
care not to exceed the protocol total blood loss limit of 475 ml in any 8-week period. 
• Please note that when calculating waste volume to consider the volume of saline in the 
system that is drawn when clearing the line. This could include the extension set (0.2 ml), 
stopcock (0.2ml), and cannula (0.1 ml). Therefore a 1.5 ml “waste” draw actually contains 
1.0 ml blood. 

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5.9.2 Timing of blood sampling 
Blood will be sampled every 5-15 minutes, dependent on the value of the previous sample 
according to the following ranges: 
• BG ≥ 325 mg/dL: every 5 minutes (+/- 2 minutes) 
• BG >75 mg/dL and  < 325 mg/dL: every 15 minutes (+/- 2 minutes) 
• BG  ≤75 mg/dL:  every 5 minutes (+/- 2 minutes) 
 
Additional samples may be drawn for YSI glucose analysis as needed for patient safety or to 
recheck a suspected erroneous value (e.g. dilute sample). 
In the event of loss of IV access or loss of functional YSI and need for continued subject 
monitoring, glucose measurements will be made on capillary whole blood using the Subject 
SMBG meter as needed. These values will not be included in the study data set, but will only 
be used for subject treatment decisions. 
Samples missed due to loss of IV access or loss of functional YSI will not be considered 
protocol deviations.  
5.9.3 Sample volume 
Approximately 1.0 ml IV blood samples will be collected (after saline is cleared from 
sampling apparatus) in sample containers with an appropriate anticoagulant additive (BD 
Microtainer K2E tubes (REF 365955) or Sarstedt Monovette with K2E (REF 06.1664.001) or 
similar) for analysis.  
5.9.4 Centrifuge  
Centrifuge sample to sufficiently separate the plasma, approximately 30 seconds in StatSpin 
Express 2 (or similar) centrifuge (8500 rpm). 
Samples centrifugation should begin as soon as possible after the blood draw (within a 
maximum of 3 minutes).   Spun samples should be prepared, as defined in the Study 
Operations Manual. 
*More detailed guidelines are included in the Study Operations Manual. 
5.10 Sensor Replacement 
For subjects with one sensor (participating in the subset), if sensor failure is suspected, 
sensor will not be replaced.  
For subjects with two sensors, suspect failure of the primary sensor (the sensor for which 
calibration fingersticks are entered), the secondary sensor in the contralateral arm will 
become the primary sensor. Subjects will be instructed to replace the Gen 2 transmitter with 

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the Gen 1 transmitter in the contralateral arm. The suspect failed primary sensor will not be 
replaced and will be removed at the end of the study. Subjects will proceed with the next 
regularly scheduled visit. For the suspect failure of the secondary sensor, the sensor will be 
removed at the end of the study and not replaced.  
5.11 Sponsor Presence at Visits 
One or more technical representatives of the sponsor may be present during clinic visits 
under supervision of the Clinical Investigator. 
 
5.12 Glucose challenges  
The intention of the hypoglycemia and hyperglycemia challenge is to safely manipulate the 
subject’s blood glucose levels so that sensor performance can be evaluated over a wider 
range than might otherwise be observed. The intentions are to induce the following: 
Hypoglycemia challenge  
Range 
Duration (approximate) 
Estimated number of paired points 
per subject per challenge 
<60 mg/dL 
30 minutes 
7 
<75 mg/dL 
120  minutes (including 30 minutes <60 
mg/dL) 
25 
 
Hyperglycemia challenge  
Range 
Duration (approximate) 
Estimated  number of paired points 
per subject per challenge 
>325mg/dL 
60 minutes 
13 
>180 mg/dL 
120 minutes (including 60 minutes 
>325 mg/dL) 
17 
 
It is the intent of this protocol to induce a hyperglycemic protocol upon admission to the 
clinic for visits 3, 4 & 5.  Subjects participating in hyperglycemia challenge soon after 
admission should not take subcutaneous bolus insulin approximately 3-4 hours prior to the 
challenge. Subjects should take their normal dose and timing of basal insulin. If challenge 
subjects need to eat or take insulin for safety reasons, they should inform study staff of this 
information on arrival to the clinic. 
5.12.1 Subject eligibility 
Subjects with gastroparesis will not be eligible to participate in glucose challenges. Subjects 
not on insulin therapy will not be expected to undergo hypoglycemic challenges.  Eligible 
subjects will be required to participate in glucose challenges.   

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5.12.2 Challenge periods (Visits 3, 4 & 5) 
Subject blood glucose level as measured by the first   blood glucose sample reading will 
determine whether or not the subject will begin the hyperglycemia challenge.  If blood 
glucose is <180 mg/dL the glucose sampling period may be delayed until blood glucose is 
brought into range.  
5.12.3 Determining which challenge to choose (Visits 6, 7 & 8) 
Subject BG level as measured by the first blood glucose sample reading will determine 
whether or not the subject will participate in the hypoglycemia or hyperglycemia challenge 
on that study day, according to the following table: 
Glucose level 
Challenge 
<180 mg/dL 
Hypoglycemia challenge 
≥180 mg/dL 
Hyperglycemia challenge 
5.12.3.1 Hyperglycemia Challenge Guidelines 
Glucose level 
Insulin 
administration  
Glucose 
administration 
(challenge initiation) 
Duration* 
(Approx.) 
Safety 
  <180 mg/dL 
None. Glucose 
sampling period 
may be delayed 
until blood glucose 
is brought into 
range (>180 mg/dL). 
Administer 
carbohydrates to 
gradually bring 
blood glucose into 
range (>180 mg/dL). 
 
 
180 mg/dL to 
325 mg/dL 
None 
Administer meal of 
known carbohydrate 
content (and SQ 
insulin if 
appropriate, see 
mixed meal 
examples in the 
table in 5.11), 
targeting glucose 
level of 350 mg/dL 
based on subject’s 
insulin/carbohydrate 
ratio. Do not 
withhold insulin >2-
3 hours. 
2 hours 
(including 
approx, 60 
minutes 325-
400 mg/dL) 
Check/treat 
for ketones if 
subject BG 
>300mg/dL. 
Treat ketones 
according to 
the 
Hyperglycemia 
and Ketone 
Treatment 
Section 7.1.5 

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Glucose level 
Insulin 
administration  
Glucose 
administration 
(challenge initiation) 
Duration* 
(Approx.) 
Safety 
>325mg/dL 
to 400 mg/dL 
After approximately 
60minutes in this 
range and achieving 
the targeted 
number of points, 
administer SQ fast-
acting insulin 
targeting 120 mg/dL 
based on subject’s 
insulin sensitivity 
ratio. Insulin may 
not be delivered or 
repeated unless 
approximately 3 
hours after previous 
dose.  
None 
60 minutes 
Check/treat 
for ketones if 
subject BG 
>300 mg/dL. 
Treat ketones 
according to 
the 
Hyperglycemia 
and Ketone 
Treatment 
Section 7.1.5 
>400 mg/dL 
Administer SQ fast-
acting insulin 
targeting 120 mg/dL 
based on subject’s 
insulin sensitivity 
ratio. Insulin may 
not be delivered or 
repeated unless 3 
hours after previous 
dose. 
None 
 
Check/treat 
for ketones if 
subject BG 
>300 mg/dL. 
Treat ketones 
according to 
the 
Hyperglycemia 
and Ketone 
Treatment 
Section 7.1.5 
*Once Hyperglycemia challenge durations have been met (120 minutes >180 mg/dL including 60 
minutes >325 mg/dL), the challenge should be ended by administering SQ fast-acting insulin 
targeting 120-150 mg/dL based on subject’s insulin sensitivity ratio.  Once the subjects’ BG is 
normal, glucose control will be free range. If additional carbohydrates are required to reach 
challenge goals, they may be administered. 
5.12.3.2 Hypoglycemia challenge guidelines 
Glucose 
level 
Insulin administration 
(challenge initiation) 
Glucose 
administration 
Duration* 
(Approx.) 
Safety 
<60 mg/dL 
None 
After 30 minutes 
and targeted points 
achieved, treat 
30 
minutes 
If subject is 
unable to ingest 
glucose orally, IV 

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Glucose 
level 
Insulin administration 
(challenge initiation) 
Glucose 
administration 
Duration* 
(Approx.) 
Safety 
hypoglycemia using 
glucose tablets   (15 
g. and check in 15 
minutes, repeat) 
until BG >60 mg/dL 
dextrose may be 
used. Glucagon 
will be available 
for emergency. 
60 – 75 
mg/dL 
None 
None 
120 
minutes 
(including 
30  
minutes 
below 60 
mg/dL) 
 
> 75 but 
<180 mg/dL 
SQ fast-acting insulin 
to be delivered 
targeting 60 mg/dL 
based on subject’s 
insulin sensitivity 
ratio. Bolus insulin 
may not be delivered 
or repeated unless 3 
hours after previous 
dose. 
None 
 
 
*Once Hypoglycemia challenge durations have been met (120 minutes <75 mg/dL including 30 
minutes <60 mg/dL), the challenge should be ended by inducing a controlled raising of the subject’s 
BG to the normal range (75-120 mg/dL) using glucose tablets or food. Once the subjects BG is 
normal, glucose control will be free range. 
 
5.13 Example Meal Choices 
The following meal choices are examples that may be used during clinic visits 3-8. 
 
Meal Choice 1 
Description 
Portion 
Size  
Carbohydrate 
(g) per portion 
Sugar 
(g) per 
portion  
Protein 
(g) per 
portion 
Fat (g) per 
portion 
Fiber (g) per 
portion 
6” sub roll or flat 
bread 
Acceptable 
substitute: 2 large 
slices of whole grain 
sandwich bread 
Ex: Subway 
wheat roll or 
multigrain 
flatbread 
 
71g 
40 
5 
7 
2 
5 
4 oz. ham, turkey, 
chicken, beef  (this 
would be “double 
Subway or 
similar deli 
cuts 
112g 
4 
1 
28 
2-8g 
depending 
upon 
choice 
0 

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Meal Choice 1 
Description 
Portion 
Size  
Carbohydrate 
(g) per portion 
Sugar 
(g) per 
portion  
Protein 
(g) per 
portion 
Fat (g) per 
portion 
Fiber (g) per 
portion 
meat” for subway 6” 
sub)   
1 oz. cheese 
Ex: Swiss, 
monteray jack, 
provolone, 
American, 
cheddar 
28g 
0 
0 
6 
10 
0 
Lettuce, 2-3 slices 
tomato 
Additional 
vegetables or small 
salad acceptable 
- 
41 
2 
0 
0 
0 
1 
1 Tbsp mayonnaise, 
2 T lite mayo or 1 
Tbsp oil 
Varies  
15 
0 
0 
0 
12 
0 
1 1/2 oz. chips – 
whole grain if 
possible 
Ex:  Sunchips 
at Subway 
43 
29 
3 
4 
9 
3 
1 ½ oz cookie  - OR-  
Ex: Choc Chip 
at Subway 
45 
30 
18 
2 
10 
1 
Medium piece of 
fresh fruit or 
equivalent 
Ex: 2 packages 
of Subway 
apple slices, 8” 
banana 
Varies 
30 
26 
0 
0 
4 
Water or other zero 
calorie beverage 
Ex: water, diet 
coke 
8-16 
oz. 
0 
0 
0 
0 
0 
 
 
 
105 
27-35 
45-47 
35-51 
10-13 
 
Meal Choice 2 
Description 
Portion 
Size  
Carbohydrate 
(g) per portion 
Sugar 
(g) per 
portion  
Protein 
(g) per 
portion 
Fat (g) per 
portion 
Fiber (g) per 
portion 
6 oz. Grilled Chicken  
Ex:  
Applebee’s 
“Create Your 
Masterpiece 
Menu” Grilled 
Chicken Breast 
168g 
or 6 oz. 
2 
0 
42 
4 
0 
9 oz baked potato – 
seasoned 2 tsp 
butter or margarine 
Ex: Applebees 
“Choice of 
Sides” Baked 
Potato 
252g 
or 9 oz.  
41 
0 
6 
24 
3 
Steamed broccoli – 
seasoned lightly 
with butter, 
margarine or oil 
Ex: Applebees 
“Choice of 
Sides” 
Steamed 
Broccoli 
84g 
2 
0 
2 
8 
3 

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Meal Choice 2 
Description 
Portion 
Size  
Carbohydrate 
(g) per portion 
Sugar 
(g) per 
portion  
Protein 
(g) per 
portion 
Fat (g) per 
portion 
Fiber (g) per 
portion 
Dinner Roll – 2 oz. 
Ex: Applebee’s 
kid’s sized 
burger  roll 
56g 
30 
4 
5 
1 
0 
1 tsp butter or 
margarine (for roll) 
– optional 
- 
1tsp 
0 
0 
0 
9 
0 
Medium piece of 
fresh fruit or 
equivalent 
1 8” banana 
2 c. melon 
Varies 
30 
26 
0 
0 
4 
 
 
 
105 
30 
55 
38-46 
10 
 
Low Glycemic 
Breakfast* 
Description 
Portio
n Size  
Carbohydrate 
(g) per portion 
Sugar 
(g) per 
portion  
Protei
n (g) 
per 
portio
n 
Fat (g) per 
portion 
Fiber (g) per 
portion 
2 slices whole grain 
toast 
Preferably 
Whole grain 
28g  
30 
4 
5 
- 
4 
1 tsp butter or 
margarine 
- 
1 tsp 
0 
0 
0 
9 
0 
2 Scrambled Eggs or 
3 Egg Whites – 
prepared with up to 
1 tsp. fat 
 Optional:  
Cheese/veggies 
mixed into eggs 
 
- 
 2 eggs 
 
¼ c.  
0 
 
1 
0 
 
0 
14 
 
2-7 
5-8 
 
0-5 
0 
 
0 
Coffee – if desired 
Limit to 10 oz. 
for caffeine 
10 oz.  
0 
0 
0 
0 
0 
Non-calorie 
sweetener 
- 
User 
prefer
ence 
- 
- 
- 
- 
- 
Up to 2 Tbsp milk or 
cream 
Milk can be 
whole, 1%, 2% 
or skim 
2T 
Negl. 
0 
Negl. 
0-4g 
0 
 
 
 
30-31 
4 
21-28 
14-34 
4 
*Overall Guidelines:  Limit Carbohydrate to 30g. No fruit juice, no milk beyond any used in coffee.    Fruit acceptable up 
to 15g portion.   
 
