DEXCOM G4 PLATINUM CONTIUOUS GLUCOSE MONITORING SYSTEM

P120005 · Dexcom, Inc. · MDS · Oct 5, 2012 · Clinical Chemistry

Device Facts

• Record ID: P120005
• Device Name: DEXCOM G4 PLATINUM CONTIUOUS GLUCOSE MONITORING SYSTEM
• Applicant: Dexcom, Inc.
• Product Code: MDS · Clinical Chemistry
• Decision Date: Oct 5, 2012
• Decision: APWD
• Device Class: Class 3

Intended Use

The Dexcom G4 PLATINUM Continuous Glucose Monitoring System is a glucose monitoring device indicated for detecting trends and tracking patterns in persons (age 18 and older) with diabetes. The system is intended for single patient use and requires a prescription. The Dexcom G4 PLATINUM System is indicated for use as an adjunctive device to complement, not replace, information obtained from standard home glucose monitoring devices. The Dexcom G4 PLATINUM System aids in the detection of episodes of hyperglycemia and hypoglycemia, facilitating both acute and long-term therapy adjustments, which may minimize these excursions. Interpretation of the Dexcom G4 PLATINUM System results should be based on the trends and patterns seen with several sequential readings over time.

Device Story

System monitors interstitial fluid glucose; consists of subcutaneous sensor, transmitter, and handheld receiver. Sensor uses glucose oxidase enzyme to convert glucose to electrical current; transmitter sends signal wirelessly to receiver every 5 minutes. Receiver processes signal, displays glucose values, trend graphs, and rate-of-change arrows. User calibrates system twice daily via fingerstick blood glucose meter. Used by patients in home/clinic settings; data can be uploaded to PC via Dexcom Studio software for clinician/patient review. Alerts/alarms notify users of high/low glucose levels. Provides continuous glucose tracking to aid in therapy adjustments and hypoglycemia/hyperglycemia detection.

Clinical Evidence

Pivotal open-label, non-randomized, single-arm, multi-center study (IDE #G110107/S001) with 72 subjects (age >18). Primary endpoint: accuracy vs. YSI reference. 9,152 matched pairs collected. 82% of readings within ±20 mg/dL (for YSI <80 mg/dL) or ±20% (for YSI ≥80 mg/dL). Mean absolute percent difference (MARD) 13.3%. No serious adverse device events reported; 22 mild device-related skin irritations. Bench testing confirmed mechanical integrity, biocompatibility (ISO 10993-1), and electromagnetic compatibility.

Technological Characteristics

System components: sterile sensor probe (glucose oxidase), transmitter, receiver. Sensor: 26-gauge introducer needle, 7-day wear. Transmitter: RF wireless communication (2.4 GHz). Receiver: LCD display, rechargeable battery, USB interface. Sterilization: E-beam radiation (VDmax 25 method). Biocompatibility: ISO 10993-1 compliant. Connectivity: proprietary wireless link to receiver; USB for PC data transfer.

Indications for Use

Indicated for persons age 18 and older with diabetes to detect trends and track glucose patterns as an adjunct to standard home glucose monitoring. Contraindicated for use during MRI, CT scans, or diathermy. Acetaminophen use may cause false high readings.

Regulatory Classification

Identification

The device is a glucose-monitoring device indicated for detecting trends and tracking patterns in adults (age 18 and older) with diabetes. The device is indicated for use as an adjunctive device to complement, not replace, information obtained from standard home glucose monitoring devices. The system aids in the detection of episodes of hyperglycemia and hypoglycemia, facilitating both acute and long-term therapy adjustments.

Reference Devices

• SEVEN PLUS

Submission Summary (Full Text)

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SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

I. GENERAL INFORMATION

Device Generic Name: Continuous Glucose Monitoring System
Device Trade Name: Dexcom G4 PLATINUM Continuous Glucose Monitoring System
Device Procode: MDS
Applicant's Name and Address: Dexcom, Inc.
6340 Sequence Drive
San Diego, CA 92121
Date(s) of Panel Recommendation: None
Premarket Approval Application (PMA) Number: P120005
Date of FDA Notice of Approval: October 5, 2012
Expedited: not applicable

II. INDICATIONS FOR USE

The Dexcom G4 PLATINUM Continuous Glucose Monitoring System is a glucose monitoring device indicated for detecting trends and tracking patterns in persons (age 18 and older) with diabetes. The system is intended for single patient use and requires a prescription.

The Dexcom G4 PLATINUM System is indicated for use as an adjunctive device to complement, not replace, information obtained from standard home glucose monitoring devices.

The Dexcom G4 PLATINUM System aids in the detection of episodes of hyperglycemia and hypoglycemia, facilitating both acute and long-term therapy adjustments, which may minimize these excursions. Interpretation of the Dexcom G4 PLATINUM System results should be based on the trends and patterns seen with several sequential readings over time.

III. CONTRAINDICATIONS

- Remove the Dexcom G4 PLATINUM sensor, transmitter, and receiver before Magnetic Resonance Imaging (MRI), Computed Tomography (CT) scan, or

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diathermy treatment. The Dexcom G4 PLATINUM System has not been tested during MRI or CT scans or with diathermy treatment. The magnetic fields and heat could damage the device so that it might not display sensor glucose readings or provide alerts, and you might miss a low or high blood glucose value.

- Taking medications with acetaminophen (such as Tylenol) while wearing the sensor may falsely raise your sensor glucose readings. The level of inaccuracy depends on the amount of acetaminophen active in your body and may be different for each person.

## IV. WARNINGS AND PRECAUTIONS

The warnings and precautions can be found in the Dexcom G4 PLATINUM Continuous Glucose Monitoring System labeling.

## V. DEVICE DESCRIPTION

The Dexcom G4 PLATINUM Continuous Glucose Monitoring System (“The System”) is a glucose monitoring device indicated for detecting trends and tracking patterns in persons (age 18 and older) with diabetes. The System is designed to provide continuous measurements of interstitial fluid glucose over the measuring range of 40 to 400 mg/dL for up to seven days of use. The claimed insertion site for the sensor is the abdomen.

Once the sensor is inserted under the skin of the abdomen and attached to the transmitter, the System requires a start-up period prior to the initial calibration. The start-up period, the time required for the Sensor to equilibrate, requires a minimum of two hours from Sensor insertion. At the end of this period, the system prompts the user to calibrate the device with fingerstick blood glucose measurements using any FDA-cleared home blood glucose meter. The user then manually enters the blood glucose values using a menu-driven interface on the device. After calibration, the System provides a glucose reading once every 5 minutes as well as trend graphs which are updated periodically. The System also has programmable High and Low Glucose Alerts and a non-changeable Low Glucose Alarm set at 55 mg/dL.

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The System consists of the following components: Sensor, Transmitter, and Receiver:

Dexcom G4 PLATINUM Receiver

Dexcom G4 PLATINUM Sensor

Dexcom G4 PLATINUM Transmitter

## A. Dexcom G4 PLATINUM Sensor

The G4 PLATINUM Sensor (the Sensor) is comprised of a sensor applicator, an adhesive pad, transmitter mount and the sensor probe. The sensor can be worn for up to 7 days. The Sensor is a sterile device inserted by the user into the abdominal subcutaneous tissue using the applicator. The applicator is adhered to the surface of the skin with a standard medical grade adhesive pad. The applicator contains a 26-gauge introducer needle that contains the sensor probe. The needle is not exposed, or even visible, to the user during the insertion process. After deployment of the introducer needle, the needle is retracted back into the applicator. The sensor probe remains beneath the surface of the skin and uses the enzyme glucose oxidase to convert the glucose in the interstitial fluid around the sensor into an electrical current proportional to the ambient glucose concentration.

The applicator is detached and disposed by the user, exposing a transmitter mount ready for placement of the transmitter.

## B. Dexcom G4 PLATINUM Transmitter

The G4 PLATINUM Transmitter (the Transmitter) is a miniature radio transmitter operating at an internationally-accepted radiofrequency. After sensor insertion and removal of the applicator, the user manually places the Transmitter into the transmitter mount on the adhesive pad already attached to the skin. The Transmitter contains all the electrical circuitry necessary for the operation of the electrochemical sensor and also all the radiofrequency circuitry necessary to transmit the Sensor signal to the Receiver. The Transmitter collects the small electrical current from the

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Sensor and transmits the Sensor signal wirelessly to the Receiver at regular 5-minute intervals. The Transmitter is reusable and can be used for repeated 7-day sessions by a single-user over the lifetime of the battery encased in the device.

## C. Dexcom G4 PLATINUM Receiver

The G4 Receiver (the Receiver) is a small hand-held device that contains an antenna and the associated electrical circuitry to receive the wireless sensor signal from the transmitter. The Receiver contains a rechargeable battery. In typical use, the Receiver may last for up to 3 days before requiring recharging. The user must maintain the Receiver within 20 feet or less of the Transmitter, which is attached to the sensor on the body. The Receiver also contains calibration and signal processing algorithms required to convert the sensor electrical signal to glucose values in mg/dL that can be displayed to the user. Calibrations are performed twice daily by the patient using measurements from standard commercially-available FDA-cleared blood glucose meter devices and manually entered into the Receiver through a simple data entry menu. After calibrating the system, the Receiver automatically displays the current glucose value, trend graphs of recent glucose values and rate of change arrows once every five minutes. The Receiver provides audible or vibratory alerts for high and low glucose values.

The configurable Receiver High and Low Glucose Alerts can be set by the user in consultation with their health care provider to provide warning when their current glucose level is outside of their target range. Dashed lines on the Receiver screen indicate the current alert level settings. The user can configure the Receiver to provide audible, vibratory or combined audible and vibratory alerts. The Receiver also contains a non-configurable low glucose alarm at 55 mg/dL to provide users additional warning of hypoglycemia.

