Liquid Meal Study With Insulin Lispro With/Without rHuPH20 and Regular Human Insulin With rHuPH20 to Compare Pharmacokinetics, Postprandial Glycemic Response, and Optimal Insulin Dose in Patients With T2DM

Inclusion Criteria:

• Male or female of age 18 to 70 years, inclusive.
• Patients with Type 2 diabetes mellitus per WHO criteria treated with basal and/or bolus insulin for ≥ 12 months.
• BMI between 18-45 kg/m2, inclusive.
• HbA1c (glycosylated hemoglobin A1c) ≤ 10%.
• Current treatment with insulin ≥ 60 Units/Day.
• A patient taking oral hypoglycemic agents must be on a stable dose for >8 weeks, with the exception of thiazolidinediones (TZD), which should be >12 weeks.
• Total body weight >65 kg (143 lb) for men and >46 kg (101 lb) for women.
• Vital signs (BP, Pulse Rate, and Body Temperature) within normal range or, if out of range, assessed by the Investigator as not clinically significant (NCS).
• Patients should be in good general health based on medical history and physical examination, without medical conditions that might prevent the completion of study drug injections and assessments in this protocol.
• Decision making capacity and willingness to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures including adequate venous access.
• Signed, written IRB-approved informed consent.

Exclusion Criteria:

• Known or suspected allergy to any components of any of the study drugs in this study.
• Previous enrollment in this study.
• A patient who has proliferative retinopathy or proliferative maculopathy, and/or severe neuropathy, in particular autonomic neuropathy as judged by the Investigator.
• As judged by the Investigator, clinically significant active disease of the gastrointestinal, cardiovascular (including a history of arrhythmia or conduction delays on ECG, and NYHA Class III/IV heart disease), hepatic, neurological, renal, genitourinary or hematological systems.
• As judged by the Investigator, uncontrolled hypertension (diastolic blood pressure ≥ 100 mmHg and/or systolic blood pressure ≥ 160 mmHg after 5 minutes in the supine position).
• As judged by the Investigator, clinically significant findings in routine laboratory data. (Anemia with hematocrit less than 33% at screening is specifically exclusionary).
• Positive HIV (human immunodeficiency virus) antibody test, hepatitis B (anti-HBsAg) or hepatitis C (anti-HCV) antibody test.
• Current addiction to alcohol or substances of abuse as determined by the Investigator.
• Known use of drugs (other than oral hypoglycemic agents) that may interfere with the interpretation of study results or are known to cause clinically relevant interference with insulin action, glucose utilization, or recovery from hypoglycemia.
• Recurrent major hypoglycemia or hypoglycemic unawareness, as judged by the Investigator.
• Mental incapacity, unwillingness, or language barriers precluding adequate understanding or cooperation in this study.
• Symptomatic gastroparesis.
• Donation of blood in excess of 500 mL within 56 days before dosing.
• Use of any investigational drug or device 30 days before enrollment in this study.
• Pregnancy, breast-feeding, the intention of becoming pregnant, or not using adequate contraceptive measures (adequate contraceptive measures consist of sterilization, intra-uterine device [IUD], oral or injectable contraceptives, barrier methods, or remaining abstinent).
• Any condition (intrinsic or extrinsic) that in the judgment of the Investigator will interfere with study participation or evaluation of data.