5.14 Discharge instructions – Sensor accuracy visits 
The discharge procedure will occur upon completion of visit related activities. Blood glucose 
(either SMBG or YSI) and ketone measurements will be assessed. If the glucose level is<75 
mg/dL or ≥300 mg/dL, corrective action will be taken by the investigator as below: 

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• If plasma glucose is <75 mg/dL, carbohydrates or other medically necessary and 
appropriate interventions will be administered to raise the glucose to ≥75 mg/dL.  
• If plasma glucose is >300 mg/dL, fingerstick ketones will be checked and the Inpatient 
Hyperglycemia and Ketone Treatment guidelines will be followed. 
The subject will be discharged once plasma glucose is: 
• 
100-300 mg/dL and stable or rising in this range for 2 consecutive glucose measurements 
at least 15 minutes apart, and ketone is ≤0.6 mmol/L; or  
• 
>75-100 mg/dL and rising for 2 consecutive glucose measurements at least 15 minutes 
apart, and ketone is ≤0.6 mmol/L. 
• 
Subjects should not be released if BG is <100 mg/dL and not rising. 
• 
Site will document any adverse events that may have occurred during the visit. 
*These measurements should be taken after approximately 60-90 minutes since the last 
administration of fast-acting bolus insulin.  
Additional inpatient time for BG stabilization will not be considered an adverse event or 
protocol deviation. 
Subjects will be provided a standard meal or snack as necessary during the last hour of visit 
prior to release to prevent post-discharge hypoglycemia. Snacks will be available in the clinic 
for subjects to take with them on the ride home. 
A clinician trained in the treatment of diabetes should also discuss and make 
recommendations about each subject’s insulin regimen for the remainder of the day to 
prevent post-visit rebound hypoglycemia which can occur 12 hours later. 
 
5.15 Photograph/Videography 
The procedure for inserting or removing the sensors  may be photographed and/or recorded 
on video after receiving subject authorization in writing. Only the area immediately nearby 
the sites will be photographed and/or recorded and subjects will not be identifiable. 
 
 
6 
CLINICAL LABORATORY EVALUATIONS AND ESTIMATED BLOOD VOLUMES 
 
Standard clinical laboratory analysis equipment, procedures and quality control will be used for 
all laboratory evaluations in this clinical trial. Blood samples will be drawn at Visits 1 through 8 
(or sensor removal as appropriate) for laboratory dexamethasone measurement.  Additionally 
designated subjects across the study will have blood samples drawn for dexamethasone 

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measurement 3 times on the insertion date, and on each day between visits 3 and 4. Samples 
for hemoglobin A1C measurement will also be collected at Visit 1, 6, 7 and 8. Hematocrit will be 
assessed using local lab or Point of Care testing device.  
 
Total Estimated Blood Loss 
Maximum estimated blood loss over the study is 504 mL. 
 
 
7 
SUBJECT SAFETY, STOPPING RULES, AND STUDY EXIT 
 
7.1 
Diabetes and Safety Considerations during Clinic Visits 
Diabetes care in the Clinic Visit will be the responsibility of the Investigator and 
appropriately delegated staff. As diabetes self-management is an integral part of diabetes 
care, the Investigator may work closely with the Study subject, when appropriate, to 
determine the best approach, however the ultimate responsibility lies with the 
Investigator.  
7.1.1 Medical oversight 
There will be staff trained in emergency response, and there will be an EKG and emergency 
cart available at the site at all times.  Site-specific safety guidelines will be utilized for 
subject safety management during periods of hyperglycemia (including monitoring blood 
ketones) and hypoglycemia. Study staff (MD, DO, or NP who has experience in diabetes 
management) will also be immediately available at all times during hypoglycemia and 
hyperglycemia challenges. A nurse, nurse practitioner, or physician will be at the bedside or 
on the unit throughout the entire visit. 
7.1.2 Sensor Site 
The sensor insertion sites will be assessed (visually, as well as by palpation, and by eliciting 
Subject history) at each clinic visit, and the Subject will be instructed to call the clinic if signs 
or symptoms of irritation or infection (increased temperature, pain, redness, warmth, 
swelling, or purulence) are observed at any time.  Sensor site infections are to be treated 
with antibiotics, either topical or oral. 
 
At any time during the study if  the  study  physician  determines  that  there  is  an infection 
at  the  sensor insertion site that has not responded to treatment within 3 days, study 
procedures other than safety procedures will be stopped, and the sensor will be removed. In 
the event of an insertion site infection and sensor removal, the subject will be withdrawn 
from the study and not replaced. 
 
7.1.3 Other Considerations and Safety Assessments 
• An assessment and documentation of adverse events occurring in clinic and during 
home use will be on-going. 

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• Urine pregnancy testing (for women of childbearing potential) will be performed at the 
start of visits 1 through 8   with study exit as described in section 7.2.4 if the Subject is 
pregnant.   
• Subjects will arrive at Clinic Visits, having followed their usual diabetes care, including 
insulin dosing and food. 
• Subjects must not be afebrile in the 24 hours prior to Clinic Visits 2-8. 
• IV access is required during Clinic Visits 3 through 8. In the event of loss of IV 
access, glucose measurements may be made using Subject SMBG meter or 
alternate sampling method for subject care. Investigator may determine when 
further attempts at IV access will cease. 
• 
In order to prevent adverse effects that may occur as a result hyperglycemia challenge, 
unlimited sugar free oral fluids should be provided to subjects to prevent dehydration 
secondary to hyperglycemia. 
• “Insulin stacking” should be avoided. No bolus insulin (SQ or IV) should be 
administered less than approximately 3 hours after a previous SQ fast-acting insulin 
bolus dose or less than approximately 1 hour after a previous IV fast-acting insulin 
bolus dose (unless necessary to treat DKA, in which case, IV fast-acting bolus insulin 
may be administered less than 3 hours after a previous SQ fast-acting insulin bolus 
dose as per the protocol of the institution). 
7.1.4 Hypoglycemia 
The Subject will be asked to alert the study team anytime he or she experiences symptoms 
of hypoglycemia (i.e., shakiness, dizziness, sweating, headache, moodiness, difficulty 
concentrating, or the Subject’s usual symptoms of hypoglycemia). The symptoms will be 
confirmed by Subject SMBG Meter and/or YSI. 
 Intravenous access is to be maintained during the Clinic Visit and available for 
hypoglycemia treatment as indicated. Glucagon by injection and IV dextrose will be 
available at the site and may be used as clinically indicated.  A heating pad or heating 
chamber may be used during the session to minimize potential for occlusion or to enable 
the insertion of the port.   
YSI and/or Subject SMBG meter BG will be checked every 5 minutes until glucose >75 
mg/dl.   

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7.1.4.1 Guidelines for treatment for hypoglycemia 
During hypoglycemia challenge or monitoring period, site will follow section 5.12 
hypoglycemia challenge table. Subject safety prevails and Investigator may treat for 
hypoglycemia when clinically indicated. 
 
Subjects will be treated for hypoglycemia as appropriate according to the following table:  
 
Glucose level Glucose administration 
Safety 
<60 mg/dL 
Treat hypoglycemia as 
appropriate  using oral 
carbohydrates such as glucose 
tablets or juice (~15 g. and check 
glucose in 15 minutes minimum, 
repeat) until BG >60 mg/dL 
If subject is unable to ingest 
glucose orally, IV dextrose 
(~2-3 mL/kg D10 intravenous 
or up to 30 ml D50%) may be 
used. Glucagon will be 
available for emergency. 
60 – 75 
mg/dL 
Treat hypoglycemia as 
appropriate using oral 
carbohydrates such as glucose 
tablets or juice (~10 g. and check 
glucose in 15 minutes minimum, 
repeat) until BG >60  mg/dL 
 
• Glucose <60 mg/dL will be treated orally with fast acting carbohydrate as tolerated by 
the subject and as needed until a glucose level of ≥75 mg/dL is achieved.  
• Risk for severe hypoglycemia is defined as any of the following situations: 
o Glucose <50 mg/dL 
o The subject is unable to cooperate with oral treatment of hypoglycemia 
o The glucose is dropping at a rate that may not respond adequately to oral 
treatment 
o The subject experiences symptoms of neuroglycopenia (e.g. lethargy, 
disorientation, confusion [disordered processing of information or 
communication], or inappropriate behavior)  
o The subject experiences symptoms of severe hypoglycemia (i.e. hypoglycemic 
seizure or loss of consciousness)  

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• In the event that there is NO intravenous access and the subject is at risk for severe 
hypoglycemia (as defined above), the subject will be treated with 1 mg of glucagon 
subcutaneously or intramuscularly.  
o The drug will be reconstituted and administered per package insert/instructions.  
o Glucagon may be repeated as needed every 20 minutes to achieve glucose level 
≥75 mg/dL. Once the subject is able to consume oral treatment, the subject will be 
treated orally with fast acting carbohydrate as needed until a glucose level of ≥75 
mg/dL is achieved. Orange juice and milk will be avoided after glucagon 
administration.  
o Attempts will be made to reestablish intravenous access.  
• The accuracy (sampling) visit will be stopped if the subject experiences a hypoglycemic 
seizure or loss of consciousness and only safety procedures will be continued. The 
study physician or nurse practitioner will take control over glucose sampling decisions 
in order to stabilize the subject’s glucose between 100-300 mg/dL and determine the 
appropriate subject disposition (i.e. home or medical facility).  
7.1.5 Hyperglycemia and Blood Ketone Monitoring 
The Subject will be asked to alert the study team anytime he or she notes symptoms of 
hyperglycemia (i.e. thirst, increased urination, or other symptoms). A glucose level will be 
confirmed by YSI or Subject SMBG meter. 
 
If glucose >400 mg/dl and no symptoms and no ketones, the cause of the hyperglycemia 
will be investigated and treated as appropriate by the Investigator. Fingerstick blood 
ketones, using commercially available ketone meter will be monitored if blood glucose 
≥300 mg/dl and hourly until resolved. 
 