The Receiver contains a mini-USB port for uploading Sensor data to a personal computer. Dexcom Studio software is an optional accessory data management program intended to allow the transfer of glucose data stored by the Receiver to a personal computer (PC). This software can be used to view trends, track patterns and create custom charts to display glucose trends by either clinicians or the user. The software is available for users to download from the Sponsor's website.

Please refer to the Dexcom G4 Platinum User's Guide for more detail.

## VI. ALTERNATIVE PRACTICES AND PROCEDURES

Control of diabetes can be achieved through a combination of methods and behaviors. Self behaviors include healthy eating, taking medications, as appropriate, and being active. Methods of controlling glucose levels (glycemic control) have been shown to reduce severe diabetes-related complications. Methods of monitoring glycemic control include periodic measurement of Hemoglobin A1c (HbA1c), which reflects average

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blood glucose levels over a three month period. Self-monitoring of blood glucose using glucose meters and test strips provides quantitative measurements of fingerstick blood glucose at a single point in time for patients and their healthcare providers to monitor the effectiveness of glycemic control and make more immediate treatment modifications.

Each alternative method for monitoring glycemic control has its own advantages and disadvantages. A patient should fully discuss these alternatives with his/her physician to select the method that best meets expectations and lifestyle.

There are similar CGM systems currently on the market from this sponsor and other sponsors.

## VII. MARKETING HISTORY

The Dexcom G4 PLATINUM Continuous Glucose Monitoring System has not been marketed in the United States but received a CE mark and was commercialized in the European Economic Community in July 2012. The device has not been withdrawn from marketing for any reason related to its safety or effectiveness.

## VIII. POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

The following events are possible adverse device effects of inserting a Sensor and wearing the adhesive patch: local infection, inflammation, pain or discomfort, bleeding at the glucose Sensor insertion site, bruising, itching, scarring or skin discoloration, hematoma, tape irritation, Sensor or needle fracture during insertion, wear or removal.

There are potential risks due to missed alerts, false alerts, false negative hypoglycemia and hyperglycemic readings and false positive hypoglycemia and hyperglycemia readings by the device. There are additional possible risks if the system inaccurately calculates the rate of change of glucose.

For the specific adverse events that occurred in the clinical studies, please see Section X below.

## IX. SUMMARY OF PRECLINICAL STUDIES

A summary of the non-clinical laboratory studies that were performed on the G4 Platinum CGM System are summarized below and in Tables 1-2:

### A. Laboratory Studies

**Bench Performance Testing:** Pre-clinical testing was performed on the Sensor, Transmitter and Receiver. This testing involved Environmental and safety testing and physical and mechanical testing (e.g. mechanical vibration, mechanical drop,

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temperature shock, temperature and humidity exposure, atmospheric pressure, needle insertion force, needle bond strength, and needle resistance to fracture), This testing is summarized in the Tables below (Tables 1A-1C):

Table 1A – Sensor Testing

| Test Description | Test Purpose | Acceptance Criteria | Device Configuration | Test Results |
| --- | --- | --- | --- | --- |
| Sensor Retention | Demonstrate that the minimum force required to retain the sensor meets product specification | ≥0.04 lbs | G4 Sensor Assembly; G4 Transmitter | PASS |
| Safety Card Removal | Demonstrate that the force required to remove the safety card meets product specification | ≤3 lbs | G4 Sensor Assembly | PASS |
| Needle to remain in applicator after deployment | Demonstrate that the force required to cause failure of the cannula carrier At least 1.0 lb force (lower limit) snaps meets product specifications | At least 1.0 lb force (lower limit) | G4 Applicator | PASS |
| Sensor Resistance to Fracture Under Repetitive Bending | Demonstrate that a G4 Sensor has improved resistance to fracture under repetitive bending when compared to the existing SEVEN PLUS product | Minimum 2x increase in cycles to wire failure at 0.032” bend radius compared to SEVEN PLUS | G4 Sensor; SEVEN PLUS Sensors | PASS |
| Needle Bond Strength | Demonstrate that the force required to pull the needle to failure meets product specification | At least 2.0 lb force (lower limit) | G4 Sensor and Applicator | PASS |
| Push Rod Bond Strength | Demonstrate that the force required to pull the push rod to failure meets product specification | At least 1.0 lb force (lower limit) | G4 Sensor and Applicator | PASS |
| Cannula Bond Strength | Demonstrate that the force required to pull the cannula to failure meets product specification | At least 6.5 lb force (lower limit) | G4 Sensor and Applicator | PASS |
| Deployment | Demonstrate that the plunger, cannula carrier, pushrod, needle carrier, and safety locks deploy correctly | Plunger, needle, cannula, pushrod, and safety locks operate correctly | G4 Sensor and Applicator | PASS |
| Sensor Angle Measurement | Demonstrate that the angle of the sensor meets product specification | 45°±5° | G4 Sensor and Applicator | PASS |
| Sensor Deployment Depth | Demonstrate that the depth of the Sensor below the adhesive pad meets product specification | Distal tip of the Sensor to be between 0.35” (lower limit) and 0.55” (upper limit) | G4 Sensor and Applicator | PASS |

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| Humidity Resistance | Demonstrate that the resistance to humidity meets product specification | Counts ≤6000 (187.5 pA) | G4 Transmitter; Sterilized G4 Sensor Assembly; G4 Receiver | PASS |
| --- | --- | --- | --- | --- |
| Adhesive/ Base Peel Test | Demonstrate that the pad exhibits some cohesive failure such as pad ripping following a base peel test, as per product specification | Pad must display some cohesive failure | G4 Applicator | PASS |
| Water Resistance | Demonstrate that the product meets the requirement for water resistance | Counts ≤6000 (187.5 pA) | Sterilized G4 Sensor Assembly; ;Transmitter; G4 Receiver | PASS |
| Reference Electrode Capacity | Demonstrate that the reference capacity of the G4 Sensors is sufficient to meet the intended use of 7 days of use | ≤10.0% MARD after 7 days | G4 Sensors | PASS |
| Needle Insertion Force | Demonstrate that the force required to insert a needle through a chamois meets product specification | Not to exceed 5 lb force (upper limit) | G4 Applicator | PASS |
| Cannula Withdrawal Force | Demonstrate that the force required to withdraw the cannula meets product specification | Not to exceed 7.5 lb force (upper limit) | G4 Applicator | PASS |
| Bail Snap Out Force | Demonstrate that the force required to remove the bail from the device meets product specification | ≤2.8 lbs | G4 Sensor Assembly | PASS |
| Bail Insertion Cycles | Demonstrate that the bail is capable of 3 insertion cycles | Bail to insert transmitter into sensor base 3 times with bail not falling out | G4 Sensor Assembly; G4 Transmitter | PASS |
| Applicator Body Release from Base | Demonstrate that the Applicator Body is easily removable from Sensor Base | Applicator can be easily released from base | G4 Sensor and Applicator | PASS |
| Contact Resistance | Demonstrate that the transmitter meets the product specification for Sensor contact resistance | Contact Resistance ≤5 MΩ | G4 transmitter, Sterilized G4 Sensor Assembly, and G4 Receiver | PASS |

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| Contact Resistance Change | Demonstrate that the transmitter meets the product specification for Sensor contact resistance change | Contact Resistance change ≤5 MΩ | G4 transmitter, Sterilized G4 Sensor Assembly, and G4 Receiver | PASS |
| --- | --- | --- | --- | --- |

Table 1B – Transmitter Testing

| Test Description | Test Purpose | Acceptance Criteria | Device Configuration | Test Results |
| --- | --- | --- | --- | --- |
| Operating Temperature Validation | Validate the reliable operation of the G4 Transmitter across its specified temperature range. | Each temperature test shows no less than 44 out of 45 consecutive packets are successfully transmitted by each unit under test. A packet transmission is considered successful if it has a clear status and a raw count value between 42,665 and 49,765 counts. | G4 Transmitter Assemblies | PASS |
| Humidity, Atmospheric Pressure, and Vibration Tests | Demonstrate product conformance to humidity, pressure and vibration specifications
Humidity: 10-95%, non-condensing
Pressure: 7.5±0.5 psi to 15±1.1 psi
Vibration resistance: ASD spectrum level: 0.1 G2/Hz 5-150 Hz, 3 axes, 30 minutes per axis | Humidity and Pressure Tests
Tested as variable data: 15 samples tested, with 0 failures, that must satisfy applicable tolerance limits when evaluated using the tolerance limit equations M + k*s ≤ U.
Vibration Test
Tested as attribute data: All 30 samples must pass, 0 failures in order to meet Confidence Level of 95% and Reliability of 90%. | G4 Transmitters;
G4 Sensor Assemblies;
G4 Receivers | PASS |
| Drop Resistance | Demonstrate product conformance to drop resistance specifications | The raw count reading after the drop test is within ±10% of the initial reading. The Transmitter can be held in a Sensor | G4 Transmitters | PASS |

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| | | base and there are no added scratches or defects within the Transmitter seal area. | | |
| --- | --- | --- | --- | --- |
| Water Resistance | Demonstrate product conformance to water resistance specifications (IP28) | Acceptance criteria as detailed in EN 60601-1-11:2010 | G4 transmitters | PASS |

Table 1C – Receiver Testing

| Test Description | Test Purpose | Acceptance Criteria | Device Configuration | Test Results |
| --- | --- | --- | --- | --- |
| Operating/Storage Temperature (not charging and relative humidity uncontrolled – ambient RH < 85%) | Demonstrate reliable operation of the G4 Receivers across Specified temperature | All units must demonstrate functionality with audio alarm, vibrator alarm, and transmission receipt. All units must pass the final functional testing process and all units must receive a minimum of 95% packets during testing period. | G4 Receivers; G4 Transmitters | PASS |
| Operating Storage Humidity | Demonstrate reliable operation of the G4 Receivers across its specified humidity range of 10-95%. | All units must demonstrate functionality with audio alarm, vibrator alarm, and transmission receipt. All units must pass the final functional testing process and all units must receive a minimum of 95% packets during testing period. | G4 Receivers; G4 Transmitters | PASS |
| Operating Storage Pressure (temperature and humidity uncontrolled ambient: 20°C-5°C and relative humidity | Operating/Storage Pressure (temperature and humidity uncontrolled ambient: 20°C-5°C and relative humidity between 20% and 90%) | All units must demonstrate functionality with audio alarm, vibrator alarm, and transmission receipt. All units must pass the final functional testing process and all units must receive | G4 Receivers: G4 Transmitters | PASS |

