Outpatient Study to Evaluate Safety and Effectiveness of the Low Glucose Suspend Feature

ASPIRE (Automation to Simulate Pancreatic Insulin Response): Pivotal In Home Study to Determine Safety and Efficacy of the LGS Feature in Sensor-augmented Pumps

Introduction:

The purpose of the pivotal In Home study is to collect clinical data on the safety and efficacy of the Paradigm LGS System in the actual use environment and by the intended use population. ASPIRE is a multi-center, in home, randomized parallel adaptive study design with type 1 diabetes. The study will compare A1C and CGM based nocturnal hypoglycemic events in a treatment arm to a control arm. Arms are defined as:

• Treatment Arm (LGS ON) using Paradigm® VEO™ Pump
• Control Arm (NO LGS FEATURE ) using Paradigm® Revel™2.0 Pump

The study's objectives are two-fold:

1. The first study objective is to demonstrate that home use of Low Glucose Suspend (LGS) is safe and is not associated with glycemic deterioration, as measured by change in A1C from baseline to end of study participation.
2. The second study objective is to demonstrate that home use of Low Glucose Suspend (LGS) is associated with reduction in nocturnal hypoglycemia when patients fail to respond.

Primary Safety Endpoint:

The change in A1C from randomization to the end of the treatment period will be used to demonstrate that the automatic insulin delivery suspension (LGS ON) does not result in an unacceptable worsening of glycemic control.

Inclusion Criteria:

• Subjects who are 16-21 years are determined by the investigator to have the appropriate, requisite support (family, caregiver or social network) to successfully participate in this study
• Subjects who are determined by the investigator to be psychologically sound in order to successfully participate in this study.
• Subject was < 40 years at disease onset
• Subject has been diagnosed with type 1 diabetes ≥ 2 years
• Subject is willing to perform ≥ 4 finger stick blood glucose measurements daily
• Subject is willing to perform required sensor calibrations
• Subject is willing to wear the system continuously throughout the study
• Subject is willing to keep a log to record at minimum:
• Sick days
• Days with exercise and days with symptoms of low glucose
• Subject has an A1C value 5.8% to 10.0% (as processed by Central Lab) at time of screening visit
• Subject must be on pump therapy use for >6 months prior to Screening
• Subject has been followed by a well trained diabetes health care provider(s) for 6 months prior to screening
• Subject is willing to upload data weekly from the study pump, must have Internet access and a computer system that meets the requirements for uploading the study pump
• If subject has celiac disease, it has been adequately treated as determined by the investigator
• Subject is willing to take one of the following insulins and can financially afford to use either of the 2 insulin preparations throughout the course of the study (i.e. co-payments for insulin with insurance or able to pay full amount)
• Humalog® (insulin lispro injection)
• NovoLog® (insulin aspart)

Exclusion Criteria:

• Subject has a history of 2 or more episodes of severe hypoglycemia, which resulted in any the following during the 6 months prior to screening:
• Medical assistance (i.e. Paramedics, Emergency room or Hospitalization)
• Coma
• Seizures
• 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 placement (e.g., psoriasis, rash, Staphylococcus infection)
• Women of child-bearing potential who have a positive pregnancy test at screening or plan to become pregnant during the course of the study
• Subject has had any of the following new diagnoses within 1 year of screening: myocardial infarction, unstable angina, coronary artery bypass surgery, coronary artery stenting, transient ischemic attack, cerebrovascular accident, angina, congestive heart failure, ventricular rhythm disturbances or thromboembolic disease
• Subject is being treated for hyperthyroidism at time of screening
• Subject has an abnormality (out of upper reference range, as processed by Central Lab) in creatinine at time of screening visit
• Subject has an abnormality (out of reference range, as processed by Central Lab) in thyroid-stimulating hormone (TSH) at time of screening visit
• Subject has taken any oral, injectable, or IV steroids within 8 weeks from time of screening visit, or plans to take any oral, injectable, or IV steroids during the course of the study
• Subject is actively participating in an investigational study (drug or device) wherein he/she has received treatment from an investigational study drug or investigational study device in the last 2 weeks
• Subject has been hospitalized or has visited the emergency room in the 6 months prior to screening resulting in a primary diagnosis of uncontrolled diabetes
• Subject is currently abusing illicit drugs
• Subject is currently abusing prescription drugs
• Subject is currently abusing alcohol
• Subject is using pramlintide (Symlin) at time of screening
• Subject has a history of visual impairment which would not allow subject to participate in the study and perform all study procedures safely, as determined by the investigator
• Subject has elective surgery planned that requires general anesthesia during the course of the study
• Subject is a shift worker with working hours between 10pm and 8am.
• Subject has a sickle cell disease, hemoglobinopathy; or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening
• Subject plans to receive red blood cell transfusion or erythropoietin over the course of study participation
• Subject diagnosed with current eating disorder such as anorexia or bulimia
• Subject plans to use significant quantity of herbal preparations (use of over the counter herbal preparation for 30 consecutive days or longer period during the study) or significant quantity of vitamin supplements (four times the recommended daily allowance used for 30 consecutive days or longer period during the study) during the course of their participation in the study
• Subject has been diagnosed with chronic kidney disease that results in chronic anemia
• Subject is on dialysis