Pharmacokinetic and Glucodynamic Crossover Study of SC Administered Insulin Lispro +rHuPH20 and Regular Human Insulin +rHuPH20 Compared to Insulin Lispro Alone

Inclusion Criteria:

• Healthy subjects between the ages of 18 and 55 years, inclusive. (Healthy is defined as no clinically relevant abnormalities)
• BMI between 18-27 kg/m2, inclusive.
• Total body weight >65 kg (143 lb) for men and >46 kg (101 lb) for women.
• Decision making capacity and willingness to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures including adequate venous access.
• Vital signs (BP, Pulse Rate, Body Temperature) within normal range or, if out of range, assessed by the Principal Investigator (PI) as not clinically significant (NCS).
• Fasting blood glucose level < 100 mg/dL at screening.
• A negative serum pregnancy test (if female of childbearing potential).
• 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.
• 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 severe drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing). Clinical significance to be determined by the PI.
• As judged by the Investigator, clinically significant findings in routine laboratory data. (Anemia with hematocrit less than 33% at screening is specifically exclusionary.)
• Known history of diabetes mellitus (type 1 or type 2) or gestational diabetes.
• Known allergy to hyaluronidase or any other ingredient in the study drug.
• Positive HIV 1 (human immunodeficiency virus) antibody test, hepatitis B (anti-HBsAg) or hepatitis C (anti-HCV) antibody test.
• 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 and a screening qualitative urine nicotine test.
• 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.
• 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.