In Clinic Evaluation of the PLGM Feature

Study Overview
=================
Brief Summary
-----------------
This study is a multi-center, single arm and in-clinic study to evaluate the safety of the PLGM System and its algorithm with the Enlite 3 Sensor.

Detailed Description
-----------------
A total of up to 95 subjects with type 1 diabetes (age 14-75 years old) will be enrolled at up to 8 investigational centers in order to reach a minimum of 60 subjects who will complete the study (N=minimum 40 adult subjects, 22-75 years old) and N=minimum 15 pediatric subjects (14-21 years old). Subjects will be evaluated in an in-clinic setting with induction of hypoglycemia by increasing their basal rate using a standardized titration tool referred to in protocol as rate of change basal increase algorithm (Buckingham, Diabetes Care 5, 2010). Total duration of frequent sample testing (FST) using Yellow Springs Instrument (YSI) may be up to 19 hours. Subjects will undergo in-clinic testing on Sensor Day 1. All subjects will undergo hypoglycemic induction at Visit 2 with target set to 65 mg/dL using the rate of change basal increase algorithm. Low Limit setting when PLGM ON is 65 mg/dL. The In-Clinic part of the study consists of hypoglycemic induction and an observation period. Hypoglycemic induction ends when one of the following 3 criteria is met, whichever comes first: PLGM is activated YSI glucose is less than or equal to 65 mg/dL, followed by the next YSI sample less than or equal to 65 mg/dL (2 contiguous YSI samples). Neither condition for #1 or #2 has been met in 12 hours Observation with YSI ends when: If PLGM is activated, observation with YSI frequent sample testing will include the Suspend period (30 minutes minimum to 2 hours maximum) and insulin resumption period (approximately 4 hours from the time insulin delivery resumes). This may include insulin re-suspension during this period. Maximum observation with YSI frequent sample testing should be no longer than 19 hours. YSI glucose less than or equal to 65 mg/dL is followed by the next YSI sample less than or equal to 65 mg/dL (2 contiguous YSI samples). The subject will be rescued and YSI observation will end Twelve hours have passed since the start of hypoglycemic induction without PLGM activation See In-Clinic Stopping rules Enrollment for this study will proceed in phases. Phase 1 only allows enrollment of adult subjects (22-75 years). Subjects will wear pump system, as shown below: One Study Pump One GST-3C Transmitter One Enlite 3 Sensor Progression to Phase 2 may occur after 10 adult subjects have completed Phase 1 and a Data Safety Monitoring Board (DSMB) has approved that it is safe to continue on to Phase 2. Phase 2 enrollment involves a minimum of 15 pediatric subjects (14-21). Subjects will wear the same pump system as shown for Phase 1. A total of up to 95 subjects will be enrolled at up to 10 investigational centers in order to reach a minimum of 60 subjects (N=minimum 40 adult subjects and N=minimum 15 pediatric subjects) who will complete the study. Considering around 15% screen failure rate and approximately 15% drop-out rate, a total of up to 95 subjects will be enrolled in order to have 60 subjects complete the study. The investigational centers will be encouraged to include subjects of different ethnicities including Hispanic, Native American, and African-American Subjects will be grouped into cohorts by Age The study is anticipated to last no longer than 12 months from investigational center initiation to completion of all data entry and monitoring procedures including final report. Subjects can expect to participate for approximately 2-3 weeks.

Official Title
-----------------
In-Clinic Evaluation of the Predictive Low Glucose Management (PLGM) System in Adult and Pediatric Insulin Requiring Patients With Diabetes Using the Enlite 3 Sensor

Conditions
-----------------
Type 1 Diabetes

Intervention / Treatment
-----------------
* Device: Predictive Low Glucose Management Feature in Insulin pump


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject is 14-75 years of age at time of screening Subject has a clinical diagnosis of type 1 diabetes, as determined via medical record or source documentation by an individual qualified to make a medical diagnosis Inclusion Criteria that are Based on Demands of In-Clinic Study Procedures On pump therapy at the time of screening with insulin sensitivity and insulin carbohydrate ratio Adequate venous access as assessed by investigator or appropriate staff Exclusion Criteria: Exclusion Criteria that are Based on Demands of In-Clinic Study Procedures Subject is unable to tolerate tape adhesive in the area of sensor placement Subject has any unresolved adverse skin condition in the area of sensor or device placement (e.g., psoriasis, rash, Staphylococcus infection) Subject is actively participating in an investigational study (drug or device) wherein they have received treatment from an investigational study (drug or device) in the last 2 weeks Subject has a positive urine or serum pregnancy screening test Subject is female, sexually active without use of contraception and plans to become pregnant during the course of the study Subject has had a hypoglycemic induced seizure within the past 6 months prior to screening visit Subject has had hypoglycemia resulting in loss of consciousness within the past 6 months prior to screening visit Subject has had an episode of diabetic ketoacidosis (DKA) within the past 6 months prior to screening visit Subject has a history of a seizure disorder Subject has central nervous system or cardiac disorder resulting in syncope Subject has a history of myocardial infarction, unstable angina, coronary artery bypass surgery, coronary artery stenting, transient ischemic attack (TIA), cerebrovascular accident (CVA), angina, congestive heart failure, ventricular rhythm disturbances or thromboembolic disease Subjects with hematocrit (Hct) lower than the normal reference range for age per local lab testing Subjects with a history or findings on screening electrocardiogram (EKG) of any cardiac arrhythmia, including atrial arrhythmias Subjects with a history of adrenal insufficiency Subjects with history of migraines that have occurred at least 2 times in the last 3 months prior to enrollment

Ages Eligible for Study
-----------------
Minimum Age: 14 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Predictive Low Glucose Management (PLGM)<br>To evaluate the safety of the Predictive Low Glucose Management feature in insulin pump algorithm with the Enlite 3 Sensor | Device: Predictive Low Glucose Management Feature in Insulin pump<br>* All subjects will undergo hypoglycemic induction at Visit 2 with target set to 65 mg/dL using the rate of change basal increase algorithm. Low Limit setting when PLGM ON is 65 mg/dL.<br>* Other names: Medtronic MiniMed 640G Insulin Pump, MMT-1512;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serious Adverse Events (SAE) | Evaluation of incidence of SAE during in-clinic procedures | From start of in clinic procedures until the end of the study, which may occur up to 48 hours after the start of in-clinic procedures | 
| Unanticipated Device Effect (UADE) | Evaluation of incidence of UADE during in-clinic procedures | From start of in clinic procedures until the end of the study, which may occur up to 48 hours after the start of in-clinic procedures | 
| Severe Hypoglycemia | Evaluation of incidence of severe hypoglycemia during in-clinic procedures | From start of in clinic procedures until the end of the study, which may occur up to 48 hours after the start of in-clinic procedures | 
| Diabetic Ketoacidosis | Evaluation of DKA during in-clinic procedures | From start of in clinic procedures until the end of the study, which may occur up to 48 hours after the start of in-clinic procedures | 
| Rescue Events During In-clinic Procedues |  | From start of in clinic procedures until the end of the study, which may occur up to 48 hours after the start of in-clinic procedures |