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| between 20% and 90%) | | a minimum of 95% packets during testing period. | | |
| --- | --- | --- | --- | --- |
| Drop Resistance | Verify compliance to the product requirement regarding drop resistance with and without the carrying case | All units must pass the final functional test and have no signs of a hazardous condition. | G4 Receiver; G4 Receiver carrying case | PASS |
| Ingress Protection | Demonstrate that the G4 Receiver (with USB door closed) is protected against 15 degree dripping and 12.5 mm object access (IP22) | Receiver must meet acceptance criteria per applicable standard, IEC 60601-1-11 G4 Receiver with USB access door closed. | G4 Receiver | PASS |
| Battery Verification | Demonstrate product conformance to the general performance of the battery, including battery charging ability at temperature, ability to retain time with the backup battery, accuracy of the battery gauge, confirmation of power on ability following battery discharge, and charge times using a wall charger and powered USB port. | Operational Temperature While Charging: All units must fully charge to 100% at 40°C. Time Retention: All units must retain time for a minimum of 3 days while in Shutdown. Battery Gauge: accuracy within ±25% Power On: All units must Power On when connected to a charger after the battery has been depleted. Wall Charger Charge Time: fully charged after 3 hours Power USB Port Charge Time: fully charged after 5 hours | G4 Receivers; G4 Receiver Wall Charger; G4 Receiver USBCable | PASS |

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Biocompatibility: Biocompatibility testing was performed on the sterile components of the System, including the Sensor Applicator, Sensor Probe, and Sensor pod as well as the Transmitter. Biocompatibility testing was conducted in accordance with ISO 10993-1. The following table (Table 2) includes a description of the testing performed and the results.

Table 2. G4 Platinum System Biocompatibility Results

| Test | Result |
| --- | --- |
| Cytotoxicity (MEM Elution) | Non-toxic |
| Sensitization | No evidence of sensitization |
| Intracutaneous Reactivity | Non-irritant |
| Acute Systemic Toxicity (Acute Systemic Injection Test) | Non-toxic |
| Systemic Toxicity (Material Mediated Pyrogen) | Non-pyrogenic |
| Subchronic Toxicity (30 day) | Non-toxic |
| Genotoxicity (Ames Test) | Non-mutagenic |
| Genotoxicity (Chromosome Aberration) | Non-genotoxic |
| Genotoxicity (Mouse Micronucleus) | Non-mutagenic |
| Muscle Implantation | Non-irritant |

Sterility Assurance: Sterilization of the System components (applicator, transmitter housing/base, insertion needle, Sensor) utilized electron beam radiation using the $\mathrm{VD}_{\mathrm{max}}^{25}$ method. The minimum exposure dose required to sterilize the product with a sterility assurance level of 10-6 is $25.0\mathrm{kGy}$. Transmitters and Receivers are not sterile products.

To validate the sterilization process, the procedure for method $\mathrm{VD}_{\mathrm{max}}^{25}$ for multiple production batches outlined in ANSI/AAMI/ISO 11137-2:2006 was followed. In order to determine the sterilization dose, a bioburden recovery method test was initially performed, followed by the determination of the bioburden recovery factor. The average bioburden was determined for three production lots. The total overall average bioburden was then calculated using the recovery factor and was used to obtain the $\mathrm{VD}_{\mathrm{max}}^{25}$ dose. A verification dose experiment was then performed using 10

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samples from one production lot. Each sample was individually subjected to a test of sterility. Since there was no more than one positive test of sterility from the 10 tests carried out, 25 kGy was substantiated as the minimum sterilization dose. Dose mapping was also performed at 25 kGy using the final product packaging to confirm proper irradiation.

**Electromagnetic Compatibility and Interference:** Acceptable electromagnetic compatibility (EMC) and electromagnetic immunity (EMI) testing was performed for the G4 Platinum Transmitter and G4 Platinum Receiver. Criteria used in the testing included the following occurrences that were correlated to the disturbance: device turning on or off, changing modes, resetting, no longer functioning, the device becoming unreadable for more than 5 seconds, the device changing settings, alarm failures, power supply ceases to source +5VDC4 for more than 5 seconds, packets are dropped at a rate of no more than 1 out of 205 consecutive transmissions (95% success), EGV Value is outside of the +/- 5mg/dL or +/- 5% (whichever is greater) of the starting baseline value for more than one consecutive packet (radiated RF immunity testing only), Receiver database is erased, Receiver date or time is changed (other than normal time progression), Transmitter ID is changed (in receiver), Low Glucose Alarm ceases to annunciate, the raw count during manufacturing test mode deviates more than +/- 5% of the baseline counts (radiated RF immunity testing only), the system fails the functional test after EMC testing.

Radiofrequency (RF) communication testing was performed demonstrating compliance with Federal Communications Commission standards (Title 47 Part 15). Radiated Emissions Test, Occupied Bandwidth, and Band-edge Measurement testing was performed.

Radiofrequency wireless testing, including wireless co-existence, was conducted on the System. Testing indicated that the System can operate in the presence of RF interference and co-exists with other wireless devices operating in the same vicinity. Other wireless testing successfully verified the performance of the RF transmission intervals, RF frequency intervals, RF carrier frequency, and listen before talk testing. The communication distance of 20 feet was verified and successful RF communication occurred when worn in different locations and orientations on a human torso model.

**Shelf-life and Storage Stability:** Real-time studies were conducted to examine the effect of aging on the sterilized Sensors and to determine an appropriate shelf life for sensors stored at ambient conditions. The in-vitro Sensor performance and product functionality data collected from this study was used in the determination of appropriate shelf-life for Sensors and applicators. Testing included: deployment testing, seal integrity testing, contact resistance testing, reference electrode capacity testing, Sensor pouch seal strength test, Sensor pouch bubble leak test, shelf-life sensor performance. Shelf-life testing was provided to support the 6 month Sensor shelf-life. The labeling instructs the user to store the Sensors at 36°F to 77°F and

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between 15% and 85% relative humidity and indicates that the Sensors should not be stored in the freezer.

Adequate testing was performed to support a shelf-life for the Transmitter battery (which translates to the Transmitter shelf-life) of 8 months and a normal operating battery/Transmitter life of 6 months. The Transmitters and Receivers should be stored at 32°F to 113°F, between 15% and 85% relative humidity.

**Packaging Integrity/Shipping Testing:** The packaging consists of a Receiver kit, a Transmitter kit, and a Sensor kit that may contain a single Sensor or a 4-pack. The units are placed in a box for shipment in the US. Testing was performed per ISTA 2A 2008 guidelines using samples with representative shipping configurations comprised of the Sensor, Transmitter, and Receiver kits. The packaged samples were subjected to atmospheric conditioning, vibration, compression and drop tests and the structural integrity of the packaging, and pouch seal examined. The individual components, i.e., Sensor, Transmitter, and Receiver met the functional performance requirements per protocol at 95% confidence/90% Reliability. The results passed demonstrating that the G4 Platinum System packaging met the applicable requirements per product specifications.

The microbial barrier properties of the material used in the manufacture of the sterile Sensor pouch was evaluated according to ASTM F1608. Results demonstrated that the material met the applicable requirements per product specifications.

**Software Validation:** Testing was performed to ensure the performance of each of the manufactured devices has met the software design specification and software requirements specifications established for each item. The verification and validation activities are completed according to the FDA guidance entitled General Principles of Software Validation: Final Guidance for Industry and FDA Staff released January 11, 2002.

Software validation was provided for the software programs for the Receiver, the Transmitter, and the Studio Software (the program to allow the user or healthcare provider to download results from the Receiver to a PC to view the data and trends).

Verification and validation of the software implementation was accomplished through software code reviews, unit testing, and integration testing. These evaluations verify that the software implementation satisfies the design implementation as defined in the Software Requirements Specifications and validate that the software conforms to user needs and intended uses.

**Human Factors and Usability Testing:** Usability testing (user-interface design validation) of the System was performed following the Draft Guidance for Industry and FDA staff titled, *Applying Human Factors and Usability Engineering to Optimize Medical Device Design*, dated June 22, 2011. The testing considered device users, use environment, and user interfaces including device labeling and

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training. The summative study involved simulated use of the CGM system with 30 participants with differing levels of CGM experience and diabetes therapy that were presented with a series of realistic CGM use scenarios and asked for their response. The study was intended to collect both observational and qualitative data. It was also designed to assess the adequacy of the user instructions and training materials to support safe and effective use of the device.

## B. Animal Studies

No animal studies were conducted using the Dexcom G4 Platinum CGM System.

## C. Additional Studies

None

## X. SUMMARY OF PRIMARY CLINICAL STUDY

The applicant performed a pivotal clinical study to establish a reasonable assurance of safety and effectiveness with the Dexcom G4 Platinum System for detecting trends and tracking patterns when used as an adjuvant to blood glucose testing in subjects with diabetes mellitus. This study was performed in the US under IDE #G110107/S001. Data from this clinical study were the basis for the PMA approval decision. A summary of the clinical study is presented below.

### A. Study Design

Subjects were enrolled between December 9, 2011 and February 10, 2012. The database for this PMA reflected data collected through February 10, 2012 and included enrolling 72 patients. There were 4 investigational sites.

