CONSISTENT 1: Metabolic and Safety Outcomes of Hylenex Recombinant (Hyaluronidase Human Injection) Preadministered at CSII Infusion Site in Participants With Type 1 Diabetes Mellitus (T1DM)
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Commercial Hylenex® recombinant (hyaluronidase human injection); Precommercial Hylenex recombinant (hyaluronidase human injection); Insulin lispro; Insulin aspart; Insulin glulisine
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin Lispro; Insulin glulisine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Enrollment: 456.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Type 1 Diabetes Mellitus; Sub Cutaneous Insulin Infusion; Rapid Acting Analog Insulin; Hylenex; Halozyme; Phase 4

Summary:

      The primary objectives of this study are to compare the difference in glycosylated hemoglobin
      (HbA1c) from baseline to Month 6 using Hylenex recombinant preadministration in continuous
      subcutaneous insulin infusion (CSII) versus standard CSII and to evaluate the safety of
      Hylenex recombinant preadministration, including local tolerability, adverse events, and
      hypo- and hyperglycemia rates.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female of age 18 years or older with a history of T1DM for at least 12 months

          2. Glycosylated hemoglobin (HbA1c) 6.5% to 9.5% (inclusive) based on central laboratory
             results

          3. Fasting C-peptide <0.6 nanograms per milliliter (ng/mL)

          4. Current use of an insulin pump compatible with available tubing for Hylenex
             recombinant infusion and use of an infusion set compatible with the tubing available
             or willingness to switch to an infusion set compatible with tubing available for
             infusion of Hylenex recombinant

          5. Current treatment at the time of screening with insulin <300 units per day (U/day)

          6. Participants who routinely use continuous glucose monitoring (CGM) (defined as average
             CGM use 5 or more days per week over the preceding 3 months) and those who do not
             routinely used CGM are both eligible for inclusion in the study. Intermittent use of
             CGM is also acceptable but will not be a criterion use for stratified randomization.

          7. Participants should be in good general health based on medical history and physical
             examination, without medical conditions that might prevent the completion of study
             drug infusions and assessments required in this protocol.

        Exclusion Criteria:

          1. Type 2 diabetes

          2. Known or suspected allergy to any component of any of the study drugs in this study

          3. Severe proliferative retinopathy or maculopathy, and/or gastroparesis, and/or severe
             neuropathy, in particular autonomic neuropathy, of such severity as to impede the
             participant's ability to comply with protocol procedures, as judged by the
             Investigator

          4. History of transmural myocardial infarction, congestive heart failure and uncontrolled
             hypertension (diastolic blood pressure [BP] consistently >100 millimeters of mercury
             [mmHg]) are exclusionary

          5. As judged by the Investigator, clinically significant active disease of the
             gastrointestinal, cardiovascular (including history of stroke, history of arrhythmia,
             or conduction delays on electrocardiogram [ECG]), hepatic, neurological, renal,
             genitourinary, pulmonary, or hematological systems of such severity as to impede the
             participant's ability to comply with protocol procedures

          6. History of any illness or disease that in the opinion of the Investigator might
             confound the results of the study or pose additional risk in administering the study
             drugs to the participant

          7. As judged by the Investigator, clinically significant findings in routine laboratory
             data at screening

          8. Use of drugs that may interfere with the interpretation of study results or are known
             to cause clinically relevant interference with hyaluronidase action, insulin action,
             glucose utilization, or recovery from hypoglycemia (including systemic pharmacologic
             corticosteroid). Use of pramlintide or a glucagon-like peptide [GLP]-1 receptor
             agonist is not exclusionary but participants using these agents will be subjected to
             stratified randomization. Use of aspirin (acetylsalicylic acid [ASA]) up to 325
             milligrams (mg)/day is not exclusionary but should be noted for analysis.

          9. Hypoglycemic unawareness of such severity as to impede the participant's ability to
             comply with protocol procedures, as judged by the Investigator.

         10. Current addiction to alcohol or substance abuse as determined by the Investigator.

         11. 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, and/or barrier
             methods). Abstinence alone is not considered an adequate contraceptive measure for the
             purposes of this study.

         12. Mental incapacity, unwillingness, or language barriers precluding adequate
             understanding or cooperation in this study