Safety/Efficacy Study of Subcutaneously Injected Prandial Insulins Compared to Insulin Lispro Alone in Participants With Type 1 Diabetes Mellitus

Halozyme

Status and phase: Completed; Phase 2

Conditions: Diabetes Mellitus, Type 1

Treatments: Drug: Insulin lispro; Drug: Insulin aspart; Drug: Insulin glargine; Drug: Insulin glulisine; Drug: recombinant human hyaluronidase PH20

Study type: Interventional

Funder types: Industry

Identifiers

NCT01194245

HALO-117-205

Details and patient eligibility

About

The purpose of the study is to compare Humalog (Insulin lispro)-recombinant human hyaluronidase (rHuPH20) or Novolog (Insulin aspart)-rHuPH20 to Humalog (Insulin lispro) for the treatment of Type 1 Diabetes Mellitus (T1DM) in basal-bolus therapy.

Full description

Criteria for randomization into the study included 1) fasting blood glucose and predinner 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 completed 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.

Enrollment: 135 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Males or females aged ≥18 years
• Type 1 Diabetes Mellitus (T1DM) treated with insulin for ≥12 months
• Body mass index (BMI) 18.0 to 40.0 kilograms per square meter (kg/m^2).
• Hemoglobin A1C (HbA1C) level 6.7% to 8.2%, inclusive
• Fasting C-peptide <0.6 nanograms per milliliter (ng/mL)
• Willingness to use twice daily (BID) insulin glargine 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
• Use of pramlintide within 30 days of Screening
• Use of drugs during the study or within 30 days of Screening (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
• Recurrent severe hypoglycemia (more than 2 episodes over the last 6 months) or hypoglycemic unawareness, as judged by the Investigator

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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135 participants in 2 patient groups

Lispro-PH20 / Insulin Lispro

Experimental group

Description:

All enrolled participants underwent a titration period of 4-6 weeks in which they received 100 units per milliliter (U/mL) insulin glulisine, injected subcutaneously (SC), pre-meals, with doses titrated to each participant individually. Next participants were randomly assigned to 1 of 2 study treatments (Treatment A or B) for the first of two, 3-month treatment cycles. Each participant then received the second treatment for the second cycle with no washout period. Lispro-PH20 (Treatment A): 100 U/mL insulin lispro with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected SC, pre-meals, with doses titrated to each participant individually Insulin Lispro (Treatment B): 100 U/mL insulin lispro, injected SC, pre-meals, with doses titrated to each participant individually Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine.

Treatment:

Drug: Insulin glulisine

Drug: recombinant human hyaluronidase PH20

Drug: Insulin glargine

Drug: Insulin lispro

Aspart-PH20 / Insulin Lispro

Experimental group

Description:

All enrolled participants underwent a titration period of 4-6 weeks in which they received 100 units per milliliter (U/mL) insulin glulisine, injected subcutaneously (SC), pre-meals, with doses titrated to each participant individually. Next participants were randomly assigned to 1 of 2 study treatments (Treatment A or B) for the first of two, 3-month treatment cycles. Each participant then received the second treatment for the second cycle with no washout period. Aspart-PH20 (Treatment A): 100 U/mL insulin aspart with 5.0 micrograms per milliliter (µg/mL) recombinant human hyaluronidase PH20, injected SC, pre-meals, with doses titrated to each participant individually Insulin Lispro (Treatment B): 100 U/mL insulin lispro, injected SC, pre-meals, with doses titrated to each participant individually Throughout the study, participants requiring basal insulin used twice daily SC injections of 100 U/mL insulin glargine.

Treatment:

Drug: Insulin glulisine

Drug: recombinant human hyaluronidase PH20

Drug: Insulin glargine

Drug: Insulin aspart

Drug: Insulin lispro