The purpose of the pivotal study was to evaluate the safety and effectiveness of the G4 Platinum System when used as an adjuvant to blood glucose testing over a 7-day period in subjects &gt;18 years-old with diabetes mellitus. The study was an open-label, non-randomized, single-arm, multi-center, pivotal study.

The 72 enrolled subjects wore the G4 Sensor for one week (168 hours) and participated in both an in-clinic and a home use portion of the study. Subjects were instructed to use CGM information as an adjunct to (not a replacement for) using standard self-monitoring blood glucose (SMBG) meters for the self-management of diabetes. After being provided instructional materials, subjects inserted the sensor themselves.

One hundred and eight (108) Transmitters and 108 Receivers were used with no replacements needed. One hundred twenty-one (121) Sensors were inserted, 13 (11%) of which were replacements. Sensors were replaced primarily due to mechanical failures (e.g. sensor wire not attached to pod or sensor attached to adhesive) or user errors (e.g. improper insertion technique).

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# In-Clinic Portion of the Study

The primary objective was to characterize the System performance with respect to laboratory reference measurements on venous blood samples for all study subjects (there was no separate control group). The device performance was primarily evaluated in terms of point and rate accuracy of the System in comparison to a clinical laboratory reference method, the Yellow Springs Instrument 2300 STAT Plus Glucose Analyzer (YSI). The evaluation of safety and effectiveness involved the assessment of many analyses of the data generated during the study (see Tables 5 to 17; Section X.D.2); however, the criteria used by the sponsor to assess point accuracy was the proportion of System readings that were within ±20% of the YSI reference value for glucose levels &gt;80 mg/dL and within ±20 mg/dL for YSI glucose levels &lt;80 mg/dL. The trend accuracy of the device performance was evaluated, as well as the temporal System accuracy at different glucose rates of change and different glucose ranges (hypoglycemic, euglycemic, and hyperglycemic ranges).

The performance of the System was determined across the 7 days of wear time. All subjects were asked to come into the clinic on Day 1, 4, and 7 for a 12-13 hour in-clinic session. To obtain primary matched paired measurements subjects had venous blood drawn from an intravenous catheter approximately once every 15 +/- 5 minutes to allow for frequent comparison of the System to YSI. The YSI measurements were made on plasma samples obtained from the collected venous samples. Readings from the System were reported every 5 minutes and paired with YSI values in order to characterize the agreement between the System and YSI.

During the in-clinic sessions the study investigators were blinded to the G4 sensor results and all treatment decisions were based on the reference glucose readings (YSI). All subjects were also asked to take two fingerstick measurements per hour using the provided SMBG meter (LifeScan OneTouch Ultra2) and additionally as indicated for diabetes management or clinical safety purposes.

During the in-clinic portion of the study the glucose levels of certain subjects were deliberately manipulated (with close observation by the study investigator staff) to induce high or low blood glucose via carbohydrate consumption, insulin dosing, and exercise to achieve YSI sample measurements within target glucose bins following a protocol specific guideline. This manipulation was included in the study design to allow the collection of comparison data at glucose concentrations that spanned the claimed measuring range of the System (40-400 mg/dL).

Sensors were calibrated approximately once every 12 hours, using the SMBG meter values obtained from the LifeScan OneTouch Ultra2 meter. Throughout the 7-day wear period, the Sensor was calibrated with an average of 2 fingersticks per day (approximately once every 12 hours).

Precision of the System was assessed on a subset of patients (36 subjects from two of the clinical sites) wearing two Systems simultaneously. One of each of the paired systems was blinded (CGM values, trends, alerts/alarms not provided) and the other was unblinded during home use. Subjects manually entered fingerstick measurement

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values for calibration into both G4 Platinum Receivers and were instructed to enter the same calibration values to both Receivers at the same time (one immediately after the other). The blinded CGM system was only used to evaluate device precision, the unblinded CGM system was considered the primary CGM system for device performance in comparison to the laboratory reference YSI.

Precision of the System was assessed and measured by the average absolute percent difference estimates and percent coefficient of variations comparing data from the two simultaneously worn sensors.

## Home Portion of the Study

The remainder of the study, time between the in-clinic sessions, took place at home. During home use, subjects performed two SMBG fingerstick measurements per day required for calibration of the system and additional fingerstick measurements as required for their diabetes management. Subjects were required to use the blood glucose meter provided to them (LifeScan OneTouch Ultra2) for all SMBG measurements obtained during the 7-day wear period. All subjects were instructed to manage their glucose levels per their routine diabetes management guidelines during home use.

## Summary of Statistical Methods

Summary statistics for continuous variables include the mean, standard deviation, median, and range. All enrolled subjects who underwent device insertion were included in all analyses. The hypothesis test was conducted using a 1-sided binomial test, and a 95% confidence interval of the true percentage of paired points meeting the pre-specified accuracy criteria. These criteria, used by the sponsor, were met if the G4 measurement paired with a YSI measurement below 80 mg/dL is within 20 mg/dL of that YSI measurement. A G4 measurement paired with a YSI measurement above 80 mg/dL is considered accurate if it is within 20% of that YSI measurement. Normal approximated and bootstrapped confidence intervals were presented for the agreement proportion.

In subjects wearing two sensors concurrently, only the unblinded G4 Sensor was included in the primary efficacy endpoint analysis.

From the seventy-two (72) subjects enrolled in the study, a total of 9555 Sensor-YSI matched pairs were collected for the primary analysis. Among these data there were a total of 9093 matched pairs with both YSI and G4 CGM measurements within the System measurement range of 40 to 400 mg/dL. The study collected sufficient number of samples to satisfy the above described sample size requirements and hypothesis tests. With the observed proportion of interest of the study sample, the actual sample size provided more than 90% power for the hypothesis test.

## Key Secondary endpoints

- Mean and Median Absolute Relative Differences from YSI
- Hypoglycemia and Hyperglycemia Detection Rates
- Hypoglycemia and Hyperglycemia missed detection rates

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- True Alert Rate
- False Alert Rate
- Accuracy of glucose rate of change of Sensor compared to glucose rate of change of YSI

1. Clinical Inclusion and Exclusion Criteria

Enrollment in the study was limited to patients who met the following inclusion criteria:

a. Age 18 years or older
b. Diagnosed with diabetes mellitus
c. Used one of the following methods for their diabetes management: a) intensive insulin therapy (IIT) with defined insulin:carbohydrate ratios and glucose correction factors; or b) non-intensive insulin therapy (non-IIT)
d. For insulin-using subjects only – would not inject insulin or wear an insulin pump insertion set within 3 inches from the Sensor site during sensor wear
e. Would insert Sensor(s) on their own and if asked, willing to wear 2 systems simultaneously
f. Would use only the blood glucose meter provided for all blood glucose measurements performed during Sensor wear and not allow others to use this meter during the study
g. Would participate in three 12-13 hour in-clinic sessions during which subjects must be willing to take 2 fingerstick measurements per hour (and additionally as indicated for diabetes management or clinical safety purposes)
h. Would have an intravenous catheter inserted for 4 blood draws per hour over a total of 12-13 hours for each of the 3 in-clinic sessions
i. For intensive-insulin using (IIT) subjects only – During each in-clinic session, would have their blood glucose levels manipulated into high and low glucose levels via carbohydrate consumption, meal timing, activity levels, and/or insulin dosing. (Subjects not on IIT will only be observed during each in-clinic session. These subjects would not participate in the deliberate insulin and glucose challenges and will manage their diabetes as they usually do)
j. For subjects that exercise routinely (at least 3 times per week), would exercise for 20 to 30 minutes during each in-clinic session, if asked
k. Would take a minimum of 7 fingerstick measurements per day during home use days (required fingerstick measurements for calibration purposes, additional for confirmatory/comparative purposes) with the meter provided
l. Would refrain from the use of acetaminophen during Sensor wear period and the day prior to Sensor insertion
m. Able to speak, read, and write English
n. In the investigator’s opinion, able to be compliant with provisions laid out in this protocol.

Patients were not permitted to enroll in the study if they met any of the following exclusion criteria:

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a. Have extensive skin changes/diseases that preclude wearing the required number of devices on normal skin (e.g., extensive psoriasis, recent burns or severe sunburn, extensive eczema, extensive scarring, extensive tattoos, dermatitis herpetiformis) at the proposed wear sites
b. Have a known allergy to medical-grade adhesives
c. Are pregnant, as demonstrated by a positive pregnancy test within 72 hours of Sensor insertion
d. Were on active dialysis
e. Had a hematocrit level that is less than 36% or greater than 55% at screening visit
f. Were participating in another investigational study protocol (e.g, if a subject has recently completed participation in another drug study, the subject must have completed that study at least 30 days prior to being enrolled in this study)
g. Had a history of cardiovascular disease (including, but not limited to, ischemic heart disease, peripheral vascular disease, cardiomyopathy, cerebrovascular disease, congenital heart disease, or significant arrhythmias), epilepsy, severe migraines in the past 6 months, adrenal disease, syncope, significant hypoglycemia unawareness, or a history of severe hypoglycemia (requiring emergency medical intervention) within the last 6 months
h. Had any chronic infectious disease or intercurrent illness that would interfere with their participation in the study or pose an excessive risk to study staff handling venous or capillary blood samples (e.g. HIV/AIDS, Hepatitis B or C)
i. Had a MRI scan, CT scan, or diathermy scheduled during the week of the study. If any of these procedures are required urgently during the study, subjects would notify the study staff, end their CGM session, and remove their Sensor.

## 2. Follow-up Schedule

At the end of the Sensor wear period (168 hours), subjects removed the Systems according to User’s Guide instructions and/or training materials provided. Upon removal, all the Sensor insertion sites were examined and evaluated by the study staff. Sensors were visually inspected at the site. All used and unused Systems (including Sensor, Transmitter, and Receiver) were returned by study staff to Dexcom for examination (e.g. close examination for mechanical integrity of Sensor wires). Study investigators documented any Adverse Device Effects (including irritations) and evaluated safety issues related to system use during the study. No long-term follow up was included in this study protocol.

