Dose-Ranging, Pharmacokinetic (PK), Glucodynamic (GD), Safety and Tolerability Study of Subcutaneously (SC) Administered Humulin R and Humalog With or Without rHuPH20

Subjects will be enrolled in one of four sequential study stages. In each stage, a euglycemic
clamp procedure will be used to control plasma glucose levels. Blood samples will be
collected over an 8-hour time period after insulin administration (either Humulin R or
Humalog) to analyze insulin and glucose levels using fully validated methods. Glucose
infusion rates (GIR) will be recorded throughout the study period. The study is single-blind,
with study subjects blinded as to the contents of each injection.

Determine the pharmacokinetics (PK) and optimum ratio of rHuPH20:insulin when a range of
rHuPH20 dose ratios are administered subcutaneously (SC) with fixed doses of Humulin R, by
determining Tmax, Cmax, AUCs, and relative bioavailability based on serum insulin
concentrations collected at specified time points (Stage 1).

Determine if different concentrations of Humulin R impact the PK and minimal rHuPH20 dose
necessary to achieve full insulin PK effect over a representative range of typical prandial
SC Humulin R doses using the rHuPH20:insulin ratio identified in Stage 1 (Stage 2).

Determine the PK and optimum ratio of rHuPH20:insulin when a range of rHuPH20 dose ratios are
administered SC with fixed doses of Humalog, by determining Tmax, Cmax, AUCs, and relative
bioavailability based on serum insulin concentrations collected at specified time points
(Stage 3).

Determine if different concentrations of Humalog impact the PK and minimal rHuPH20 dose
necessary to achieve full insulin PK effect over a representative range of typical prandial
SC Humalog doses using the rHuPH20:insulin ratio identified in Stage 3 (Stage 4).

Evaluate the safety and local tolerability of the SC injection at various rHuPH20, Humulin R,
and Humalog doses (Stages 1 - 4).

Assess the glucodynamics (GD) of the SC injection of various rHuPH20, Humulin R, and Humalog
doses (Stages 1 - 4).

Inclusion Criteria:

- Healthy subjects between the ages of 18 and 55 years, inclusive. (Healthy is defined
as no clinically relevant abnormalities identified by a detailed medical history, full
physical examination (PE), including blood pressure (BP) and heart rate (HR), 12-lead
electrocardiogram (ECG) and clinical laboratory tests specified in these eligibility
criteria).

- BMI between 18-28 kg/m2, inclusive.

- Total body weight >70 kg (154 lb) for men and 46 kg (101 lb) for women.

- Subject willing and able to comply with scheduled visits, treatment plan, laboratory
tests, and other study procedures including adequate venous access.

- Vital signs (BP, HR, temperature, respiratory rate) within normal range or, if out of
range, assessed by the Principal Investigator (PI) as not clinically significant (NCS)
and mutually agreed by both PI and the Sponsor's medical monitor that the subject need
not be excluded from the study for this abnormal value.

- Within 14 days before the first injection: metabolic panel (e.g., sodium, potassium,
chloride, bicarbonate, BUN (blood urea nitrogen), creatinine, glucose, calcium, AST
(aspartate transaminase [SGOT]), ALT (alanine transaminase [SGPT]), alkaline
phosphatase, total bilirubin, albumin, cholesterol, lipids, amylase and total protein)
and complete blood count (CBC) within the laboratory normal reference range or, if out
of range, assessed by the PI as NCS and mutually agreed by both PI and the Sponsor's
medical monitor that the subject need not be excluded from the study for this
laboratory value.

- Fasting plasma glucose level within the range of 60 to 100 mg/dL, inclusive, within 30
minutes of the first euglycemic clamp.

- A negative serum pregnancy test (if female of childbearing potential) within 14 days
of study drug injection.

- Female subjects of childbearing potential must agree to be practicing effective birth
control or abstinence currently and agree to continue to do so for the duration of
their time on study.

- Decision-making capacity and willingness and ability to comply with the requirements
for full completion of the study.

- Signed, written IRB-approved informed consent.

Exclusion Criteria:

- Evidence or history of clinically significant hematological, renal, endocrine,
pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, oncologic, or
neurologic (to include history of seizures) disease; hypoglycemic episodes;
intercurrent illness (such as influenza); or allergic disease (including drug
allergies, but excluding untreated, asymptomatic, seasonal allergies at time of
dosing). Clinical significance to be determined by the PI.

- Known history of diabetes mellitus or gestational diabetes.

- Known allergy to hyaluronidase or any other ingredient in the study drug.

- Positive HIV 1 and HIV 2 (human immunodeficiency virus) antibody test, hepatitis B
(anti-HBsAg) or hepatitis C (anti-HCV) antibody test.

- Any history or evidence of alcohol or drug abuse.

- History or evidence of use of any tobacco- or nicotine-containing product within 6
months of screening, screening quantitative urine nicotine concentration >50 ng/mL, or
screening serum cotinine concentration of > 20 ng/mL.

- Use of drugs that may interfere with the interpretation of trial results or are known
to cause clinically relevant interference with insulin action or glucose utilization.

- Donation of blood in excess of 500 mL within 56 days before dosing.

- Failure to limit alcohol consumption and refrain from exercise within 48 hours before
each injection.

- Participation in a study of any investigational drug or device 30 days before
enrollment in this study.

- The subject is unfit for the study in the opinion of the investigator.

- Women who are pregnant or breast-feeding.