If blood ketones ≥ 0.6 mmol/L; subject participation in glucose challenges will be stopped 
for the day. Appropriate care will be provided, including fluids and insulin as determined by 
Investigator. Standard-of-care troubleshooting for insulin pump users will take place, 
including change of infusion set if indicated and insulin by injection if indicated. 
During hyperglycemia challenge or monitoring period, site will follow section 5.12 
hyperglycemia challenge table. Subject safety prevails and Investigator may treat for 
hyperglycemia when clinically indicated. 
7.1.5.1 Treatment Guidelines for Hyperglycemia and Ketones 
Subjects will be treated for hyperglycemia according to the following table:  

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Ketone 
BG 
 
<0.6 
0.6-1.5 
>1.5 
<300 
 
• Glucose challenge will be 
stopped 
• Ketone testing will be 
repeated hourly until 
<0.6 
• Subject will be treated 
with SQ insulin targeting 
120mg/dL using subject’s 
insulin sensitivity factor 
• Accuracy (Sampling) visit will 
be stopped, only safety 
procedures will continue 
• Ketone testing will be 
repeated hourly until <0.6 
• Subject will be treated with 
SQ insulin targeting 
120mg/dL using subject’s 
insulin sensitivity factor 
>300 
• Ketone 
testing will be 
repeated 
hourly until 
BG <300 
 
• Glucose challenge will be 
stopped 
• Ketone testing will be 
repeated hourly until 
<0.6 
• Subject will be treated 
with SQ insulin targeting 
120mg/dL using subject’s 
insulin sensitivity factor 
• Continue monitoring until 
BG <300 
• Accuracy (Sampling) visit will 
be stopped, only safety 
procedures will continue 
• Ketone testing will be 
repeated hourly until <0.6 
• Subject will be treated with 
SQ insulin targeting 
120mg/dL using subject’s 
insulin sensitivity factor 
• Continue monitoring until BG 
<300 
 
• If the subject’s glucose is >300 mg/dL or ketone level is ≥0.6 mmol/L on admission, the 
subject will be stabilized per the procedures above. The subject will continue to be 
monitored until a glucose level between 100-300 mg/dL and ketone measurement <0.6 
mmol/L has been achieved (or the subject is discharged to an appropriate medical team). 
Blood sample collecting and analysis on YSI will continue during this time. 
• Subsequently, glucose >300 mg/dL for >2 hours or glucose ≥400 mg/dL at any time will 
prompt discontinuation of the Hyperglycemia challenge. 
• Ketones will be assessed hourly while the glucose is ≥300 mg/dl or the ketone level is ≥0.6 
mmol/L.  
• If the glucose is >300 mg/dL and ketone level is <0.6 mmol/L, corrective action will be 
taken only after it has been approximately 60-120 minutes from the last subcutaneous 
insulin dose. Specifically, the subject will be asked to bolus with his/her pump or deliver by 
injection an amount of corrective insulin that will bring him/her to a target glucose of 120 
mg/dL. 

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• If the ketone level is ≥0.6 mmol/L, the cause of the elevated ketone level will be 
investigated (e.g. pump or pump site malfunction). Additional insulin may be administered 
either via insulin syringe or via a new pump site. The amount of insulin administered will 
be calculated using the subject’s insulin sensitivity factor and a target glucose of 120 
mg/dL.   
• Insulin treatment for hyperglycemia or ketones should be done using the subject’s own 
insulin. In the event that the subject’s own insulin appears to be compromised (not having 
the expected effect on the subject’s blood glucose), appropriate insulin (based on the 
subject’s normal insulin type and concentration) provided by the site may be used. 
If the ketone level is ≥1.5 mmol/L, the accuracy (sampling) visit will be stopped and the study 
MD or NP will take control of the subject's insulin dosing. The cause of the elevated ketone level 
will be investigated (e.g. pump or pump site malfunction). If the subject's home parameters are 
not felt to be working adequately due to hyperglycemia, ketonemia, or other factors (e.g. 
intercurrent illness), the study MD or NP will administer corrective insulin either via insulin 
syringe or via a new pump site using an ISF determined to be appropriate for the setting and a 
goal glucose of 120 mg/dL. The subject will continue to be monitored until a glucose level 
between 100-300 mg/dL and ketone measurement <0.6 mmol/L has been achieved (or the 
subject is discharged to an appropriate medical team). 
7.2 
Subject Stopping Rules 
7.2.1 Stopping challenges 
Glucose challenges will be stopped and subject will enter free range glucose control if: 
• 
Subject meets the challenge completion criteria: 
o Hypoglycemia challenge - approximately 120 minutes <75 mg/dL including 30 
minutes <60 mg/dL 
o Hyperglycemia challenge – approximately 120 minutes >180 mg/dL including 
60 minutes >325 mg/dL 
• 
Subject requests to end the challenge due to discomfort (desires food and/or 
insulin) 
• 
Subject ketone measurement ≥0.6 mmol/L and glucose is >300 mg/dL 
These subjects will be eligible to continue participating in challenges at future accuracy 
(sampling) visits. Blood sample collecting and analysis on YSI will continue during this time. 

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7.2.2 Stopping challenges – no reattempt 
Glucose challenges will be stopped and subject will enter free range glucose control 
if: 
• 
Subject develops significant nausea, vomiting, abdominal pain, chest pain, or 
develops ketoacidosis 
• 
The subject is unable to cooperate with oral treatment of hypoglycemia 
• 
The glucose is dropping at a rate that may not respond adequately to oral 
treatment 
• 
The subject experiences symptoms of neuroglycopenia (e.g. lethargy, 
disorientation, confusion [disordered processing of information or 
communication], or inappropriate behavior)  
Subjects may continue to participate in the study, including future accuracy (sampling) visits 
but only under observation; participation in future glucose challenges will not be allowed. 
7.2.3 Stopping accuracy (sampling) visit 
During accuracy (sampling) visits, study procedures other than those required for subject 
safety will be stopped for that day if any of the following occur: 
• The subject had a serious adverse event that is deemed either related to study or 
in the investigator’s opinion requires stopping 
• 
Medical intervention is required to treat severe hypoglycemia (seizure, 
unconsciousness, etc.) 
• Adequate intravenous access cannot be maintained 
• The YSI and back-up YSI, (if available), stop functioning and neither can be re-
established within 2 hours. 
• Subject requests to stop 
• Investigator determines it is in Subject’s best interest to stop the accuracy (sampling) visit 
7.2.4  Subject withdrawal 
Subjects will be withdrawn from the study if: 
• Subject is noted to be pregnant at any Visit.  
• The subject may withdraw if he/she had a serious adverse event that is 
deemed either related to study device or procedures.  

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• 
The subject experiences symptoms of severe hypoglycemia (i.e. hypoglycemic 
seizure or loss of consciousness)  
• 
Subject experiences DKA (related to the use of the study device) during home use 
• Subject voluntarily withdraws from study 
• There  is  an infection at  the  sensor insertion site that has not responded to 
treatment within 3 days 
• Subject needs an MRI and Sensor is removed and not replaced. 
• Investigator determines it is in Subject’s best interest to withdraw. 
• 
Subject is lost to follow-up 
• 
Subject dies 
7.2.5 Study Exit 
A Subject’s participation is considered complete after Visit 9 (or Follow-up Visit). A Subject 
may choose to withdraw at any time without adverse effect on their care. The subject will 
continue with their medical follow-up, according to standard-of- care. The reason for study 
withdrawal will be documented. 
 
In the event that a subject withdraws from the investigation and is lost to follow-up, the 
Investigator will make all reasonable efforts to locate a Subject and encourage Subject to 
return for Sensor removal. If a subject is lost to follow-up, three separate telephone calls 
should be made to attempt to schedule a follow-up visit or obtain follow-up information. 
All attempts and contacts should be documented in the source documents. The subject’s 
Primary Care Physician may also be contacted as stated in the Informed Consent Form.  If 
the Subject does not respond to the three telephone calls, then the Investigator will send a 
certified letter to the Subject. The Subject will be considered lost to follow-up if this 
communication is unsuccessful.   
7.2.6 Replacement of Subjects 
Subjects who exit the study prematurely may not re-enter the study, and will not be replaced. 
 
7.3 
Study Stopping Rules 
Senseonics may choose to suspend or prematurely terminate the investigation for the 
following reasons: 
• 
Subject safety issue 
• Production limitation 

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• Administrative decision 
 
The Medical Monitor will review adverse events on a scheduled periodic basis as outlined 
in Section 13.13. In the case of device-related serious adverse events, the Medical 
Monitor will consult with the Sponsor and Principal Investigator if appropriate to ensure 
that the necessary steps are taken to protect the safety and well- being of the Subjects. 
 
 The study may be suspended for subject safety reasons.   If two or more subjects are 
stopped (subject withdrawal per section 7.2.4) for the same adverse event related to 
device, and/or insertion/removal procedure, then the associated portion of the study 
should be suspended to allow for an investigation. For example, if two subjects are stopped 
due to infections that do not respond to treatment within three days, new sensor 
insertions should be suspended while the root cause is investigated. 
 
In the event that that study is stopped, the Investigator will promptly inform the Subjects 
and ensure appropriate therapy and follow-up, including Sensor removal.  Additionally the 
investigator will promptly inform the IRB and provide a detailed written explanation. The 
pertinent regulatory authorities will be informed according to local regulations. 
 
7.4 
Termination of Investigator or Investigational Site 
Senseonics reserves the right to terminate an investigator/investigational site for any of the 
following reasons, which are considered major deviations: 
• 
Failure to secure subject informed consent including protection of personal data 
prior to enrollment 
• 
Failure to report unanticipated adverse device effects and serious adverse events to 
Senseonics and to the IRB/ EC within its required reporting time after learning of the 
event 
• 
Repeated investigational plan deviations 
• 
Loss of or unaccounted for investigational product inventory. 
 
 
8 
RISK AND BENEFIT ANALYSIS 
 
8.1 
Potential Benefits 
There will be no direct benefit to the subjects participating in the investigation other than 
the knowledge that they are contributing to the overall advancement of medical and 
scientific knowledge that may benefit future subjects with similar conditions. The CGM 
data collected will not be used for any clinical decisions or care. 

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8.2 
Potential Risks 
The Senseonics CGM System is investigational and is therefore not considered to be a 
medical standard. To evaluate the Senseonics CGM system, blood draws for glucose 
measurements will be performed more frequently than in daily routine. In addition to use of 
the System, hyperglycemia and hypoglycemia challenges may be performed exclusively for 
study purposes. 
8.2.1 Anticipated Adverse Effects 
The following adverse effects could occur in association with insertion, removal, and/or use 
of the Senseonics CGM System Sensor and/or Transmitter: 
• Infection, local or systemic, possibly resulting in sensor removal 
• Excessive bleeding during insertion or removal 
• Bruising or swelling 
• Poor wound healing after insertion or removal 
• Keloid and/or scar formation 
• Excessive or prolonged pain or discomfort at the Sensor site 
• Nerve damage causing tingling, numbness, pain or weakness 
• Uncomfortable heating 
• Burn 
• Electrostatic shock 
• Skin irritation and/or redness 
• Itch 
• Discoloration of skin 
• Hematoma formation 
• Device migration 
• Skin erosion 
• Allergic reaction to the device components, local anesthetic, or other medication or 
materials used in the procedure 
• Anxiety and/or nervousness and/or lack of sleep 
• Device fragments or particulate matter remaining in the body 
• Failure to retrieve device or device left behind 
• Difficulty in removing device that may require surgery 
• Device malfunctions of the Sensor and/or Transmitter with possible need to remove 
and/or replace the Sensor and/or Transmitter 
• Burning sensation or pain. 
• Elevated blood pressure 
• Water retention in the tissue, swelling or edema 
• Airway spasms 

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• Shortness of breath 
• Circulatory disorders 
• Confusion 
• Disorientation 
• Increased or decreased sensitivity to touch or pain 
• Metallic taste 
• Sleepiness 
• Visual disturbances and/or blurred vision 
• Tinnitus 
• It is possible that the local anesthetic could cause a reaction other than listed or 
previously seen. 
• Fluid/electrolyte disturbances such as fluid retention 
• Muscle weakness 
• Osteoporosis 
• Peptic ulcer 
• Pancreatitis 
• Ulcerative esophagitis 
• Impaired wound healing 
• Headache 
• Psychic disturbances and mood swings 
• Convulsions 
• Glaucoma 
• Weight gain 
• Nausea and/or vomiting 
• Malaise 
• Irritability 
• Insomnia 
• Heartburn 
• Hyperglycemia 
• Ketosis 
• Headaches 
• Dizziness, lightheadedness, and/or fainting 
• It is possible that the use of the Senseonics CGM system could cause a reaction other than 
listed or previously seen. 
• It has not been determined whether the risks usually associated with injectable 
dexamethasone apply to the use of dexamethasone elution ring, a highly localized, 
controlled-release device. 
• The dexamethasone ring could cause other adverse events not listed or previously seen. 