## 3. Clinical Endpoints

The primary effectiveness measurements for this study were the glucose measurements from the Dexcom G4 Platinum System and the blood glucose values measured by the YSI Analyzer during in-clinic sessions. The sponsor

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defined criteria of G4 System performance was assessed as the percentage of paired points with absolute differences between G4 System results and YSI blood glucose results of ≤20 mg/dL (for YSI values ≤80 mg/dL), or with absolute relative differences of ≤20% (for YSI values &gt;80 mg/dL).

The primary endpoint depended on the G4-YSI matched pairs that were obtained in the in-clinic sessions on days 1, 4, and 7. Subjects contributed anywhere from 6 to 150 pairs with 85% of them contributing at least 130 pairs.

Safety data of the System were also collected and characterized by the incidence and severity of Adverse Device Effects, Serious Adverse Device Events, and Unanticipated Adverse Device Effects experienced by study subjects.

## B. Accountability of PMA Cohort

All 72 subjects enrolled into the study participated in the in-clinic and the home portions of the study. All enrolled subjects contributed at least one matched pair of sensor/YSI observations to the efficacy data. 66 subjects attended all three in-clinic sessions.

## C. Study Population Demographics and Baseline Parameters

The demographics of the study population are typical for a continuous glucose monitoring system study performed in the US. See the following tables (Tables 3A and 3B) for a description of the demographics and baseline characteristics of the study population.

Table 3A. Subject Demographics

| Category | Number of Subjects Enrolled (N=72) |
| --- | --- |
| Gender, N (%) | |
| Male | 44 (61.1%) |
| Female | 28 (38.9%) |
| Age (years) | |
| Mean | 42.20 |
| SD | 13.95 |
| Range | 18.3-74.0 |
| Race | |
| White | 68 (94.4%) |
| Asian | 1 (1.4%) |
| Black, African American, or of African Heritage | 3 (4.2%) |
| Ethnicity | |
| Hispanic or Latino | 8 (11.1%) |
| Not Hispanic or Latino | |
| Body Mass Index | |

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| Mean | 28.66 |
| --- | --- |
| SD | 5.78 |
| Range | 19.6 - 49.4 |

Table 3B. Subject Baseline Parameters

| Type of Diabetes at Diagnosis | |
| --- | --- |
| Type I | 60 (83.3%) |
| Type II | 12 (16.7%) |
| Diabetes Duration (years) | |
| Mean | 18.9 |
| SD | 11.9 |
| Range | 1 - 55 |
| Body Mass Index | |
| Mean | 28.66 |
| SD | 5.78 |
| Range | 19.6 - 49.4 |
| Baseline A1c (%) | |
| Mean | 7.70 |
| SD | 1.30 |
| Range | 5.5 - 10.7 |

## D. Safety and Effectiveness Results

### 1. Safety Results

The analysis of safety was based on the 72 subjects that participated in the study. The safety data of the System were assessed by evaluation of the incidence of all Adverse Device Effects (ADEs), Serious Adverse Device Events (SADEs), and Unanticipated Adverse Device Effects (UADEs) experienced by study subjects. Adverse events (AEs) were listed in terms of severity and relationship to device. Sensor insertion site and adhesive area were examined for erythema, edema and infection. The local skin reactions from the insertion site or the adhesive were evaluated quantitatively using Draize18 classifications.

#### Adverse effects that occurred in the PMA clinical study:

A total of 38 Adverse Events (AEs) were reported during the study. Twenty-two of the AEs were deemed related to the device due to Sensor insertion and adhesive area irritations; all these AEs were deemed mild and were resolved or stable upon study completion.

These events included all skin irritations. Irritation resulting from use of the System Sensor was tabulated at each Sensor removal and categorized by needle insertion site and adhesive area. Any bruising, edema, and erythema observed at each area were evaluated according to Draize’s scale. The following table (Table 4) summarizes the quantitative assessments (Draize’s scales) of Sensor insertion and adhesive area reactions:

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Table 4 Adverse Events.

| AE | N (%) |
| --- | --- |
| Sensor Site Erythema | |
| Very Slightly | 7 (5.8%) |
| | |
| Adhesive area Erythema | |
| Very Slightly | 12 (9.9%) |
| | |
| Adhesive area Edema | |
| Very Slightly | 3 (2.5%) |

The following sixteen (16) other reported AEs were deemed not related to the devices: 7 mild headaches; 1 moderate headache; 1 case of a mild sore throat; 1 subject had a skin biopsy (mild) on the face to rule out skin cancer; 1 case of mild vomiting after drinking Boost (nutritional drink given during the study); 1 case of erythema @ needle insertion site; 1 case of mild emesis; 1 case of mild viral syndrome; 1 case of moderate atypical chest pain; 1 case of moderate pericarditis.

All AEs were resolved or stable at study termination.

Per protocol, the mechanical integrity of each Sensor was independently assessed after removal of the Sensor from the subcutaneous adipose tissue. There were no reports of broken Sensor wires.

No infections occurred at either insertion or adhesive areas.

No Serious Adverse Device Events (SADEs) or Unanticipated Adverse Device Effects (UADEs) occurred during the study.

## 2. Effectiveness Results

The primary effectiveness measurements for this study were based on the performance evaluation of the Dexcom G4 Platinum System compared to the blood glucose values measured by YSI during in-clinic sessions. Key effectiveness outcomes are presented in the following tables (Tables 5 to 17).

### Agreement of System Results with Reference Readings (YSI):

Agreement between the System and blood glucose values is characterized using paired System and YSI values. The System and YSI results were compared by pairing the YSI blood glucose value to a System glucose reading that occurred immediately after the YSI was collected. The agreement of the System to blood glucose value was assessed by calculating the percentage of System readings that were within 15%, 20%, 30%, 40% and greater than 40% of the YSI values.

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The total number of data pairs considered in this analysis was 9152. A total of 9555 Sensor-YSI matched pairs were collected in this study; however, this analysis included CGM readings that were within the measuring range of the System (40-400 mg/dL). Of these, eighty-two percent (82%) of the System readings fall within ±20 mg/dL (1.1 mmol/L) of the YSI blood glucose values (&lt; 80 mg/dL or 4.4 mmol/L) and within ±20% of YSI blood glucose values (≥ 80 mg/dL or 4.4 mmol/L). The confidence interval (CI) used by the sponsor was considered to be the proportion of paired values meeting the 20/20 criteria (System readings falling within ±20 mg/dL of YSI for samples &lt; 80 mg/dL glucose and within ±20% of YSI for sample ≥ 80 mg/dL glucose) which was estimated to be 82% with a CI of (78.4, 84.7).

For readings less than or equal to 80 mg/dL (4.4 mmol/L) glucose the absolute difference in mg/dL (mmol/L) between the two glucose results was calculated. For values greater than 80 mg/dL (4.4 mmol/L) the absolute percent difference (%) from the YSI values was calculated. The percentages of total readings within 15 mg/dL (0.8 mmol/L) or 15%, 20 mg/dL (1.1 mmol/L) or 20%, 30 mg/dL (1.7 mmol/L) or 30%, 40 mg/dL (2.2 mmol/L) or 40% or greater than 40 mg/dL (2.2 mmol/L) or 40% were then calculated in Table 5-A and Table 5-B.

*System Agreement to YSI within CGM Glucose Ranges*: Table 5-A below is categorized within CGM glucose concentrations (first column) and outlines how often a reading on the CGM matched the YSI blood glucose reading.

**Table 5-A. System Agreement to YSI within CGM Glucose Ranges**

| CGM Glucose Range mg/dL (mmol/L) | Number of paired System-YSI | Percent within 15/15% YSI | Percent within 20/20% YSI | Percent within 30/30% YSI | Percent within 40/40% YSI | Percent Greater than 40/40% YSI |
| --- | --- | --- | --- | --- | --- | --- |
| Overall | 9152 | 71% | 82% | 92% | 97% | 3% |
| 40-60 (2.2-3.3) | 512 | 67% | 78% | 88% | 94% | 6% |
| 61-80 (3.4-4.4) | 781 | 73% | 85% | 94% | 98% | 2% |
| 81-180 (4.5-10.0) | 3853 | 67% | 78% | 91% | 97% | 3% |
| 181-300 (10.1-16.7) | 2784 | 72% | 84% | 93% | 96% | 4% |
| 301-350 (16.7-19.4) | 775 | 82% | 91% | 97% | 98% | 2% |
| 351-400 (19.4-22.2) | 447 | 74% | 84% | 91% | 95% | 5% |

Note: CGM readings are within 40-400 mg/dL (2.2-22.2 mmol/L).

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System Agreement to YSI within YSI Glucose Ranges: Table 5-B below is categorized within YSI reference value ranges (first column) and outlines how often a CGM reading matched with the YSI blood glucose level bins.

During the clinical study, the reference YSI values outside of the System measurable range were collected. Among these samples, on 22 occasions, when the actual blood glucose concentrations (as determined by the YSI analyzer) were lower than 40 mg/dL (2.2 mmol/L), 73% of the paired CGM glucose readings were within 20 mg/dL (1.1 mmol/L) of the YSI values, and 86% of the paired CGM glucose readings were within 30 mg/dL (1.7 mmol/L) of the YSI values. On 37 occasions, when the actual blood glucose concentration (as determined by the YSI analyzer) were greater than 400 mg/dL (22.2 mmol/L), 86% of paired System readings were within 20% of the YSI values, and 100% of the paired CGM glucose readings were within 30% of the YSI values.

