Lisofylline as Continuous Subcutaneous and Intravenous Administration in Subjects With Type 1 Diabetes Mellitus

This is an open-label, randomized, crossover study in subjects with type 1 diabetes. There
are two treatment periods separated by approximately one week. One treatment will consist
of a 10 hour subcutaneous infusion of lisofylline, and the other treatment will consist of a
10 hour intravenous infusion of lisofylline.

Eligible subjects will be admitted to the Infusion Center the morning of dosing (Day 1, Day
7) during each treatment period, receive their assigned dose of study drug on Day 1 and Day
7, and will remain confined to the Infusion Center until approximately 3 hours following the
start of study drug administration for the remaining blood draws. The subjects will then be
escorted to the Sleep Center of Eastern Virginia Medical School for an overnight stay during
which time their heart rate and oxygen saturation will be monitored by pulse oximetry. The
next morning the subjects will return to the Infusion Center for a final blood draw and
physical examination. The Infusion Center and the Sleep Disorders Center are both within
Sentara Norfolk General Hospital.

All subjects will be assigned to a treatment sequence according to a randomization schedule.

Inclusion Criteria:

- Male or female adults between the ages of 18 and 45 years of age

- Ability to understand and provide written informed consent

- Ability to complete the study in compliance with the protocol

- If female, subjects must be non-pregnant and non-lactating, and willing to use
appropriate and adequate contraception during the study

- If male, subjects must be willing to use effective birth control during the study

- Weight at least 50 kgs (110 lbs)

- Body mass index between 18.5 and 30 kg/m2

- QTc < 450 msec at screening

- Clinical diagnosis of type 1 diabetes at least 2 years prior to screening

- Treatment with insulin for at least 1 year and on a stable dose for at least 3 months
prior to screening (dose must be < 0.8 units/kg/day)

- Subjects must self-monitor blood glucose levels at least daily

- HbA1c 6-9%

- Serum c-peptide level < 0.6 ng/mL

- Serum creatinine < 1.5 mg/dL for males and < 1.4 mg/dL for females

- Negative hepatitis B, hepatitis C and HIV testing at screening or within 3 months of
screening

- Subjects must be free from clinically significant abnormal findings at the time of
screening (to include abnormalities on examination, medical history,
electrocardiogram, clinical laboratory testing); to be determined by principal
investigator

Exclusion Criteria:

- Subjects with significant stomach, liver, kidney or heart disease, including high
blood pressure, stroke or other blood vessel disease. Significant eye problems due to
diabetes, diabetic nerve disease, or non-healed diabetic foot ulcers

- Personal or family history of long QTc syndrome

- History of clinically significant changes in orthostatic blood pressure

- Clinically significant changes in orthostatic blood pressure at screening

- History of peptic ulcer disease and/or gastrointestinal bleeding/perforation

- History or presence of proliferative retinopathy, severe non-proliferative
retinopathy, macular edema or presence of untreated diabetic eye disease

- History of severe peripheral or autonomic neuropathy in the opinion of the study
physician

- History of hypoglycemia unawareness, and/or episodes of severe hypoglycemia within 60
days of screening

- Diagnosis of type 2 diabetes, based upon subject report

- Use of oral antihyperglycemic medications, pentoxyifylline, and/or theophylline

- Use of any drug therapy that directly affects gastrointestinal motility

- History of any significant drug allergy

- History of difficulty with phlebotomy

- Use of any recreational drugs within the past year or a previous history of drug or
alcohol abuse

- Positive results from a screen for alcohol or substances of abuse at screening or
upon admission to the study site

- Current smoker or user of any tobacco products

- Use of prescription medications is acceptable at the Principal Investigator's
discretion if they have been part of a stable drug regimen documented for the last 60
days. Drug therapy should be held the morning of Day 1 and Day 7 at the Principal
Investigator's discretion

- use of any over-the-counter drugs or herbal preparations within 72 hours prior to
receiving study drug

- Consumption of any caffeine-containing foods or beverages within 24 hours prior to
receiving study drug

- Consumption of alcohol within 24 hours prior to admission to the study site

- Consumption of any grapefruit or grapefruit-containing juices within 72 hours prior
to receiving study drug

- Use of an investigational drug or product, or participation in a drug research study
within 30 days prior to receiving drug

- Prior exposure to lisofylline

- Donation of blood (1 pint or more) within 30 days or plasma within 7 days of
receiving study drug

- Any condition which in the opinion of the study investigator would interfere with the
participant's ability to provide informed consent, comply with study instructions,
possibly confound interpretation of study results, or endanger the participant if he
or she took part in the trial