Pilot Study 3 of Outpatient Control-to-Range: Safety and Efficacy With Day-and-Night In-Home Use

The study phases are as follows:

- Screening visit to see if you are eligible for the study and to determine how long you
will need to use the study CGM (visit 1)

- Up to 3 weeks using the study CGM (depends on your current CGM use), followed by an
office visit (visit 2)

- 2 weeks using the study insulin pump and study CGM together

- Full day visit in clinic or hotel for training using the system (visit 3)

- 1 week using the system without automated insulin delivery or suspension

- 2-day hotel or clinic visit for closed-loop training (visit 4),

- 16-19 days using the system in the evening and overnight only followed by an office
visit (visit 5)

- 16-19 days using the system for the full 24 hours

- Final study clinic visit (visit 6)

- Option 5 month extension phase of day-and-night closed-loop home use

Inclusion Criteria:

1. Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least
one year and using insulin for at least 1 year and an insulin pump for at least 6
months.

2. Age >=18 to <70 years.

3. HbA1c <10.0%; if HbA1c <6.0% then total daily insulin must be >=0.5 U/kg

4. For females, not currently known to be pregnant. If female and sexually active, must
agree to use a form of contraception to prevent pregnancy while a participant in the
study. A negative urine pregnancy test will be required for all premenopausal women
who are not surgically sterile. Subjects who become pregnant will be discontinued from
the study.

5. Demonstration of proper mental status and cognition for the study.

6. Currently using insulin-to-carbohydrate ratio to calculate meal bolus sizes

7. Hypoglycemia awareness as demonstrated by a Clarke Hypoglycemia Awareness score of 2
or lower

8. Access to internet and cell phone service at home, and a computer for downloading
device data.

9. Living with significant other or family member committed to participating in all
training activities, knowledgeable at all times of the participant's location, and
being present and available to provide assistance when system is being used at night.

10. Commitment to maintaining uninterrupted availability via cell phone and avoiding any
overnight travel for the duration of each two-week period using the closed-loop
system.

11. An understanding of and willingness to follow the protocol and sign the informed
consent.

Exclusion Criteria:

1. Admission for diabetic ketoacidosis in the 12 months prior to enrollment.

2. Severe hypoglycemia resulting in seizure or loss of consciousness in the 12 months
prior to enrollment.

3. History of a seizure disorder (except hypoglycemic seizure), unless written clearance
is received from a neurologist.

4. Coronary artery disease or heart failure, unless written clearance is received from a
cardiologist.

5. History of cardiac arrhythmia (except for benign premature atrial contractions and
benign premature ventricular contractions which are permitted)

6. Cystic fibrosis.

7. A known medical condition that in the judgment of the investigator might interfere
with the completion of the protocol such as the following examples:

- Inpatient psychiatric treatment in the past 6 months for either the subject or
the subject's primary care giver (i.e., parent or guardian)

- Presence of a known adrenal disorder

- Abnormal liver function test results (Transaminase >2 times the upper limit of
normal); testing required for subjects taking medications known to affect liver
function or with diseases known to affect liver function

- Abnormal renal function test results (calculated GFR <60); testing required for
subjects with diabetes duration of greater than 5 years post onset of puberty

- Active gastroparesis

- If on antihypertensive, thyroid, anti-depressant or lipid lowering medication,
lack of stability on the medication for the past 2 months prior to enrollment in
the study

- Uncontrolled thyroid disease (TSH undetectable or >10); testing required within
three months prior to admission for subjects with a goiter, positive antibodies,
or who are on thyroid hormone replacement, and within one year otherwise

- Abuse of alcohol or recreational drugs

- Infectious process not anticipated to resolve prior to study procedures (e.g.
meningitis, pneumonia, osteomyelitis)

7. A recent injury to body or limb, muscular disorder, use of any medication, any
carcinogenic disease, or other significant medical disorder if that injury, medication or
disease in the judgment of the investigator will affect the completion of the protocol 8.
Current use of the following drugs and supplements:

- Acetaminophen

- Any medication being taken to lower blood glucose, such as Pramlintide, Metformin,
GLP-1 Analogs such as Liraglutide, and nutraceuticals intended to lower blood glucose

- Beta blockers

- Oral or injectable glucocorticoids

- Any other medication that the investigator believes is a contraindication to the
subject's participation