Effect of a Fixed Pramlintide: Insulin Dose Ratio on Postprandial Glucose in Type 1 Diabetes Mellitus

Potentially eligible subjects with Type 1 diabetes mellitus who are treated with with a
basal-bolus insulin regimen through multiple daily injections or insulin pump at a total
daily insulin dose ≤60 U, will be eligible. Visit 1 is approximately 3-6 weeks prior to
randomization. Given some variability in HbA1c and C-peptide assays, re-testing for HbA1c and
C-peptide can be performed within 18 days from the initial visit. Visit 2 is approximately
2-5 weeks prior to randomization. Subjects are on lispro insulin throughout study except
during Visit 4 and Visit 5, the domicile 24 hr treatment period, when they are switched to
regular insulin U-100.

Screen failed patients may be re-screened for inclusion in the study, as long as re-screening
takes place at least 3 months after the original screening visit. If a subject is
re-screened, he/she must continue to meet all inclusion/exclusion criteria. All study
procedures of initial Visit 1 must be repeated at the re-screening visit.

Inclusion Criteria:

- Provision of informed consent prior to any study-specific procedures

- Female and/or male aged between 18 and 70 years

- Must have a prior diagnosis of T1DM

- Body mass index (BMI) <30 kg/m2

- Subjects are not on current treatment with pramlintide (Symlin) and have not received
pramlintide during the 6-month period prior to enrollment

- Subjects should be willing to consume all of the components of the standardized meals
administered during the study

- Negative serum pregnancy test for female subjects of childbearing potential

- Female subjects of childbearing potential must be 1 year postmenopausal, surgically
sterile, or using an acceptable method of contraception for the duration of the study

- Male subjects must be surgically sterile or using an acceptable method of
contraception for the duration of the study

Exclusion Criteria:

- Recurrent severe hypoglycemia requiring assistance within 6 months before screening

- A history of hypoglycemia unawareness

- A confirmed diagnosis of gastroparesis

- Has been treated, is currently being treated, or is expected to require or undergo
treatment with the following medications:

- Any oral antihyperglycemic agent or any other injectable antihyperglycemic agent that
is not insulin

- Drugs that directly affect GI motility (eg, anticholinergic agents such as atropine)

- Drugs that slow the intestinal absorption of nutrients (eg, α-glucosidase inhibitors

- A history of gastric surgery (such as gastric banding, Roux- and Y bypass)

- Is expected to require or undergo treatment with acetaminophen after enrollment and at
any point during the study

- Has experienced diabetic ketoacidosis within the last 24 weeks

- History of hospitalization within the last 6 months for glycemic control (for both
hyperglycemia or hypoglycemia)

- Subject has any significant disease or disorder, which, in the opinion of the
investigator, may either put the subject at risk because of participation in the
study, or may influence the results of the study, or the subject's ability to
participate in the study

- Any clinically relevant abnormal findings, which, in the opinion of the investigator,
may put the subject at risk because of his/her participation in the study.

- Pregnancy confirmed by a positive pregnancy test, or otherwise verified.

- Breast feeding

- Positive hepatitis C virus antibody (HCV Ab), hepatitis B virus surface antigen
(HBsAg), hepatitis B virus core antibody (anti-Hbc), or human immunodeficiency virus
1/2 antibody (HIV-1/2 Ab) at Screening

- History of, or current alcohol or drug abuse

- Has donated blood within 2 months of Visit 1 (Screening) or is planning to donate
blood during the study

- Has had a major surgery or a blood transfusion within 2 months before Visit 1
(screening)

- Participation in any clinical study with an investigational drug or new formulation of
a marketed drug during the last 1 month prior to Visit 1