Table 5-B. System Agreement to YSI within YSI Glucose Ranges

| YSI Glucose Range mg/dL (mmol/L) | Number of paired System-YSI | Percent within 15/15% YSI | Percent within 20/% 20 YSI | Percent within 30/% 30 YSI | Percent within 40/% 40 YSI | Percent Greater than 40/% 40 YSI |
| --- | --- | --- | --- | --- | --- | --- |
| Overall | 9152 | 71% | 82% | 92% | 97% | 3% |
| <40 (2.2) | 22 | 59% | 73% | 86% | 100% | 0% |
| 40-60 (2.2-3.3) | 461 | 75% | 87% | 94% | 98% | 2% |
| 61-80 (3.4-4.4) | 890 | 69% | 81% | 94% | 98% | 2% |
| 81-180 (4.5-10.0) | 3892 | 65% | 76% | 88% | 95% | 5% |
| 181-300 (10.1-16.7) | 2644 | 74% | 85% | 94% | 97% | 3% |
| 301-350 (16.7-19.4) | 869 | 79% | 92% | 99% | 100% | 0% |
| 351-400 (19.4-22.2) | 337 | 84% | 91% | 98% | 100% | 0% |
| >400 (22.2) | 37 | 86% | 86% | 100% | 100% | 0% |

Note: CGM readings are within 40-400 mg/dL (2.2-22.2 mmol/L).

Agreement of CGM to YSI When CGM Reads 'Low' or 'High':
The System reports glucose concentrations between 40 and 400 mg/dL (2.2-22.2 mmol/L). When the System determines the glucose level is below 40 mg/dL (2.2

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mmol/L), the Receiver displays “LOW” in Status Box. When the G4 System determines that the glucose level is above 400 mg/dL (22.2 mmol/L), the Receiver displays “HIGH” in the Status Box. Because the System does not display glucose values below 40 mg/dL (2.2 mmol/L) or above 400 mg/dL (22.2 mmol/L), the comparisons to the actual blood glucose concentrations (as determined by the YSI analyzer) when CGM is classified as “LOW” or “HIGH” are included separately in the following table (Table 6). The table includes the numbers and the cumulative percentages when YSI values were less than certain glucose levels (for ‘LOW’), and when YSI values were greater than certain glucose levels (for ‘HIGH’).

Table 6. Number and Percentage of YSI values when CGM readings are ‘LOW’ or ‘HIGH’.

| YSI mg/dL (mmol/L) | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| CGM Readings | CGM-YSI pairs | <55 (3.1) | <60 (3.3) | <70 (3.9) | <80 (4.4) | >80 (4.4) | Total |
| ‘LOW’ | n | 66 | 18 | 39 | 19 | 13 | 155 |
| | Cumulative % | 42% | 54% | 79% | 92% | 8% | |
| YSI mg/dL (mmol/L) | | | | | | | |
| CGM Readings | CGM-YSI pairs | >340 (18.9) | >320 (17.8) | >280 (15.6) | >240 (13.3) | <240 (13.3) | Total |
| ‘HIGH’ | n | 189 | 31 | 18 | 8 | 2 | 248 |
| | Cumulative % | 76% | 89% | 96% | 99% | 41% | |

Concurrence of System and Laboratory Reference Values:

The percentage of concurring CGM readings and YSI reference values were included in Table 7. This table is categorized by each CGM glucose range (first column) and describes for each range of CGM glucose readings, what percentage of paired YSI values were in the same glucose range (shaded) or in glucose ranges above and below the paired CGM readings.

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Table 7. Concurrence of System Readings and YSI values.

| CGM-mg/dL (mmol/L) | Number of Paired CGM-YSI | Percent of matched pairs in each YSI glucose range for each Sensor glucose range | | | | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | <40 (<2.2) | 40-60 (2.2-3.3) | 61-80 (3.4-4.4) | 81-120 (4.4-6.7) | 121-160 (6.7-8.9) | 161-200 (8.9-11.1) | 201-250 (11.1-13.9) | 251-300 (13.9-16.7) | 301-350 (16.7-19.4) | 351-400 (19.4-22.2) | >400 (>22.2) |
| <40 (<2.2) | 155 | 6% | 48% | 37% | 7% | 1% | 0% | 0% | 0% | 0% | 0% | 0% |
| 40-60 (2.2-3.3) | 512 | 4% | 49% | 36% | 11% | 1% | 0% | 0% | 0% | 0% | 0% | 0% |
| 61-80 (3.4-4.4) | 781 | 0% | 22% | 51% | 24% | 1% | 0% | 0% | 0% | 0% | 0% | 0% |
| 81-120 (4.4-6.7) | 1706 | 0% | 2% | 17% | 66% | 13% | 1% | 0% | 0% | 0% | 0% | 0% |
| 121-160 (6.7-8.9) | 1492 | 0% | 0% | 1% | 25% | 60% | 13% | 2% | 0% | 0% | 0% | 0% |
| 161-200 (8.9-11.1) | 1240 | 0% | 0% | 0% | 2% | 28% | 53% | 16% | 2% | 0% | 0% | 0% |
| 201-250 (11.1-13.9) | 1181 | 0% | 0% | 0% | 0% | 3% | 21% | 51% | 21% | 3% | 1% | 0% |
| 251-300 (13.9-16.7) | 1018 | 0% | 0% | 0% | 0% | 0% | 4% | 19% | 49% | 24% | 3% | 0% |
| 301-350 (16.7-19.4) | 775 | 0% | 0% | 0% | 0% | 0% | 0% | 3% | 28% | 51% | 16% | 1% |
| 351-400 (19.4-22.2) | 447 | 0% | 0% | 0% | 0% | 0% | 0% | 3% | 10% | 43% | 38% | 7% |
| >400 (>22.2) | 248 | 0% | 0% | 0% | 0% | 0% | 0% | 1% | 6% | 21% | 57% | 15% |

## Evaluation of Accuracy:

Accuracy between matched pairs was also estimated by calculating the percent difference between the System reading and the YSI value. The System and YSI values were compared by pairing the System reading that fell immediately after the YSI value was collected.

The mean percent difference is the average of all positive and negative percent differences between the two devices and demonstrates whether the System reads higher or lower on average than the YSI at each glucose range.

Another estimate used to evaluate the accuracy of the System is the absolute percent difference. The absolute percent difference provides the percent

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difference or “distance” between the System and YSI values, but does not demonstrate whether the System is reading, on average, higher or lower than the YSI laboratory standard. The mean absolute percent difference is the average “distance” (regardless if positive or negative) between System readings and YSI values.

These accuracy measures in differences were based on 9152 paired glucose results and are summarized in the following tables (Table 8-A and Table 8-B).

Table 8-A below is categorized by CGM glucose range (first column) and demonstrated that the System read, on average, 2.9% different (Mean Percent Difference) than the reference and 13.3% absolute different (Mean Absolute Difference) than the reference values.

Table 8-A. System Difference to YSI within CGM Glucose Ranges.

| CGM Glucose Ranges mg/dL (mmol/L) | # of Paired System YSI | Mean Percent Difference (%) | Median Percent Difference (%) | Mean Absolute Percent Difference (%) | Median Absolute Percent Difference (%) |
| --- | --- | --- | --- | --- | --- |
| Overall | 9152 | 2.9 | 1.7 | 13.3 | 9.8 |
| 40-60
(2.2-3.3) | 512 | -10.0
(-0.6) | -8.2
(-0.5) | 13.5
(0.8) | 9.7
(0.5) |
| 61-80
(3.4-4.4) | 781 | -2.4
(-0.1) | -0.4
(0.0) | 11.4
(0.6) | 8.6
(0.5) |
| 81-180
(4.5-10.0) | 3853 | 4.8 | 3.0 | 13.8 | 9.8 |
| 181-300
(10.1-16.7) | 2784 | 2.1 | 0.0 | 11.9 | 9.2 |
| 301-350
(16.7-19.4) | 775 | 3.8 | 2.8 | 9.8 | 7.9 |
| 351-400
(19.4-22.2) | 447 | 10.4 | 7.7 | 12.8 | 9.1 |

* For CGM ≤ 80 mg/dL (4.4 mmol/L), the differences in mg/dL (mmol/L) are included instead of percent differences (%). Note: CGM readings are within 40 to 400 mg/dL (2.2-22.2 mmol/L), inclusive.

Table 8-B below is categorized within YSI glucose value ranges (first column) and demonstrated that the Median Percent Difference shows that half of the time the System read 1.7% or less than the YSI blood glucose values and the Median Absolute Percent Difference shows that half of the time the System read about 9.8% or less different than YSI blood glucose values.

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Table 8-B. System Difference to YSI within YSI Glucose Ranges.

| YSI Glucose Ranges mg/dL (mmol/L) | # of Paired System YSI | Mean Percent Difference (%) | Median Percent Difference (%) | Mean Absolute Percent Difference (%) | Median Absolute Percent Difference (%) |
| --- | --- | --- | --- | --- | --- |
| Overall | 9152 | 2.6 | 1.7 | 13.3 | 9.8 |
| *<40
(2.2) | 22 | 14.4
(0.8) | 12.9
(0.7) | 14.4
(0.8) | 12.9
(0.7) |
| 40-60
(2.2-3.3)* | 461 | 7.3
(0.4) | 6.3
(0.4) | 11.1
(0.6) | 8.8
(0.5) |
| 61-80
(3.4-4.4)* | 890 | 3.6
(0.2) | 2.4
(0.1) | 12.2
(0.7) | 10.2
(0.6) |
| 81-180
(4.5-10.0) | 3892 | 3.8 | 3.0 | 14.0 | 10.1 |
| 181-300
(10.1-16.7) | 2644 | 1.3 | 0.3 | 11.2 | 8.5 |
| 301-350
(16.7-19.4) | 869 | -1.7 | -1.5 | 9.8 | 8.6 |
| 351-400
(19.4-22.2) | 337 | -5.8 | -5.2 | 8.8 | 6.8 |
| >400
(22.2) | 37 | -11 | -10 | 11.2 | 10.3 |

For CGM ≤ 80 mg/dL (4.4 mmol/L), the differences in mg/dL (mmol/L) are included instead of percent differences (%). Note: CGM readings are within 40 to 400 mg/dL (2.2-22.2 mmol/L).