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• Other adverse events typically related to diabetes treatment and diabetes are unknown 
 
8.2.2 Residual Risks Associated with the Investigational Device 
Components of the Senseonics CGM System are manufactured under the Quality System 
provisions of ISO 13485:2003. 
Risk analysis has been performed and adequate control put in place as prescribed in 
relevant provisions of IEC 62304, ISO 14971, and IEC 60601-1, in accordance with the 
requirements of ISO 13485:2003. Residual risks associated with the device included risks in 
the categories of electromagnetic and thermal energy, biocompatibility, biologic, chemical 
and mechanical factors, and user-related error.  All identified risks have been reduced as far 
as possible using various control methods including software revision and re-validation, 
hardware design modification, packaging and sterilization process validation and labeling 
revision. The calculated residual risks were determined to be acceptable for conduct of 
this clinical investigation. 
8.2.3 Risks Associated with Participation in the Clinical Investigation 
This clinical investigation involves subjects with diabetes mellitus. These subjects may 
experience hyperglycemia and hypoglycemia as a consequence of their existing condition 
and medical management (e.g. insulin administration). For this study, hyperglycemia and 
hypoglycemia will not be reported as adverse events unless meeting criteria of a Serious 
Adverse Event. Episodes of hyperglycemia and hypoglycemia as documented by the 
Subject SMBG Meter will be reported in an extra listing separate from the AE listings. 
Should a known side effect(s) occur to administered medication(s) used in the intervention, 
such effects will be reported as part of the adverse event description and will not be 
considered a separate adverse event. 
The amount of blood drawn for in-clinic testing during   the study is below the acceptable 
limits of blood donation of approximately 475 mL; hence it does not pose any additional 
unacceptable risk to the subjects. 
This clinical investigation involves the following procedures that present risk:  placement of 
an intravenous catheter, frequent blood sampling, and conduct of hyperglycemia and 
hypoglycemia challenges at the clinic visits. In addition, Subjects in this study may use an 
insulin pump or syringes to administer subcutaneous insulin. 
 
The following risks are potentially associated with such procedures: 
 

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• 
Routine administration of insulin may cause hematoma, redness, swelling and itch at 
the injection site, skin rash, itch, sweating, gastro-intestinal complaints, edema, 
difficulty breathing, palpitations and drop in blood pressure, and even death. 
• 
Hypoglycemic symptoms requiring medical intervention which may include 
seizures, neuroglycopenia, coma and even death (including occurrence 
during home use) 
• 
Insulin administration leading to hypoglycemia include: cold sweating, cool and pale 
skin, fatigue, nervousness, shakiness, anxiety, weakness, confusion, feeling of 
numbness, hunger, impairment of vision, problems with concentration, headache, 
nausea, palpitations, coma, or death. 
• 
Hyperglycemia and diabetic ketoacidosis requiring medical intervention which may 
include potential complications such as nausea, vomiting, abdominal pain, 
dehydration, difficulties with breathing, confusion, bad breath, low blood pressure, 
coma, kidney failure, cardiac arrhythmia, myocardial infarction, cerebral edema, 
rhabdomyolysis and even death (including occurrence during home use). 
• 
Excessive pain during insertion of the IV catheter 
• 
Multiple sticks due to IV placement 
• 
IV placement failure 
• 
Restricted mobility 
• 
Fainting, dizziness, lightheadedness or low blood pressure in response to blood sampling 
• 
Bleeding during catheter insertion or infusion pump infusion set change 
• 
Bruise formation at catheter site or due to infusion pump use 
• 
Fluid overload due to saline flushes of IV catheter 
• 
Skin redness or scarring due to infusion pump use 
• 
Temporary muscle or nerve irritability, arrhythmia or death due to electrolyte disturbance 
• 
Tissue damage (burn) due to heating devices 
• 
Severe gastro-intestinal distress 
• 
Difficulty breathing 
• 
Cardiovascular symptoms 
• 
Nerve damage 
• 
Rash 
• 
Pain 
• 
Infection, local or systemic 
• 
Blood clots, which may cause inflammation, swelling and pain 
• 
Circulatory disorders, including but not limited to low blood pressure 
• 
Skin irritation or pruritus due to medical adhesive (electrodes, tapes, etc.) 
• 
Infection, inflammation or phlebitis at IV insertion sites or infusion pump infusion set sites 
• 
Edema at the insertion site 

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• 
Erythema at the insertion site 
• 
Allergic reaction 
• 
Excessive pain or burning sensation associated with injections 
• 
Headache 
• 
Vasovagal response or fainting 
• 
Anemia due to blood sampling 
• 
Muscle soreness or extremity injury from exercise including weight lifting 
 
Subject may have an X-ray or ultrasound of the sensor site. X-rays may cause damage to 
cells in the body, which in turn may increase the risk of developing cancer. This increase in 
risk associated with each X-ray procedure is extremely low but does slowly increase with 
the increasing number of X-rays tests you have. 
 
Even though there are no known risks of ultrasound imaging, it can produce effects on the 
body. When ultrasound enters the body, it heats the tissues slightly. In some cases, it can 
also produce small pockets of gas in body fluids or tissues (cavitation). The long-term 
effects of tissue heating and cavitation are not known. 
8.2.4 Possible Interactions with Concomitant Medical Treatments 
Subjects participating in the investigation will be provided with a card advising of the 
contraindication of magnetic resonance imaging (MRI), and providing contact information 
of the investigational site. 
Subjects must not undergo MRI while the Sensor is inserted or the Transmitter is in place. 
Both are incompatible with MRI procedures. Serious injury such as internal tissue burn 
(from the Sensor overheating) or topical skin burn (from the Transmitter overheating) may 
occur during an MRI and subsequent localized infection may develop as a result of the 
Sensor overheating. 
If an MRI is required for subject care, the Sensor should be removed and the Subject will be 
withdrawn from the study, according to study stopping rules. 
 
In the event of a situation where MRI is required and it is not possible to remove the Sensor, 
Subject is advised to have medical staff contact the Sponsor. 
8.2.5 Dexamethasone 
As it has not been determined whether the risks usually associated with injectable 
dexamethasone apply to the use of dexamethasone elution ring, a highly localized, 
controlled-release device, routine blood dexamethasone measurements have been 
incorporated into the study design. 

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8.2.6 Electrostatic Shock 
The external device (Transmitter) has been tested and passed the Electrostatic Discharge 
(ESD) test according to IEC 61000-4-2:2008 air and contact immunity test levels in 
accordance with IEC 60601-1-2:2014 EMC collateral standard. No known damage to the 
external device or to the overall CGM system has been observed as documented in the 
EMC report. 
 
8.3 
Efforts to Minimize Risk 
This investigation will be conducted by investigators who are qualified by training and 
experience in the treatment of diabetes mellitus and specifically in the execution of 
hyperglycemia and hypoglycemia challenges. In the event of a clinical emergency, detailed 
safety plans will be in place at each clinical site for monitoring and the management of 
clinically significant hypoglycemia and hyperglycemia. A full resuscitation cart with 
defibrillator, and staff trained in the care of diabetes and cardiac emergencies will be 
present at site. A nurse, nurse practitioner or physician will be present at the bedside or 
unit at all times. A study physician or nurse practitioner will be present during the 
hypoglycemia and hyperglycemia challenge times. 
In addition, adequate measures including eligibility criteria limitations, subject screening 
and pre- visit assessment of the subject’s diabetes status have been incorporated into the 
clinical investigation with the intention of minimizing such risks. 
Investigators will be trained in the technique for Sensor insertion and removal. Investigators 
will examine the insertion site during each in-clinic visit and document any suspected 
adverse event. Subjects will be instructed to contact the investigator immediately upon any 
sign of significant irritation or discomfort or evidence of infection as described previously. 
In addition, an independent medical monitor will review safety related aspects of the 
investigation including review of serious adverse events and unanticipated adverse device 
effects. 
 
Furthermore, potential risks associated with participation in this investigation will be 
minimized and managed in accordance with 21 CFR Part 812, ISO 14155, regulations by local 
regulatory authorities and requirements of the approving Investigational Review Boards and 
Ethics Committee(s). 
 
8.4 
Risk to Benefit Ratio 
The Sponsor believes that any potential risk presented by this investigation has been 
minimized and that adequate testing, safeguards, and safety monitoring have been 
incorporated into the investigation to further minimize and mitigate the risks. 

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The Sponsor believes that the value of the knowledge to be gained by conducting this 
clinical investigation to demonstrate the safety and accuracy of the Senseonics CGM 
System outweighs the potential risks posed to participating subjects. 
All potential study Subjects will sign an informed consent form and conduct a discussion 
with delegated investigative personnel concerning the risks and benefits of participating in 
the clinical trial. 
 
9 
ADVERSE EVENTS 
 
The following are definitions and requirements for adverse event monitoring and reporting. 
The definitions and requirements of local regulations will be followed if different from below. 
The name and telephone number of the individual for the Site to contact regarding safety 
issues is listed in the General Information and Contacts section in the front of the protocol. 
Subjects will contact the Investigator with any questions or concerns. The Investigator will 
contact Senseonics with questions regarding recording and reporting of adverse events. 
 
9.1 
Adverse Event Definitions 
Adverse Event (AE) is defined as any untoward medical occurrence, unintended disease or 
injury, or untoward clinical signs (including abnormal laboratory findings) in subjects, users or 
other persons, whether or not related to the investigational medical device.   
NOTE 1 This definition includes events related to the investigational medical device or 
the comparator. 
NOTE 2 This definition includes events related to the procedures involved. 
NOTE 3 For users or other persons, this definition is restricted to events related to 
investigational medical devices. 
 
Serious Adverse Event (SAE) is defined as an adverse event that: 
 
• Leads to death; 
• Leads to a serious deterioration in the health of the Subject that either: 
o Results in life-threatening illness or injury; or 
o Results in a permanent impairment of a body structure or a body function; or 
o Requires inpatient or prolonged hospitalization; or 
o Results in medical or surgical intervention to prevent life-threatening illness or injury 
or permanent impairment to a body structure or a body function; 
• Led to fetal distress, fetal death or congenital abnormality or birth defect; 
• Significant medical event. 
 

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NOTE: Planned hospitalization for a pre-existing condition, or a procedure required by the 
CIP, without serious deterioration in health, is not considered a serious adverse event. 
 
Anticipated adverse events are AEs that have been identified as possible adverse events 
related to the investigational device or procedure.  
 
Unanticipated adverse device effects (UADEs) are defined as 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 study subjects. 
 
Severity 
Mild: Awareness of a sign or symptom that does not interfere with the Subject’s usual 
activity or is transient, resolves without treatment and with no sequelae 
Moderate:  Interferes with the Subject’s usual activity and/or requires symptomatic 
treatment 
Severe: Symptom(s) causing severe discomfort and significant impact on the Subject’s usual 
activities and/or requires treatment 
 
Causality: The causal relationship should be determined with respect to the investigational 
device, the insertion or removal procedure, or other study-related procedures. 
 
None:  The event is not associated with the device or procedure. There is no relation 
between the event and the device or procedure. 
Possibly Related: The temporal sequence between the device or procedure and the event is 
such that the relationship is not unlikely or there is no contradicting evidence that can 
reasonably explain the Subject’s condition. There is a possibility of any relation between 
the event and the device or procedure. 
Related: The temporal sequence is relevant or the event abates upon device application 
completion/removal or the event cannot be reasonably explained by the patient’s 
condition or comorbidities. The event is related or most likely associated with the device or 
procedure. 
Unknown: There is no evidence or relevant data available to assess the relationship 
between the event and the device or procedure. 
 
 
 

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9.2 
Monitoring of Adverse Events 
Adverse events (AEs) may be volunteered by Subjects, elicited by Investigator or others, or 
observed.  All AEs will be assessed by the Investigator who will determine whether or not 
the event is related to the device, and/or insertion or removal procedure or other study-
related procedure. The Investigator will determine whether or not the event meets the 
serious criteria. If it is determined that an AE has occurred, the Investigator should obtain all 
the information required to complete the reporting process, including source 
documentation. 
 
9.3 
Adverse Event Reporting 
All adverse events (AEs) will be reported by the Investigator and reviewed by the Sponsor in 
compliance with applicable regulations. Site will follow local IRB reporting requirements for 
reporting to IRB. 
All SAEs must be reported to Sponsor as soon as possible but in no event later than 48 hours 
after learning of the event. Include Study ID, Study Site, Adverse Event, causal relationship 
to device and procedure (insertion/removal/other study procedure), seriousness, 
expectedness, and provide source documentation as soon as available. The AE form of the 
CRF must be completed within 3 working days of awareness for all SAEs. 
All UADEs must be reported to the Sponsor and to the reviewing IRB as soon as possible, but 
in no event later than 48 hours after  the Investigator first learns of the event (21 CFR 
812.150(a)(1)). The AE form of the CRF must be completed as soon as possible but no later 
than 3 working days for all UADEs.  
All adverse events classified as possibly related or related to the device or procedure will be 
reported to Senseonics as soon as possible but no later than 3 days of learning of events. 
9.3.1 AE Reporting Period 
Adverse events are reported from enrollment until study participation has ended. Adverse 
events will be followed until resolution, AE has stabilized, or the study has been 
completed. 
9.3.2 Pre-existing Medical Conditions 
Pre-existing medical conditions or symptoms reported prior to enrollment will not be 
recorded as an AE. In the event there is a change in the pre-existing medical condition or 
symptoms due to the device or study-related procedure, than an AE must be recorded. 

