Safety/Efficacy Study of Subcutaneously Injected Prandial Insulins Compared to Insulin Lispro Alone in Patients With Type 2 Diabetes Mellitus

A Phase II, Randomized, Double Blind, 2-Way Crossover Safety and Efficacy Study of Subcutaneously Injected Prandial Insulins: Lispro-PH20 or Aspart-PH20 Compared to Insulin Lispro (Humalog®) in Patients With Type 2 Diabetes

The purpose of the study was to compare Humalog (insulin lispro)-recombinant human hyaluronidase PH20 (rHuPH20) or Novolog (insulin aspart)-rHuPH20 to insulin lispro for the treatment of Type 2 diabetes mellitus (T2DM) in basal-bolus therapy.

Criteria for randomization into the study included 1) fasting blood glucose and pre-dinner glucose values in the range of 70 to 140 milligrams per deciliter (mg/dL) approximately 60% of the time for 7 days prior to randomization; 2) 90 minute or 2-hour postprandial blood glucose <220 mg/dL approximately 70% of the time for 7 days prior to randomization; and 3) successfully completing 3 days of 10-point glucose monitoring and have at least 4 self-monitored blood glucose values on all non-10-point monitoring days. Participants that did not meet 1 or more of these criteria during a 4- to 6-week Titration Period were not randomized.

Inclusion Criteria:

• Males or females ≥18 years
• Type 2 diabetes mellitus (T2DM) treated with insulin ≥12 months and prandial insulin (at least 2 meals per day) for ≥2 months
• Body mass index (BMI) of 23.0 to 45.0 kilograms per meter squared (kg/m^2)
• Glycosylated hemoglobin (HbA1C) level 7.0 to 8.5%, inclusive
• Fasting C-peptide <0.6 nanograms per milliliter (ng/mL)
• Willingness to use insulin glargine twice a day as basal insulin for the duration of the study
• Willingness to avoid use of an insulin infusion pump or unblinded continuous glucose monitoring (CGM) during the study

Exclusion Criteria:

• Known or suspected allergy to any component of any of the study drugs
• Exclusive use of pre-mixed insulins
• Use of pramlintide, exenatide, and/or liraglutide within 30 days of screening
• Use of sulfonylureas within two months of screening
• Use of drugs (such as corticosteroids or antimetabolites) that could interfere with the interpretation of study results or are known to cause clinically relevant interference with insulin action, glucose utilization, or recovery from hypoglycemia, during the study or within 30 days of screening
• Recurrent severe hypoglycemia (more than 2 episodes over the last 6 months) or hypoglycemic unawareness, as judged by the investigator