Low and High Glucose Alerts: The System has programmable High and Low Glucose Alerts that can be changed by the user and a non-changeable Low Glucose Alarm set at 55 mg/dL. The labeling instructs the user to consult with their doctor to determine what alert settings would be best for them.

To assess the ability of the System to detect high and low glucose levels System results were compared to YSI results at low and high blood glucose levels and it was determined if the alert may have sounded. The System and YSI readings were compared by pairing the System reading that occurred immediately after the YSI reading was collected. There were 9555 paired System and YSI results evaluated.

Low Glucose Alert: Estimates of how well the adjustable Low Glucose Alert performed are presented below in Table 9 followed by the definitions of the terms used in the tables.

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Table 9. Hypoglycemic Alert Evaluation.

| Alert Level
mg/dL
(mmol/L) | True Alert Rate | False Alert Rate | Hypoglycemia Detection Rate | Hypoglycemia Missed Detection Rate |
| --- | --- | --- | --- | --- |
| 55 (3.1) | 50% | 50% | 71% | 29% |
| 60 (3.3) | 64% | 36% | 75% | 25% |
| 70 (3.9) | 79% | 21% | 83% | 17% |
| 80 (4.4) | 87% | 13% | 86% | 14% |
| 90 (5.0) | 90% | 10% | 89% | 11% |

Hypoglycemia Alert Rate:

The Alert Rate shows how often the alert was right or wrong. The True Alert Rate is the % of time the device alarmed when the blood glucose level was at or below the alert setting within 15 minutes before or after the device alarmed. The False Alert Rate is the % of time the device alarmed when the blood glucose level was above the alert setting within 15 minutes before or after the device alarmed.

Hypoglycemia Detection Rate:

The Detection Rate shows how often the device recognized and alerted that there was an episode of hypoglycemia or how often it missed such an event. The Hypoglycemia Detection Rate is the % of time the blood glucose level was at or below the alert setting and device alarmed within 15 minutes before or after the blood glucose was at or below the alert settings. The Hypoglycemia Missed Detection Rate is the % of time the blood glucose was at or below the alert setting, but the device did not alarm within 15 minutes before or after the blood glucose was at or below the alert setting.

High Glucose Alert: Estimates of how well the adjustable High Glucose Alert performed are presented in the table (Table 10) followed by the definitions of the terms used in the tables:

Table 10. Hyperglycemic Alert Evaluation.

| Alert Setting
mg/dL
(mmol/L) | True Alert Rate | False Alert Rate | Hyperglycemia Detection Rate | Hyperglycemia Missed Detection Rate |
| --- | --- | --- | --- | --- |
| 120 (6.7) | 95% | 5% | 98% | 2% |
| 140 (7.8) | 94% | 6% | 97% | 3% |
| 180 (10.0) | 92% | 8% | 97% | 3% |
| 200 (11.1) | 92% | 8% | 97% | 3% |

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| Alert Setting mg/dL (mmol/L) | True Alert Rate | False Alert Rate | Hyperglycemia Detection Rate | Hyperglycemia Missed Detection Rate |
| --- | --- | --- | --- | --- |
| 220 (12.2) | 91% | 9% | 95% | 5% |
| 240 (13.3) | 91% | 9% | 94% | 6% |
| 300 (16.7) | 82% | 18% | 86% | 14% |

## Hyperglycemia Alert Rate:

The Alert Rate shows how often the alert was right or wrong. The True Alert Rate is the % of time the device alarmed when the blood glucose level was at or above the alert setting within 15 minutes before or after the device alarmed. The False Alert Rate is the % of time the device alarmed when the blood glucose level was below the alert setting within 15 minutes before or after the device alarmed.

## Hyperglycemia Detection Rate:

The Detection Rate shows how often the device recognized and alerted that there was an episode of hyperglycemia or how often it missed such an event. The Hyperglycemia Detection Rate is the % of time the blood glucose level was at or above the alert setting and the device alarmed within 15 minutes before or after the blood glucose was at or above the alert settings. The Hyperglycemia Missed Detection Rate is the % of time the blood glucose was at or above the alert setting, but the device did not alarm within 15 minutes before or after the blood glucose was at or above the alert setting.

## Calibration Stability:

The System must be calibrated every 12 hours. To demonstrate performance of the System over a 12-hour calibration period, Sensors were evaluated to verify that performance remains consistent over the 12-hour calibration period. Systems were evaluated in 2-hour increments after calibration and performance was estimated at each 2-hour interval and stratified by glucose concentrations by calculating the percentage of System readings within 15 mg/dL (0.9 mmol/L) or 15%, 20 mg/dL (1.1 mmol/L) or 20%, 30 mg/dL (1.7 mmol/L) or 30%, 40 mg/dL (2.2 mmol/L) or 40% and greater than 40 mg/dL (2.2 mmol/L) or 40% of the YSI values in Table 11.

Table 11. Percentage of System Readings within YSI Laboratory Values with data stratified in 2-hour increments after calibration.

| Time from Calibration | Number of Paired System YSI | Percent within 15/15% | Percent within 20/20% | Percent within 30/30% | Percent within 40/40% | Percent greater Than 40/40% |
| --- | --- | --- | --- | --- | --- | --- |
| 0-2 hours | 1929 | 78% | 88% | 96% | 98% | 2% |
| 2-4 hours | 1516 | 69% | 81% | 91% | 96% | 4% |
| 4-6 hours | 1547 | 69% | 79% | 91% | 95% | 5% |

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| Time from Calibration | Number of Paired System-YSI | Percent within 15/15% | Percent within 20/20% | Percent within 30/30% | Percent within 40/40% | Percent greater Than 40/40% |
| --- | --- | --- | --- | --- | --- | --- |
| 6-8 hours | 1520 | 68% | 79% | 92% | 97% | 3% |
| 8-10 hours | 1555 | 71% | 82% | 92% | 96% | 4% |
| 10-12 hours | 1068 | 65% | 77% | 91% | 96% | 4% |
| 12-14 hours | 17 | 65% | 76% | 82% | 88% | 12% |

Note: CGM readings are within 40 to 400 mg/dL (2.2-22.2 mmol/L).

## Sensor Life and Sensor Stability:

**Sensor Life:** Sensors can be worn for up to 7 days (168 hours). To estimate how long a sensor will work over 7 days, 108 sensors were evaluated to determine how many days/hours of readings each sensor provided. Ninety-four percent (94%) of the sensors lasted until day 7 (145-168 hours). There were 6 (4%) sensors that ended early, four (4) of which lasted more than 3 days.

**Sensor Stability:** To assess the stability of sensor performance over the 7 day time period, 108 sensors were evaluated across the 7-day wear period. Performance was estimated by calculating the percentage of System readings within 15 mg/dL (0.9 mmol/L) or 15%, 20 mg/dL (1.1 mmol/L) or 20%, 30 mg/dL (1.7 mmol/L) or 30%, 40 mg/dL (2.2 mmol/L) or 40% and greater than 40 mg/dL (2.2 mmol/L) or 40% of the YSI values at the beginning (Day 1), middle (Day 4) and end (Day 7) of the System lifecycle. The average and median of the absolute percent differences are included in the table below (Table 12).

Table 12. System Sensor Stability (Accuracy over Time).

| Day of Wear | Number of Paired System-YSI | Mean Absolute Percent Differences (%) | Median Absolute Percent Differences (%) | Percent within 15/15% YSI | Percent within 20/20% YSI | Percent within 30/30% YSI | Percent within 40/40% YSI | Percent greater than 40/40% YSI |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Day 1 | 3023 | 16.7% | 13.7% | 59% | 71% | 86% | 94% | 6% |
| Day 4 | 3108 | 11.4% | 8.2% | 77% | 87% | 95% | 98% | 2% |
| Day 7 | 3021 | 11.9% | 8.9% | 76% | 87% | 95% | 98% | 2% |

Note: CGM readings are within 40 to 400 mg/dL (2.2-22.2 mmol/L).

## Accuracy of Rate of Glucose Change:

The percentage of concurring CGM readings and YSI values at different rates of glucose change (ROC) are described in table 13 below.

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Table 13. Concurrence of CGM and YSI at different rate of changes (ROC).

| CGM ROC mg/dL/min | YSI ROC (mg/dL/min)
Percent of matched pairs in each YSI glucose range for each Sensor glucose range | | | | | | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | (<-3) | (-3,-2) | (-2,-1) | (-1,1) | (1,2) | (2,3) | (>3) | Total |
| (<-3) | 5
17.2% | 7
24.1% | 12
41.1% | 5
17.2% | 0
0.0% | 0
0.0% | 0
0.0% | 29 |
| (-3,-2) | 5
7.7% | 15
23.1% | 24
36.9% | 21
32.3% | 0
0.0% | 0
0.0% | 0
0.0% | 65 |
| (-2,-1) | 5
1.4% | 31
8.9% | 124
35.4% | 190
54.3% | 0
0.0% | 0
0.0% | 0
0.0% | 350 |
| (-1,1) | 17
0.2% | 38
0.5% | 187
2.4% | 7292
91.8% | 317
4.0% | 70
0.9% | 21
0.3% | 7942 |
| (1,2) | 0
0.0% | 0
0.0% | 1
0.2% | 254
42.5% | 247
41.3% | 73
12.2% | 23
3.8% | 598 |
| (2,3) | 0
0.0% | 0
0.0% | 0
0.0% | 77
31.4% | 93
38.0% | 53
21.6% | 22
9.0% | 245 |
| (>3) | 0
0.0% | 0
0.0% | 0
0.0% | 10
10.3% | 38
39.2% | 31
32.0% | 18
18.6% | 97 |

## Precision of the System Reading:

A subgroup of 36 subjects wore two Systems (one blinded) during the study to assess the Sensor precision of two Systems worn on the same patient at the same time. Imprecision was evaluated using Paired Absolute Relative Difference (PARD) and Percent Coefficient of Variation (PCV). According to the sponsor PARD is the absolute value of the blinded Sensor minus the un-blinded. Sensor divided by the average of the two Sensor values. Percent coefficient of variation is the standard deviation of the two G4 Sensors divided by the average of the two Sensor values. The mean PARD of the System during the study was 9.3% with a coefficient of variation of 6.6% which demonstrates acceptable agreement.