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9.3.3 Protocol-Specific Reporting Information 
For the purpose of this protocol, mild (i.e., clinically non-significant) hypoglycemia and 
hyperglycemia symptoms or blood glucose values out of the normal range will not be 
reported as adverse events unless determined to meet the criteria of a Serious Adverse 
Event. 
 
9.4 
Device Deficiencies 
All device deficiencies related to the identity, quality, durability, reliability, safety, or 
performance of an investigational medical device shall be documented throughout the 
clinical investigation and appropriately managed by the Sponsor. Device deficiencies include 
malfunctions, use errors, and inadequate labeling. 
 
 
10 SOURCE DOCUMENTATION, CASE REPORT FORMS AND DATA MANAGEMENT 
 
Data in this study will be collected on Case Report Forms (electronic or paper) as well as 
electronic file transfers. 
 
10.1 Source Documents and Case Report Forms 
The investigator or his/her designee at each site is responsible for recording investigation-
related data onto the CRFs and maintain source documentation supporting the data. Good 
Clinical Practice in the documentation on source documents and CRFs will be followed. For 
source documentation or if papers CRFs are used, the data must be legibly written in ink. If 
changes are required, a single line is to be drawn through the incorrect information, the 
correct information written in and the change initialed and dated by the individual making 
the change. The reason for correction may be noted, unless obvious. Pencil, correction 
fluid or correction tape must not be used and incorrect information must not be obscured 
(scribbled-out). 
The investigator must review, sign, and date the CRFs as indicated on the form or 
electronically; these responsibilities cannot be delegated to another person. It is the 
investigator’s responsibility to comply with regulatory requirements including, but not 
limited to, the maintenance of accurate, complete and current records relating to the CRFs. 
Data clarification forms (DCFs) may be generated by Senseonics (or designee) or by the 
monitor during a monitoring visit. DCFs are treated as CRFs and are completed and signed 
by the investigator or designee. 
The Sponsor (or their designee) will review the data against the original source documents 
and ensure any noted discrepancies are resolved by the investigational site. Subject data 

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will be compared to information originally recorded on source documents related to the 
trial (i.e. professional notes, laboratory reports, investigation-specific worksheets, etc.). 
Investigation-related information collected on CRFs will be entered into a secure database. 
The database design and installation will be validated prior to use. 
Validation techniques used by Senseonics are consistent with applicable regulations and 
guidelines. Each database must pass a series of standard tests that demonstrate the usability 
and correctness of the database system to approved specifications. The test process 
generates detailed test result logs, which are provided as part of the database 
documentation. 
The details of data review, database cleaning and data querying are described in a Data 
Quality a n d  Management Plan (DQMP). This plan is updated throughout the investigation 
as amended data management requirements and investigation-specific data conventions 
are determined. 
A comprehensive EDC User Guideline will be developed for participating investigational 
sites describing general instructions on CRF completion; this guideline also includes 
investigation- specific data entry, and query management instructions. 
Data entered by investigational sites will be reviewed by the Sponsor or their designee 
on an ongoing basis to ensure adequate query resolution and identify and query 
adverse events, protocol deviations, and any other ambiguous data points. 
 
10.2 Glucose Measurement Data Flow Process 
10.2.1 Data Logging 
The Transmitter is a rechargeable, external device worn over the Sensor insertion site that 
supplies power to the Sensor. The Transmitter periodically (usually every 5 minutes) reads 
sensor data and calculates sensor glucose and trends. The information from the 
Transmitter is then transmitted for display to a handheld device (e.g. Smartphone) via 
Bluetooth Low Energy with AES-CCM encryption. At any one time, the Transmitter contains 
all of the data collected since last erasure, extending back in time to the limit of its 
capacity. Each Sensor reading is recorded with a timestamp. Successive uploads from a 
subject’s assigned Transmitter can be assembled into a cumulative time profile, using these 
timestamps. 
10.2.2 Data Retrieval 
Data from Subject Assigned Transmitters will be collected at clinic visits. The data will be 
downloaded by a data communication device running Senseonics’ custom software 

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application and saved to a file. The file will be uploaded to a 21CFR11 compliant record, 
utilizing a 21CFR11- compliant third party software application. 
The Senseonics’ software application will identify the Sensor serial number and ask the user 
to enter the site ID, subject ID and visit number. The file name will include these identifiers 
as well as the download date and time. Transmitter data will also be uploaded to a data 
management system to monitor calibration compliance.   
Incomplete or missing data downloads that cannot be used in the analysis or cannot be 
made available at a future visit would be considered missing data for the purpose of 
analysis for the corresponding time interval. 
10.2.3  Reference Glucose Analyzer Data 
Plasma glucose data will be recorded by a YSI Analyzer and recorded on Source Document 
Forms. This data will be transferred to a 21CFR11-compliant electronic record system. 
Paper strip records and/or electronic records collected from the YSI Reference Glucose 
Analyzer will be retained according to GCP.  Printouts should be labeled, including a 
patient identifier, sample number, and operator initials, and either photocopied or 
scanned. 
10.2.4 Blood Glucose Meter Data 
Data from the study Subject SMBG Meters will be uploaded at clinic visits and electronically 
transferred to a 21CFR11-compliant electronic record system.   
Incomplete data downloads that cannot be used in the analysis or cannot be made 
available at a future download would be considered missing data for the purpose of 
analysis for the corresponding time interval. 
During and/or at the conclusion of the investigation, original data from the laptop at the 
clinical site will be transferred to a 21CFR11-compliant electronic record system. The 
clinical site will be provided a master CD/USB of the electronic data to meet record 
retention requirements. 
 
 
11 STATISTICAL METHODS 
 
11.1 Statistical Analysis Overview 
11.1.1 General Considerations 
The statistical analysis of the data is  focused on assessing performance via downloads and 
data from the clinic including the Fingerstick Blood Glucose Meter Data (Subject SMBG), the 
YSI Reference Glucose Data, the Senseonics CGM System Data, and other manual entries ( 

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e.g. Implant Time , Subject Number ). Descriptive statistics will be used to summarize all 
subject Baseline and outcome data collected during the study.  Continuous variables will be 
summarized using means, standard deviations, and ranges.  Categorical variables will be 
summarized in frequency distributions. 
 
Statistical analyses will be performed by validated software (e.g., MATLAB and SAS® 9.4).  
Adequate source document verification and/or audit activities will be utilized to assess the 
validity of investigation conclusions.  Copies of databases used to prepare clinical report 
summaries will be archived to enable any statistical analyses performed to be replicated. 
11.1.2 Randomization and Data Pooling across sites 
Subjects will not be randomized.  Subjects will be selected consecutively (i.e., selecting every 
subject in the order they present at the site) among those who meet the inclusion/exclusion 
criteria.  All subjects will receive sensors and transmitters.  The primary effectiveness 
endpoint (MARD) will be analyzed with data pooling across sites.  Site effects will be 
examined, but only descriptively.  
11.1.3 Sensor Evaluation Period 
The Senseonics CGM System performance will be evaluated in the period after insertion.  
The Transmitter will assess the Sensor’s signal sensitivity in real time for any premature 
failure independent of the expected lifetime based on time from insertion.  If the 
measurement of potential degraded response of the Sensor optical system signal drops 
below a pre-defined percent of its original value and/or systemic patterns in Sensor accuracy 
to entered calibration points drops below a pre-defined threshold, then the device has 
reached it end of life (sensor retirement) and will no longer provide glucose readings.  This 
end of life determination marks the end of the accuracy evaluation period for this Sensor.  
The distribution of times between Sensor insertion and end of life or completion of 
scheduled study visits, whichever occurs first will be summarized. 
11.1.4 Expected Paired Points by Range* 
The expected number of paired YSI/sensor points by YSI glucose range are as follows: 
 
Each Day 1, 7, 14 
16 Hr. Session 
Each Day 30,60,90 
12.5 Hr. Session 
Total 
YSI range 
40-60 mg/dL 
166 
106 
815 
61-80 mg/dL 
446 
285 
2194 
80-120 mg/dL 
1128 
722 
5550 
121-160 mg/dL 
1078 
690 
5303 
160-200 mg/dL 
712 
456 
3505 
201-250 mg/dL 
620 
397 
3052 
251-300 mg/dL 
290 
186 
1426 

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301-350 mg/dL 
127 
81 
623 
350-400 mg/dL 
65 
42 
319 
 
 
Total paired 
points 
22786 
*Estimates based on 66 sensors.  Number of YSI values in each range will be 
approximately half the number of paired points.  
 
11.1.5 Evaluable Data for Analysis 
All data will be evaluable for the study safety and effectiveness analysis. 
11.1.6 Analysis Populations 
  
Effectiveness Analysis population: The effectiveness analysis and exploratory effectiveness 
endpoints will be based on all data from all subjects in this investigation with at least one 
paired glucose reading (one Sensor with one reference glucose). The Senseonics CGM 
System and reference readings are compared by pairing each reference reading with the first 
Sensor reading that occurred up to 5 minutes after sample acquisition.   
  
Safety Analysis Population: Safety analysis will be based on all subjects that undergo the 
sensor insertion in this investigation. 
 
Dexamethasone Analysis Population: The approximately 6 subjects with Sensor’s inserted 
will constitute the dexamethasone analysis population to determine if and when a peak 
dexamethasone level occurs.  Subsequent to determining if and when a peak occurs, all 
subjects with Sensor’s inserted will constitute the complete dexamethasone analysis 
population. 
11.1.7 Dexamethasone Analysis 
The peak dexamethasone and the timing that the peak dexamethasone occurs will be 
analyzed descriptively in the subset of approximately 6 subjects.  Subsequent analysis of the 
dexamethasone levels in all subjects will be analyzed descriptively. 
11.1.8 Interim Analysis 
A planned interim analysis will be performed after all the subjects have completed Visit 6 
(day 30 accuracy visit).  Only descriptive statistics will be performed.  This interim analysis 
does not feature any stopping rules and has no impact on the collection of the complete 
follow-up data through 90 days of Sensor use. 
11.1.9 Subject Accountability 
A Subject Accountability flow diagram will account for all subjects from informed consent 
through end of study and includes any early explants or withdrawals (Figure 1 in APPENDIX 
1).   

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11.1.10 
Study Demographics Analysis  
Descriptive statistics will be provided for demographic variables and other baseline 
characteristics, such as age, gender, race, BMI, diabetes type, insulin therapy, history of 
ketoacidosis, and history of hypoglycemia.   
11.1.11 
Tabulation of Investigational Device Deficiencies  
11.1.11.1 
Transmitter Deficiencies 
A tabulation of all reported transmitter device deficiencies will be presented (Table 1 
in APPENDIX 1). 
11.1.11.2 
Sensor Deficiencies 
A tabulation of all reported sensor device deficiencies will be presented (Table 2 in 
APPENDIX 1). 
 
11.2 Safety Endpoints 
The safety endpoint is the incidence of device-related or insertion/removal procedure-related 
serious adverse events (SAEs) in the clinic and during home use through 90 days post-insertion.     
 
An Adverse Event is considered ‘related’ if the relatedness is categorized as ‘possibly related’, 
or ‘related’. The assessment of seriousness and relatedness made by the Medical Monitor 
will be used for analysis.  The numbers of SAEs and the percentage of patients with SAEs will 
be reported for each SAE type that is observed, identified as device-related, procedure-
related or unrelated to the study (Table 3 in APPENDIX 1).   The count and proportion of 
patients experiencing at least one device-related or procedure-related SAE will be presented. 
No inferential statistical analysis will be performed. 
 
Other safety endpoints include: 
• Incidence of insertion/removal procedure or device-related adverse events in the clinic 
and during home use. 
• Incidence of all adverse events in the clinic and during home use. 
• Incidence of hospitalizations due to hypoglycemia, hyperglycemia or ketoacidosis 
occurring during home use. 
• Incidence of reported hypoglycemic and hyperglycemic events occurring during home use. 
 
For each of the adverse event (AE or SAE) categories above, the numbers of AEs and the 
percentage of patients with AEs will be reported for each AE type that is observed and be 
stratified by the target age enrollment categories (Tables 4A-4E in APPENDIX 1).   A listing 
(Table 5 in APPENDIX 1) will be prepared that identifies each patient with a reported AE or SAE, 
and relevant information including date of onset, severity level, seriousness, relatedness to the 
device or procedure, classification as anticipated or unanticipated, corrective action(s) taken, 
and resolution status (resolved or ongoing). 

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11.3 Effectiveness Endpoints 
11.3.1 Summary 
The effectiveness endpoint will be the mean absolute relative difference (MARD), calculated 
for all paired Sensor and reference measurements through 90 days post-insertion.  For the 
planned interim analysis, MARD will be based on the first 30 days post-insertion data. 
11.3.2 Effectiveness Endpoint 
11.3.2.1 Effectiveness Endpoint: Criteria 
The effectiveness objective is to descriptively document the distribution of absolute 
relative difference across all evaluable subjects and to estimate the MARD. The MARD will 
be estimated initially when all the subjects complete 30 days of Sensor use for the interim 
analysis, followed by the MARD based on all the follow-up data through 90 days of Sensor 
use.   Descriptive statistics will be provided for the MARD.  There is no hypothesis to be 
tested.  No inferential statistical analysis will be performed. 
 
