In Clinic Evaluation of the PLGM Feature
In Clinic Evaluation of the PLGM Feature
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.
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:

 1. PLGM is activated

 2. 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).

 3. Neither condition for #1 or #2 has been met in 12 hours

 Observation with YSI ends when:

 1. 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.

 2. 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

 3. Twelve hours have passed since the start of hypoglycemic induction without PLGM
 activation

 4. 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.

 1. The investigational centers will be encouraged to include subjects of different
 ethnicities including Hispanic, Native American, and African-American

 2. 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.
Inclusion Criteria:

 1. Subject is 14-75 years of age at time of screening

 2. 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

 3. On pump therapy at the time of screening with insulin sensitivity and insulin
 carbohydrate ratio

 4. Adequate venous access as assessed by investigator or appropriate staff

 Exclusion Criteria:

 Exclusion Criteria that are Based on Demands of In-Clinic Study Procedures

 1. Subject is unable to tolerate tape adhesive in the area of sensor placement

 2. Subject has any unresolved adverse skin condition in the area of sensor or device
 placement (e.g., psoriasis, rash, Staphylococcus infection)

 3. 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

 4. Subject has a positive urine or serum pregnancy screening test

 5. Subject is female, sexually active without use of contraception and plans to become
 pregnant during the course of the study

 6. Subject has had a hypoglycemic induced seizure within the past 6 months prior to
 screening visit

 7. Subject has had hypoglycemia resulting in loss of consciousness within the past 6
 months prior to screening visit

 8. Subject has had an episode of diabetic ketoacidosis (DKA) within the past 6 months
 prior to screening visit

 9. Subject has a history of a seizure disorder

 10. Subject has central nervous system or cardiac disorder resulting in syncope

 11. 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

 12. Subjects with hematocrit (Hct) lower than the normal reference range for age per local
 lab testing

 13. Subjects with a history or findings on screening electrocardiogram (EKG) of any
 cardiac arrhythmia, including atrial arrhythmias

 14. Subjects with a history of adrenal insufficiency

 15. Subjects with history of migraines that have occurred at least 2 times in the last 3
 months prior to enrollment