## Number of Readings Provided:

The System is capable of providing a reading up to every 5 minutes (up to 288 readings per day). For a variety of reasons, the System may not display a glucose reading and readings are “skipped.” The number of actual Sensor values provided to subjects over the entire 7-day period and the corresponding percentage is summarized below in Table 14. Adjusted within each system wear-day, the System provided an average of 97% of all expected glucose readings (288) as seen in Table 15.

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Table 14. Number of Readings Provided by Each Sensor over 7-Days.

| % of Total Possible Readings Provided | Total Readings Provided (Min-Max) | % of Systems Providing that Number of Readings |
| --- | --- | --- |
| 0-25% | 167-491 | 1.9% |
| 26-50% | 719-914 | 3.7% |
| 51-75% | 1267-1267 | 0.9% |
| 76-100% | 1811-1992 | 93.5% |

Table 15. System Readings within Wear Days.

| | Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | Day 7 | All Days (N=108) |
| --- | --- | --- | --- | --- | --- | --- | --- | --- |
| Mean | 98% | 98% | 98% | 98% | 97% | 99% | 95% | 97% |
| Median | 100% | 100% | 100% | 100% | 100% | 100% | 100% | 100% |
| STD | 5% | 3% | 9% | 8% | 10% | 3% | 11% | 8% |

## Agreement and Accuracy Relative to SMBG:

During the study, agreement between the System and blood glucose values was also characterized using paired System and self-monitoring blood glucose (SMBG) meters results (see Tables 16 and 17 below). The System and SMBG values were compared by pairing the comparative SMBG value to a System glucose reading that occurred immediately after the SMBG was collected. These results characterize the performance patients expect during real-time use of the system in their daily diabetes management when comparing the system readings to their home blood glucose meter results. Both Tables (tables 16 and 17) are categorized within CGM glucose ranges (first column). CGM readings within the measuring range of the device (40-400 mg/dL glucose) are included in this analysis.

In Table 16, for the readings less than or equal to $80\mathrm{mg/dL}$ (4.4 mmol/L) glucose the absolute difference in mg/dL (mmol/L) between the two glucose results was calculated. For glucose values greater than $80\mathrm{mg/dL}$ (4.4 mmol/L) the absolute percent difference (%) from the SMBG values was calculated. The percentages of total readings within $15\mathrm{mg/dL}$ (0.8 mmol/L) or $15\%$, $20\mathrm{mg/dL}$ (1.1 mmol/L) or $20\%$, $30\mathrm{mg/dL}$ (1.7 mmol/L) or $30\%$, $40\mathrm{mg/dL}$ (2.2 mmol/L) or $40\%$ or greater than $40\mathrm{mg/dL}$ (2.2 mmol/L) or $40\%$ were then calculated.

Overall, the System read, on average, $0.3\%$ lower (Mean Percent Difference) than SMBG values and $13.9\%$ absolute different (Mean Absolute Difference) than the SMBG values. The Median Percent Difference showed that half of the time the System read $-1.2\%$ or less than the SMBG values and the Median Absolute Difference shows that half of the time the System read about $10.9\%$ or less different than SMBG values (Table 16).

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Table 16. System Agreement to SMBG within CGM Glucose Ranges.

| CGM Glucose Ranges mg/dL (mmol/L) | Number of Paired System SMBG | Percent within 15/15% SMBG | Percent within 20/20% SMBG | Percent within 30/30% SMBG | Percent within 40/40% SMBG | Percent greater than 40/40% SMBG |
| --- | --- | --- | --- | --- | --- | --- |
| Overall | 7508 | 69% | 81% | 94% | 98% | 2% |
| 40-60 (2.2-3.3) | 731 | 75% | 84% | 92% | 96% | 4% |
| 61-80 (3.4-4.4) | 968 | 78% | 86% | 95% | 99% | 1% |
| 81-180 (4.5-10.0) | 3141 | 65% | 78% | 93% | 98% | 2% |
| 181-300 (10.1-16.7) | 1960 | 68% | 81% | 94% | 97% | 3% |
| 301-350 (16.7-19.4) | 450 | 77% | 88% | 98% | 99% | 1% |
| 351-400 (19.4-22.2) | 258 | 75% | 85% | 95% | 98% | 2% |

*For CGM ≤ 80 mg/dL (4.4 mmol/L), the differences in mg/dL (mmol/L) are included instead of percent differences (%). Note: CGM readings are within 40 to 400 mg/dL (2.2-22.2 mmol/L).

For the analysis presented in Table 17, the Mean and Median Percent Difference and the Mean and Median Absolute Percent Difference were calculated to further illustrate the comparison between CGM readings and SMBG results. Overall, the System read, on average, 0.4% lower (Mean Percent Difference) than SMBG values and 14.0% absolute different (Mean Absolute Difference) than the SMBG values. The Median Percent Difference showed that half of the time the System read -1.4% or less than the SMBG values and the Median Absolute Difference shows that half of the time the System reads about 11.0% or less different than SMBG values (Table 17).

Table 17. System Difference to SMBG within CGM Glucose Ranges.

| CGM Glucose Ranges mg/dL (mmol/L) | Number of Paired System SMBG | Mean Percent Difference (%) | Median Percent Difference (%) | Mean Absolute Percent Difference (%) | Median Absolute Percent Difference (%) |
| --- | --- | --- | --- | --- | --- |
| Overall | 7508 | -0.4 | -1.4 | 14.0 | 11.0 |
| *40-60 (2.2-3.3) | 731 | -9.3 (-0.5) | -8.0 (-0.4) | 11.7 (0.7) | 8.0 (0.4) |
| *61-80 (3.4-4.4) | 968 | -1.0 (-0.1) | 1.0 (0.1) | 10.7 (0.6) | 8.0 (0.4) |

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| CGM Glucose Ranges mg/dL (mmol/L) | Number of Paired System-SMBG | Mean Percent Difference (%) | Median Percent Difference (%) | Mean Absolute Percent Difference (%) | Median Absolute Percent Difference (%) |
| --- | --- | --- | --- | --- | --- |
| 81-180 (4.5-10.0) | 3141 | 1.4 | 0.0 | 14.2 | 11.0 |
| 181-300 (10.1-16.7) | 1960 | -0.7 | -2.8 | 13.0 | 10.3 |
| 301-350 (16.7-19.4) | 450 | 0.7 | -2.6 | 10.5 | 8.6 |
| 351-400 (19.4-22.2) | 258 | 5.0 | 3.0 | 11.9 | 8.6 |

Note: CGM readings are within 40 to 400 mg/dL (2.2-22.2 mmol/L).

## 3. Subgroup Analyses

G4 system performance was evaluated within study population subgroups, such as in-clinic day 1, 4 and 7 participation group, diabetes type, age (18-20 years old transitional adolescent, 21 years old and above), body mass index (BMI), Baseline HbA1C (quartile groups) and type of diabetes medication (insulin, oral agent).

Although not powered for analysis of subpopulations, no significant differences in performance were noted based on age, BMI, ethnicity, %HbA1C, gender, or diabetes treatment.

Exercise: Forty-four (44) subjects participated in mild to moderate physical exercise activities during the in-clinic sessions. The System performance was evaluated prior to and following mild to moderate exercise. The system performance measures (MRD, MARD) were measured within each subject in reference to the laboratory standard (YSI). The mean relative difference was 1.4% prior to exercise vs. 7.5% following exercise and the MARD was 14.1% prior to and 20.2% following exercise. However, these results are not statistically significant (Kruskal-Wallis test p-value &gt;0.05). The blood samples were not arteiolized during this study since the participants were not wearing a heating pad during exercise. Therefore, it is not clear whether the changes that were seen during the study were due to blood sample differences or due to blood glucose levels changing rapidly due to the exercise.

## XI. PANEL MEETING RECOMMENDATION AND FDA'S POST-PANEL ACTION

In accordance with the provisions of section 515(c)(2) of the act as amended by the Safe Medical Devices Act of 1990, this PMA was not referred to the Clinical Chemistry and Clinical Toxicology Devices Panel, an FDA advisory committee, for review and

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recommendation because the information in the PMA substantially duplicates information previously reviewed by this panel.

# XII. CONCLUSIONS DRAWN FROM PRECLINICAL AND CLINICAL STUDIES

## A. Effectiveness Conclusions

The results of the pivotal clinical study performed in this submission establish a reasonable assurance of safety and effectiveness with the Dexcom G4 Platinum System for detecting trends and tracking patterns when used as intended, as an adjuvant to blood glucose testing in subjects with diabetes mellitus. The primary effectiveness measurements for this study were based on the performance evaluation of the Dexcom G4 Platinum System compared to the blood glucose values measured by YSI during in-clinic sessions that were obtained in the in-clinic sessions spanning the wear period of the sensor (days 1, 4, and 7).

The performance data presented above (Tables 5 to 17) support the effectiveness conclusions and established the accuracy across the claimed measuring range (40 to 400 mg/dL glucose), precision, and the claimed calibration frequency (calibrate every 12 hours), the 7 day wear period for the sensor, the alarms and alerts, and the number of readings displayed in the 7 day wear period.

The clinical study data demonstrate that the G4 PLATINUM CGM System was effective in the study population designed to be reflective of the intende…