The effectiveness endpoint is the mean absolute relative difference (MARD), defined as the 
average of absolute difference of paired Senseonics CGM System and reference glucose 
readings divided by the reference glucose reading (reference) for all reference glucose 
values, that is:   
 
𝐌𝐌𝐌𝐌𝐌𝐌𝐌𝐌= ቀቀ∑
|  (𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆)𝐒𝐒𝐒𝐒𝐒𝐒𝐒𝐒𝐒𝐒𝐒𝐒 –(𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆)𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑 |
(𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆𝐆)𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑𝐑
ቁ    𝐧𝐧
⁄
ቁ × 𝟏𝟏𝟏𝟏𝟏𝟏%, 
 
Where, n is the total number of CGM and reference glucose pairs during the evaluation 
period, that is, after 30 days of Sensor use for the interim analysis, and after 90 days of use 
for the final analysis.    
11.3.2.2 Sample Size and Power Calculation 
This study does not feature any inferential statistics.  The sample size for the study was not 
determined based on a power calculation.  Instead, the sample size of 36 subjects with 
sensors inserted was selected based on the objectives of the study and was mutually 
agreed upon between the Sponsor and the FDA. 
11.3.2.3 Other Exploratory Effectiveness Measures 
Other exploratory effectiveness measures are discussed in this section.   Only descriptive 
statistics will be provided for these exploratory outcomes.   
11.3.2.3.1 Mean Absolute Difference (MAD) between sensor and reference measurements  
 
MAD =        ቀ෍ | (Glucose)SENSOR – (Glucose)REFERENCE |ቁ    n
ൗ
 

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11.3.2.3.2 Mean Relative Difference (RD) between sensor and reference measurements  
 
Mean RD = ൬൬෍ (Glucose)SENSOR – (Glucose)REFERENCE
(Glucose)REFERENCE
൰    n
ൗ
൰ × 100% 
11.3.2.3.3 Median Absolute Relative Difference (ARD) between sensor and reference 
measurements  
Median ARD = Median ((
  | Glucose)SENSOR –(Glucose)REFERENCE | 
(Glucose)REFERENCE
)i) x 100%,  i = 1, 2, …, n 
11.3.2.3.4 Median Absolute Difference between sensor and reference measurements 
 
Median AD = Median ( | (Glucose)SENSOR – (Glucose)REFERENCE |𝑖𝑖), i = 1,2, … , n 
11.3.2.3.5 Median Relative Difference between sensor and reference measurements  
 
Median RD =  Median ((
 (Glucose)SENSOR –(Glucose)REFERENCE
(Glucose)REFERENCE
)𝑖𝑖) × 100%, i = 1, 2, …, n 
11.3.2.3.6 System agreement with reference 
The Agreement of the CGM System to reference measurements will be assessed by 
looking at proportions of all differences { (Glucose)SENSOR – (Glucose)REFERENCE } in 
intervals of [0 – 15%], [0 – 20%], [0-30%], and [0-40%). For readings less than or equal to 
80 mg/dL, the absolute difference in mg/dL between the two glucose results will be 
calculated. For values greater than 80 mg/dL, the absolute percent difference (%) from 
the reference values will be calculated.  
11.3.2.4 Effectiveness measures in full glucose range and different glycemic regions  
Mean/median absolute relative difference, mean/median relative difference, 
mean/median absolute different when reference YSI≤80 mg/dl, and Agreement between 
CGM and YSI glucose will be stratified based on YSI glucose ranges. Similar stratification 
based on CGM glucose will also be performed. (Tables 6A-6D in APPENDIX 1). 
11.3.2.5 Concurrence of System Readings and YSI values 
Tables for concurrence of system and YSI values will be tabulated (Tables 7A and 7B in 
APPENDIX 1).  
11.3.2.6 Stability of the system throughout sensor life 
For the full 90 day duration of the study, performance of the system overtime will be 
assessed by visit number (Table 8 in APPENDIX 1).   
11.3.2.7 Sensor precision analysis 
Sensor precision will be evaluated by paired absolute relative difference (PARD) and 
percent coefficient of variation (PCV). PARD is the absolute value of the Primary Sensor 
reading minus the paired Secondary Sensor reading divided by the average of the two 

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Sensor readings. PCV is the standard deviation of the two paired Sensor readings divided by 
the average of the two paired Sensor readings. The mean values of PARD and PCV will be 
tabulated (Table 9 in APPENDIX 1). 
 
PARD = ൬൬෍ |Glucose)SENSOR 1 – (Glucose)SENSOR 2 |
( Mean Glucose)SENSOR 1 and 2
൰    n
ൗ
൰ × 100% 
 
 
PCV = ቀቀ∑SD of (Glucose)SENSOR 1 and (Glucose)SENSOR 2 
( Mean Glucose)SENSOR 1 and 2
ቁ    n
⁄
ቁ × 100% 
 
11.3.2.8 Effect of compression on sensor performance during sleep challenges 
For the sleep assessment periods during visits 4 & 5, compression may occur to the sensor 
site when the subject is sleeping at night. The system’s difference and agreement with 
reference and between system precision will be compared between the night time and the 
day time (Tables 10A and 10B in APPENDIX 1).  
 
 
12 DEVICE ACCOUNTABILITY 
 
Only an approved Investigator and investigational site may receive and use the Senseonics 
CGM System. The product will be packaged and labeled to clearly indicate that it is for clinical 
investigational use only, and the investigational device must only be used in subjects enrolled 
in this investigation. The Investigator is responsible for investigational product accountability, 
reconciliation, and record maintenance. The accountability includes storage of the 
investigational supplies in a secured location according to the conditions set forth for the 
device on the label. The investigator must maintain investigational product accountability 
records throughout the course of the investigation including receipt, use, and final disposition 
of investigational inventory. The accountability includes documenting the part number, lot 
number, serial number (and expiration date for sterile components) of investigational device 
(as applicable) assigned to each subject. 
All investigational product (used or not used) must be returned to Senseonics unless 
otherwise instructed by Senseonics. Explanted Sensors will also be returned to Senseonics 
using Biohazard Return instructions and supplies. 
 
13 ETHICAL AND REGULATORY CONSIDERATIONS 
 
13.1 Statement of Compliance and Good Clinical Practice 
This clinical investigation will be conducted in compliance with the principles that have their 

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origin in the Declaration of Helsinki (Revision 6, 2008), this clinical investigation plan, 
requirements of the approving IRB or EC, US Code of Federal Regulations applicable to 
clinical studies, ICH GCP E6, ISO 14155 and other applicable regulatory requirements. 
 
This clinical investigation will not be initiated until approval has been obtained from the FDA 
or local regulating authority as well as IRB/ EC. No deviation from the protocol will be 
implemented without the prior review and approval of the Sponsor and /or IRB except 
where it may be necessary to eliminate an immediate hazard to a subject. In such case, the 
deviation will be reported to the IRB and Sponsor per their reporting requirements. 
 
13.2 Informed Consent and Investigational Review Board 
The Investigator is responsible for assuring that informed consent is obtained from each 
subject or (legally authorized representative) prior to participation in the clinical 
investigation, according to the local clinical site’s IRB  and applicable regulatory 
requirements. 
The Investigator will prepare an informed consent form (ICF) in accordance with this 
protocol and applicable regulatory requirements. Prior to the start of the study or revision 
to study, the informed consent form will be reviewed by the Sponsor for consistency with 
protocol, and then must be submitted to and approved by the IRB. A copy of the final IRB 
approved consent form and notification of approval of the clinical protocol must be 
received and approved by the Sponsor prior to start of study or revision to study. Timely 
approvals for the continuation of the trial as well as the informed consent form at each 
clinical site must also be forwarded to the Sponsor. 
While an Investigator may discuss  general availability of the investigation with a 
prospective subject without first obtaining consent, informed consent must be obtained 
from a subject prior to initiation of any clinical procedures dictated by the protocol (e.g., 
pregnancy testing) that are performed solely for the purpose of determining eligibility to 
participate in the clinical investigation. 
The informed consent process includes both verbal and written explanation. Subjects must 
be fully counseled and informed of their options, risks and benefits, and have every 
opportunity to ask questions about participation in the investigation. Insurance coverage 
will be explained to the subject. This process includes a thorough explanation of the 
informed consent document that the subject will be asked to sign acknowledging that they 
understand and desire to participate in the investigation. The subject will be provided a 
copy of the signed informed consent form. The original ICF remains at the investigational 
site. 

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If new information regarding the investigational device becomes available and/or the 
protocol changes and this information can significantly affect a subject’s future health and 
medical care, subjects will be informed of the information and may be asked to sign a 
revised informed consent form. 
 
The Investigator will notify the Sponsor within 5 working days, a withdrawal of approval by 
the reviewing IRB of the investigator’s part of an investigation.  
 
13.3 Payment for Participants 
Subjects will be compensated for their time and travel expenses as detailed in the Informed 
Consent document. 
 
13.4 Amendments to the Protocol 
Investigators may not modify this protocol without obtaining written concurrence of the 
sponsor and approval by the IRB and required regulatory authorities. 
 
13.5 Sponsor Responsibilities 
As the Sponsor of this clinical trial, Senseonics Incorporated has the overall responsibility for 
the conduct of the clinical trial, including assurance that the study meets the regulatory 
requirements of the appropriate regulatory bodies. In this study, the Sponsor will have 
certain direct responsibilities and may delegate other responsibilities to another 
organization such as a Contract Research Organization (CRO). 
The Sponsor will submit all reports required by the appropriate regulatory authorities, 
including unanticipated adverse device effects, withdrawal of IRB approval, current 
investigators list, annual progress reports, final report, and protocol violations. 
The Sponsor will select the qualified Investigators who will conduct clinical investigations of 
medical devices under 21 CFR Part 812 and applicable local and regulations. 
The Sponsor will maintain copies of correspondence, all data, device shipment records, 
adverse events, device accountability, and required study documentation as required by 
the appropriate regulatory authorities. 
 
13.6 Investigator Responsibilities and Delegation of Study-Specific Tasks 
The Investigators commit themselves to conducting the investigation in accordance with 
the Clinical Trial Agreement, Protocol, and applicable FDA and local regulations for patient 
safety and control of investigational devices. Investigators are responsible for submitting 
and obtaining initial and continuing review of the clinical trial at least annually unless 
otherwise directed by the IRB, and completing all required reports. 

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Study-specific tasks may be delegated by an Investigator to individuals who are qualified by 
education, training, and experience. However, the Principal Investigator remains 
responsible for the conduct of the clinical trial. 
A Delegation of Authority Log will be maintained to document the study personnel and their 
roles and delegated tasks. No study-specific tasks may be performed prior to the 
appropriate training and completion of the Delegation of Authority Log. 
Records to be maintained by the Investigator include, but are not limited to: clinical trial 
investigational plan and all amendments, signed clinical study agreement, signed financial 
disclosure forms, IRB communication including approvals and informed consent forms, IRB 
membership list, correspondence related to the trial, curriculum vitae, delegation of 
authority documentation, sponsor sign-in documentation, laboratory certification and 
normal ranges, reports (including annual reports, final reports). For each subject enrolled: 
signed informed consent form(s), all completed case report forms with source 
documentation supporting the data, and supporting documentation related to any 
complication or adverse event. 
 
13.7 Training 
The Sponsor or designee will provide training to the investigator(s) and site personnel. 
Training will occur before the first device use and/or protocol-specific task. To ensure 
protocol and regulatory compliance as well as accurate data collection, site training will 
include a detailed review of the protocol, device accountability, CRF completion, 
investigation-specific procedures, monitoring logistics, and regulatory requirements. The 
appropriate investigator(s) and site personnel will be trained on procedures for insertion 
and removal of the Sensor by qualified personnel (e.g. trained investigators and 
investigative staff, Sponsor personnel) using appropriate training materials (e.g. 
investigator meetings,  , demonstrations, labs, webinars, etc.). Only the personnel 
responsible for the insertion and removal of the sensor will be required training on the 
insertion/removal procedures. 
Documentation of site personnel qualification and training will be maintained in the site’s 
clinical files and Sponsor files. Training will be updated as appropriate, for example for 
protocol amendments, revisions, and any device changes. 
 
13.8 Protocol Compliance 
Senseonics will evaluate protocol deviations and Subject compliance during the 
investigation. Individual event corrective and preventive actions may be recommended. 

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Deviations occurring across investigational sites will be reviewed by Senseonics on an 
ongoing basis to determine if more global preventive actions may be required. 
 
13.9 Protocol Deviation 
Ongoing monitoring of protocol compliance will be performed for each site. The sponsor 
has the right to suspend enrollment at sites deemed to have excessive protocol compliance 
issues. 
The investigator agrees to conduct the investigation in accordance with this protocol. An 
investigator must not intentionally deviate from the protocol without prior approval from 
the Sponsor, except when necessary to eliminate apparent immediate hazards to a subject, 
or when the changes(s) involves logistical  or administrative aspects of the study and do not 
affect the subject’s rights, safety and well-being, or the scientific integrity of the study. . 
Protocol deviations are documented on CRFs. Investigators will also adhere to procedures 
for reporting investigation deviations to the IRB in accordance with the specific IRB 
reporting policies and procedures. 
Under emergency circumstances, deviations from this protocol to protect the rights, safety 
and well-being of a subject may proceed without prior approval of the Sponsor and the IRB. 
Such deviations must be reported to the Sponsor within 48 hours of occurrence and 
respective regulatory bodies as soon as possible per applicable reporting requirements. 
 
13.10 Document Storage and Retention 
All study records will be maintained according to local regulatory requirements or for two 
years after marketing approval is obtained or two years after the site is notified that this 
research protocol has been terminated by the Sponsor. Record retention dates will be 
provided to all parties concerned by the Sponsor. Following the end of the retention 
period, all records may be destroyed (papers shredded or deleted from electronic media). 
It is the investigator’s responsibility to meet applicable local retention requirements for all 
investigation-related records and the investigator must notify Senseonics prior to 
discarding any of these records. 
 
13.11 Confidentiality of Data 
All information and data pertaining to the clinical trial will be considered confidential. Only 
authorized personnel may have access to the confidential data. Authorized personnel from 
the regulatory authorities have the right to inspect and copy all records pertinent to this 
trial. All data used in the analysis and reporting of this evaluation will be without 
identifiable reference to the Subject. 

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13.12 Clinical Study Monitoring 
The Sponsor or its designee will conduct investigational site monitoring visits to ensure 
compliance with the protocol and the Investigator Agreement. 
Monitoring will be carried out in compliance with 21 CFR Part 812,  ISO 14155, Good Clinical 
Practice (GCP) Guidelines, regulatory requirements, written standard operating procedures, 
and an investigation-specific Monitoring Plan. The Monitoring Plan will specify the relative 
frequency, scope, and general conduct of monitoring visits as well as identify any relevant 
study-specific monitoring responsibilities. 
The monitoring responsibilities may be delegated by the Sponsor to a Clinical Research 
Organization (CRO). Monitors for this study must be qualified by education, experience, and 
training. The qualifications of monitors will be kept on file. 
The investigator or their designee will permit access to subject source documents and study 
documentation in order to verify that information on case report forms (CRFs) is accurate 
and complete and study documentation is up to date and complete. 
 
13.13 Medical Monitor 
A Medical Monitor will be appointed to provide safety oversight for the investigation. The 
appointed Medical Monitor will be an independent physician with relevant therapeutic and 
medical expertise that is not participating as a clinical investigator in the clinical trial and 
does not have a financial, scientific, or other conflict of interest with the clinical trial. 
 
Specific responsibilities of the Medical Monitor will include the following: 
• Provide medical and scientific input to review applicable clinical data, subject medical 
safety data and laboratory values 
• Maintain ongoing assessment of the safety profile of the investigational device during 
the investigation 
• Provide medical surveillance and evaluation of all device or procedure related adverse 
events, including serious adverse events (SAEs) and unanticipated adverse device effects 
(UADEs) on a periodic basis  
• Ensure implementation of the study stopping rule(s) 
• Adverse event adjudication including: 
o Assess and assign device and procedure relatedness used in the safety endpoint 
analysis 
o Provide adverse event categorization and physiologic system assignment 
o Provide adverse event characterization for Severity and if anticipated or 
unanticipated  
 
• Other safety management/oversight as called upon by Senseonics during the study 

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In addition to engagement in individual adverse event adjudication, the Medical Monitor will 
complete a safety data review of summary data across all sites to include: 
• Adverse event summaries 
• Adverse event endpoint review 
• Unanticipated adverse device effects review  
• Summary of protocol deviations, device deficiencies, subject terminations, and subject 
withdrawals related to device or procedure safety  
• Study stopping rule assessment 
 
Safety data review procedures will comply with the Safety Management Plan, which will 
include processes for individual event review and adjudication, periodic   safety data review 
and safety surveillance, and adverse event reporting requirements. Safety data review 
minutes will be documented in the study file. 
 
13.14 Auditing 
The Sponsor or designee may perform periodic site and study file audits to evaluate 
compliance with standards and Good Clinical Practice. Audits may include, but are not 
limited to, device supply, presence of required documents, the informed consent process, 
and comparison of CRFs with source documents. The investigator agrees to participate 
with audits conducted at a reasonable time, in a reasonable manner. 
 
13.15 Insurance and Indemnity 
Clinical trial insurance will be secured prior to investigation initiation. 
 
 
14 FINAL REPORT 
 
Upon completion or termination of the study, the PI must submit a final written report to the 
Sponsor and IRB as required by the regulations. The report should be submitted within 
approximately 3 months (90 days) of completion or termination of the trial. 
 
The Sponsor will submit a final report as required by the appropriate regulatory authorities. 
 
 
15 PUBLICATION POLICY 
 
Publication by Senseonics 
Senseonics may at any time publish the results of and information pertaining to the 
investigation Subject only to ensure compliance with regulatory requirements pertaining to 
subject protected health information. 

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Publication by the Investigational Sites 
Investigators will be invited to publish the results of this clinical investigation. The conditions 
under which an investigator may publish results from this clinical investigation in any form 
are defined in detail in the clinical trial agreement. 
 
 

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16 REFERENCES 
1. Rewers M, Pihoker C, Donaghue K, Hanas R, Swift P, Klingensmith GJ. Assessment and 
monitoring of glycemic control in children and adolescents with diabetes. Pediatr Diabetes. 
2009 Sep;10 Suppl 12:71-81. 
2. Weinstein RL, Schwartz SL, Brazg RL, Bugler JR, Peyser TA, McGarraugh GV. Accuracy of 
the 5- day FreeStyle Navigator Continuous Glucose Monitoring System: comparison with 
frequent laboratory reference measurements. Diabetes Care. 2007 May;30(5):1125-30. 
3. Zisser HC, Bailey TS, Schwartz S, Ratner RE, Wise J. Accuracy of the SEVEN continuous 
glucose 
monitoring system: comparison with frequently sampled venous glucose 
measurements. J Diabetes Sci Technol. 2009 Sep 1;3(5):1146-54. 
4. Garg S, Zisser H, Schwartz S, Bailey T, Kaplan R, Ellis S, Jovanovic L. Improvement in 
glycemic 
excursions with a transcutaneous, real-time continuous glucose Sensor: a 
randomized controlled trial. Diabetes Care. 2006 Jan;29(1):44-50. 
5. Clinical and Laboratory Standards Institute. Performance Metrics for Continuous 
Interstitial Glucose Monitoring: Approved Guideline. CLSI Document POCT05-A. 
Wayne, PA. 2008. 
6. In-vitro Diagnostic Test Systems-Requirements for Blood Glucose Monitoring Systems for 
Self Testing in Managing Diabetes Mellitus. ISO 15197:2003. Geneva. 
7. U.S. Food and Drug Administration. Content of Premarket Submissions for Management 
of Cybersecurity in Medical Devices. Guidance. 2014 
8. U.S. Food and Drug Administration. The Content of Investigational Device Exemption (IDE) 
and Premarket Approval (PMA) Applications for Artificial Pancreas Device Systems. Draft 
Guidance. 2011. 
9. U.S. Food and Drug Administration. Design Considerations for Pivotal Clinical Investigations 
for Medical Devices. 2013. 
10. Clinical investigation of medical devices for human subjects — Good clinical 
practice. ISO 14155:2011. Geneva. 
11.   Kruskal WH, Wallis WA. Use of ranks in one-criterion variance analysis. JASA. 1952;47:583–
621. 
12.   Parkes JL, Slatin SL, Pardo S, Ginsberg BH. A new consensus error grid to evaluate the 
clinical significance of inaccuracies in the measurement of blood glucose. Diabetes Care. 
2000 Aug;23(8):1143-8.    
13. Berwick V, Cheek L, Ball J. Statistics review 12: Survival analysis. Crit Care. 2004;8:389–94. 
14. CLSI. Performance Metrics for Continuous Interstitial Glucose Monitoring; Approved 
Guideline. CLSI document POCT05-A. Wayne, PA: Clinical and Laboratory Standards 
Institute; 2008. 
 
 

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17 APPENDIX 1 EXAMPLE FIGURES AND TABLES OF STATISTICAL ANALYSIS RESULTS 
 
Figure 1. Subject Accountability (Sample Data) 
109 subjects consented 
 
 
 
 
 13 subjects (01-001, 04-002, 05-001, 06-001, 05-012, 04-011, 02-007, 02-008, 07-002, 
07-006, 05-021, 07-008, and 07-009) had screen failure 
 
 15 subjects (01-005, 01-006, 01-007, 01-009, 01-010, 01-012, 01-013, 01-014, 04-003, 
04-004, 05-003, 03-002, 05-015, 02-011, and 07-003) withdrew consent due to 
exceeding screening window 
 
 
 
81 subjects completed sensor insertion 
 
 
 
 
 10 subjects (02-001, 03-001, 04-001, 05-002, 06-004, 01-002, 01-003, 01-004, 01-008, 
and 01-011) are the training subjects 
 
 
 
71 subjects are included in the effectiveness and safety endpoints 
 
 
 
71 subjects completed Day 1 Visit 
 
 
 
 
 2 subject (01-017 and 04-009) withdrew consent 
 
 1 subject (03-010) withdrew consent due to AE 
 
 
 
68 subjects completed Day 7 Visit 
 
 
 
 
 2 subjects (04-008 and 06-017) completed study with sensor retirement alert 
 
 
 
66 subjects completed Day 14 Visit   
 
Table 1. Investigational Transmitter Deficiencies (Sample Data) 
Type of Transmitter Deficiency 
Number Reported 
% of Total 
Package Label 
0 
0% 
Product Defect 
21 
87.5% 
Damaged Package 
0 
0% 
Product Safety 
0 
0% 
Product Performance 
1 
4.2% 
Other 
2 
8.3% 
 
Table 2. Investigational Sensor Deficiencies (Sample Data) 
Type of Sensor Deficiency 
Number Reported 
% of Total 
Package Label 
0 
0% 
Product Defect 
21 
87.5% 
Broken Sterile Seal 
0 
0% 
Damaged Package 
0 
0% 
Product Safety 
0 
0% 

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Product Performance 
1 
4.2% 
Other 
2 
8.3% 
 
Table 3. Summary of Serious Adverse Events (Sample Data)  
SAEs by 
Relationship to 
Study 
Number 
of SAEs 
Number of 
Patients with 
SAEs (%; 95% 
Confidence 
Interval) 
All SAEs 
1 
1 (1.4%; 0.0%-
7.6%) 
Device Related 
SAEs 
0 
0 (0.0%; 0.0%-
5.1%) 
Sensor 
Insertion/Removal 
Procedure Related 
SAEs 
0 
0 (0.0%; 0.0%-
5.1%) 
Unrelated to 
Study SAEs 
1 
1 (1.4%; 0.0%-
7.6%) 
 
Table 4A. Other Safety Endpoint (Sample Data) 
Type of Incidence 
Number 
of 
Incidents 
Number (%) of 
Subjects with 
Incidents 
Incidence of device-related or insertion/removal 
procedure-related serious adverse events over the 
operating life of the Sensor  
0 
0 (0.0%) 
Incidence of insertion/removal procedure or 
device-related adverse events in the clinic and 
during home use 
12 
11 (15.5%) 
Incidence of all adverse events in the clinic and 
during home use 
35 
24 (26.6%) 
Incidence of hospitalizations due to hypoglycemia, 
hyperglycemia, or ketoacidosis occurring during 
home use 
0 
0 (0.0%) 
Incidence of reported hypoglycemic and 
hyperglycemic events occurring during home use 
2 
2 (2.8% 

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Table 4B. Other Safety Endpoint for Subjects between 18 and 20 Years Old (Sample Data) 
Type of Incidence 
Number 
of 
Incidents 
Number (%) of 
Subjects with 
Incidents 
Incidence of device-related or insertion/removal 
procedure-related serious adverse events over the 
operating life of the Sensor  
0 
0 (0.0%) 
Incidence of insertion/removal procedure or 
device-related adverse events in the clinic and 
during home use 
12 
11 (15.5%) 
Incidence of all adverse events in the clinic and 
during home use 
35 
24 (26.6%) 
Incidence of hospitalizations due to hypoglycemia, 
hyperglycemia, or ketoacidosis occurring during 
home use 
0 
0 (0.0%) 
Incidence of reported hypoglycemic and 
hyperglycemic events occurring during home use 
2 
2 (2.8% 
 
Table 4C. Safety Endpoint for Subjects between 21 and 44 Years Old (Sample Data) 
Type of Incidence 
Number 
of 
Incidents 
Number (%) of 
Subjects with 
Incidents 
Incidence of device-related or insertion/removal 
procedure-related serious adverse events over the 
operating life of the Sensor  
0 
0 (0.0%) 
Incidence of insertion/removal procedure or 
device-related adverse events in the clinic and 
during home use 
12 
11 (15.5%) 
Incidence of all adverse events in the clinic and 
during home use 
35 
24 (26.6%) 

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Incidence of hospitalizations due to hypoglycemia, 
hyperglycemia, or ketoacidosis occurring during 
home use 
0 
0 (0.0%) 
Incidence of reported hypoglycemic and 
hyperglycemic events occurring during home use 
2 
2 (2.8% 
 
Table 4D. Safety Endpoint for Subjects between 45 and 65 Years Old (Sample Data) 
Type of Incidence 
Number of 
Incidents 
Number (%) of 
Subjects with 
Incidents 
Incidence of device-related or insertion/removal 
procedure-related serious adverse events over the 
operating life of the Sensor  
0 
0 (0.0%) 
Incidence of insertion/removal procedure or 
device-related adverse events in the clinic and 
during home use 
12 
11 (15.5%) 
Incidence of all adverse events in the clinic and 
during home use 
35 
24 (26.6%) 
Incidence of hospitalizations due to hypoglycemia, 
hyperglycemia, or ketoacidosis occurring during 
home use 
0 
0 (0.0%) 
Incidence of reported hypoglycemic and 
hyperglycemic events occurring during home use 
2 
2 (2.8% 
 
Table 4E. Safety Endpoint for Subjects over 65 Years Old (Sample Data) 
Type of Incidence 
Number of 
Incidents 
Number (%) of 
Subjects with 
Incidents 
Incidence of device-related or insertion/removal 
procedure-related serious adverse events over the 
operating life of the Sensor  
0 
0 (0.0%) 
Incidence of insertion/removal procedure or 
12 
11 (15.5%) 

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device-related adverse events in the clinic and 
during home use 
Incidence of all adverse events in the clinic and 
during home use 
35 
24 (26.6%) 
Incidence of hospitalizations due to hypoglycemia, 
hyperglycemia, or ketoacidosis occurring during 
home use 
0 
0 (0.0%) 
Incidence of reported hypoglycemic and 
hyperglycemic events occurring during home use 
2 
2 (2.8% 
 
 
Table 5. Full List of Adverse Events (Sample Data) 
Descriptions 
 
ID 
AE Description 
1 
1-16 Depressive period 
2 
1-22 Hypoglycaemic episode during the night, patient had to be assisted to drink glucose to regain full conciousness. 
3 
1-22 Reduced vision due to ocular ischaemia 
4 
1-23 Contact dermatitis at the precise location of the transmittersticker. left arm - Dermatitis has healed 
5 
2-02 Cold and runny nose - allergies? ?hayfever 
 
Characteristics 
 
ID 
AE 
Category 
AE Physiologic 
System 
Implant 
Date 
Date 
AE 
Onset 
Resolution 
Date 
Status 
Seriousness 
Severity 
Device 
Related 
Procedure 
Implant/Removal 
Related 
1 1-16 
Psychologic
al disorder 
Other 
04-DEC-
2014 
22-
DEC-
2014 
31-DEC-
2014 
Resolved Not SAE 
Moderate 
Possibly 
Related 
Not Related 
2 1-22 
Hypoglycem
ic Event 
Endocrine 
20-JAN-
2015 
29-
JAN-
2015 
29-JAN-
2015 
Resolved Not SAE 
Moderate 
Not 
Related 
Not Related 
3 1-22 
Ocular 
ischemia 
HEENT 
20-JAN-
2015 
24-
DEC-
2014 
. 
Ongoing 
Not SAE 
Moderate 
Not 
Related 
Not Related 
4 1-23 
Dermatitis 
Dermatological 
20-JAN-
2015 
28-
FEB-
2015 
18-MAR-
2015 
Resolved Not SAE 
Moderate 
Definitely 
Related 
Not Related 

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5 2-02 
Allergy - 
Seasonal 
HEENT 
19-JAN-
2015 
01-
FEB-
2015 
16-FEB-
2015 
Resolved Not SAE 
Mild 
Not 
Related 
Not Related 
 
Table 6A.  CGM System Difference to YSI within YSI Glucose Range (Sample Table) 
YSI Glucose 
Ranges 
(mg/dL) 
Number of 
Paired CGM-
YSI 
Mean Relative 
Difference (%) 
Median 
Relative 
Difference (%) 
Mean Absolute 
Relative 
Difference (%) 
Median Absolute 
Relative 
Difference (%) 
Overall 
 
 
 
 
 
<40* 
 
 
 
 
 
40-60* 
 
 
 
 
 
61-80* 
 
 
 
 
 
81-180 
 
 
 
 
 
181-300 
 
 
 
 
 
301-350 
 
 
 
 
 
351-400 
 
 
 
 
 
>400 
 
 
 
 
 
*For YSI ≤80 mg/dl, the differences in mg/dl are included instead of percent difference (%). 
 
Table 6B.  CGM System Difference to YSI within CGM System Glucose Range (Sample Table) 
CGM System 
Glucose 
Ranges 
(mg/dL) 
Number of 
Paired CGM-
YSI 
Mean Relative 
Difference (%) 
Median 
Relative 
Difference (%) 
Mean Absolute 
Relative 
Difference (%) 
Median Absolute 
Relative 
Difference (%) 
Overall 
 
 
 
 
 
40-60* 
 
 
 
 
 
61-80* 
 
 
 
 
 
81-180 
 
 
 
 
 
181-300 
 
 
 
 
 
301-350 
 
 
 
 
 
351-400 
 
 
 
 
 
*For CGM ≤ 80 mg/dL, the differences in mg/dL are included instead of percent difference (%). 
 
Table 6C.  CGM System Agreement to Reference within YSI Glucose Ranges (Sample Table) 
YSI Glucose 
Range (mg/dL) 
Number of Paired 
Eversense™ CGM 
and YSI Reference 
Percent of CGM System Readings Within 
Percent 
15/15% of 
Reference 
Percent 
20/20% of 
Reference 
Percent 
30/30% of 
Reference 
Percent 
40/40% of 
Reference 
Percent 
Greater than 
40/40% of 
Reference 
Overall 
 
 
 
 
 
 
< 40 
 
 
 
 
 
 
40 - 60 
 
 
 
 
 
 
61 - 80 
 
 
 
 
 
 
81 - 180 
 
 
 
 
 
 
181 - 300 
 
 
 
 
 
 
301 - 350 
 
 
 
 
 
 
351 - 400 
 
 
 
 
 
 
> 400 
 
 
 
 
 
 

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Table 6D.  CGM System Agreement to Reference within CGM System Glucose Ranges (Sample 
Table) 
CGM System 
Glucose 
Range (mg/dL) 
Number of Paired 
Eversense™ CGM 
and YSI Reference 
Percent of CGM System Readings Within 
Percent 
15/15% of 
Reference 
Percent 
20/20% of 
Reference 
Percent 
30/30% of 
Reference 
Percent 
40/40% of 
Reference 
Percent 
Greater than 
40/40% of 
Reference 
Overall 
 
 
 
 
 
 
40 - 60 
 
 
 
 
 
 
61 - 80 
 
 
 
 
 
 
81 - 180 
 
 
 
 
 
 
181 - 300 
 
 
 
 
 
 
301 - 350 
 
 
 
 
 
 
351 - 400 
 
 
 
 
 
 
  
Table 7A.  Concurrence of CGM System Readings and YSI Values within YSI Glucose Ranges 
(Sample Table) 
YSI 
(mg/dL) 
Number of 
Paired 
CGM-YSI 
(n) 
Percent of Matched Pairs in Each CGM System Glucose Range for Each YSI Glucose 
Range  
CGM (mg/dL) 
40-60 
61-80 
81-120 
121-
160 
161-
200 
201-
250 
251-
300 
301-
350 
351-400 
<40 
 
 
 
 
 
 
 
 
 
 
40-60 
 
 
 
 
 
 
 
 
 
 
61-80 
 
 
 
 
 
 
 
 
 
 
81-120 
 
 
 
 
 
 
 
 
 
 
121-160 
 
 
 
 
 
 
 
 
 
 
161-200 
 
 
 
 
 
 
 
 
 
 
201-250 
 
 
 
 
 
 
 
 
 
 
251-300 
 
 
 
 
 
 
 
 
 
 
301-350 
 
 
 
 
 
 
 
 
 
 
351-400 
 
 
 
 
 
 
 
 
 
 
>400 
 
 
 
 
 
 
 
 
 
 
 
Table 7B. Concurrence of CGM System Readings and YSI Values within CGM System Ranges 
(Sample Table) 
CGM 
(mg/dL) 
Number of 
Paired 
CGM-YSI 
(n) 
Percent of Matched Pairs in Each YSI Glucose Range for Each CGM Glucose Range YSI (mg/dL) 
<40 
40-60 
61-80 
81-120 
121-
160 
161-
200 
201-
250 
251-
300 
301-
350 
351-
400 
>400 
40-60 
 
 
 
 
 
 
 
 
 
 
 
 
61-80 
 
 
 
 
 
 
 
 
 
 
 
 
81-120 
 
 
 
 
 
 
 
 
 
 
 
 
121-160 
 
 
 
 
 
 
 
 
 
 
 
 
161-200 
 
 
 
 
 
 
 
 
 
 
 
 
201-250 
 
 
 
 
 
 
 
 
 
 
 
 

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CGM 
(mg/dL) 
Number of 
Paired 
CGM-YSI 
(n) 
Percent of Matched Pairs in Each YSI Glucose Range for Each CGM Glucose Range YSI (mg/dL) 
<40 
40-60 
61-80 
81-120 
121-
160 
161-
200 
201-
250 
251-
300 
301-
350 
351-
400 
>400 
251-300 
 
 
 
 
 
 
 
 
 
 
 
 
301-350 
 
 
 
 
 
 
 
 
 
 
 
 
351-400 
 
 
 
 
 
 
 
 
 
 
 
 
 
Table 8. CGM System Accuracy by Visit Number (Sample Table) 
Day Number 
Number of 
Paired 
CGM-YSI 
Mean 
Absolute 
Relative 
Difference 
(%) 
Median 
Absolute 
Relative 
Difference 
(%) 
Percent of CGM System Readings Within 
Percent 
15/15% 
of 
Reference 
Percent 
20/20%  
of 
Reference 
Percent 
30/30%  
of 
Reference 
Percent 
40/40% 
of 
Reference 
Percent 
Greater than 
40/40% of 
Reference 
Day 1 
 
 
 
 
 
 
 
 
Day 7 
 
 
 
 
 
 
 
 
Day 14 
 
 
 
 
 
 
 
 
Day 30 
 
 
 
 
 
 
 
 
Day 60 
 
 
 
 
 
 
 
 
Day 90 
 
 
 
 
 
 
 
 
 
Table 9. CGM System between System Precision (Sample Table) 
Level of Mean 
Glucose (mg/dL) 
Mean Difference 
(Sensor 1 - Sensor 2) 
(mg/dL) 
SD of Difference 
(mg/dL) 
N Pairs 
<= 70 
 
 
 
71-180 
 
 
 
> 180 
 
 
 
All 
 
 
 
 
PARD 
 
PCV 
 
 
Table 10A.  CGM System Performance during Sleep Challenges (Sample Table) 
Night Time 
(Y/N) 
Number of 
Paired 
CGM-YSI 
Mean 
Absolute 
Relative 
Difference 
(%) 
Median 
Absolute 
Relative 
Difference 
(%) 
Percent of CGM System Readings Within 
Percent 
15/15% 
of 
Reference 
Percent 
20/20%  
of 
Reference 
Percent 
30/30%  
of 
Reference 
Percent 
40/40% 
of 
Reference 
Percent 
Greater than 
40/40% of 
Reference 
Y 
 
 
 
 
 
 
 
 
N 
 
 
 
 
 
 
 
 
 
Table 10B.  CGM System between System Precision during Sleep Challenges (Sample Table) 
Night Time 
(Y/N) 
N Pairs 
PARD 
Y 
 
 
N