Safety Study of Subcutaneously-Injected Prandial INSULIN-PH20 NP Compared to Insulin Lispro Injection in Participants With Type 1 Diabetes Mellitus
Condition: Diabetes Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Insulin Lispro; regular human insulin; recombinant human hyaluronidase PH20; Insulin glargine
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Glargine; Insulin Lispro
Phase: Phase 2
Study type: Interventional
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 48.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: recombinant human hyaluronidase (rHuPH20); Insulin lispro; regular human insulin

Summary:

      Insulin lispro is approved by the Food and Drug Administration (FDA) for the treatment of
      diabetes mellitus. Recombinant human hyaluronidase (rHuPH20) is approved by the FDA as an aid
      to the absorption and dispersion of other injectable drugs. In this study, rHuPH20 combined
      with a non-preserved (NP) formulation of regular human insulin (INSULIN-PH20 NP) will be
      compared to insulin lispro with respect to absorption and action of insulin.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female of age 18 to 65 years, inclusive. Females of child-bearing potential
             must use a standard and effective means of birth control for the duration of the
             study.

          -  Participants with Type 1 diabetes mellitus (T1DM) (per World Health Organization [WHO]
             criteria) treated with insulin for ≥24 months.

          -  Participants who use an insulin infusion pump for basal insulin administration must be
             on the device for at least 90 days prior to screening.

          -  Body mass index (BMI) 18.0 to 35.0 kilograms per square meter (kg/m^2), inclusive.

          -  Glycosylated hemoglobin A1c (HbA1c) ≤7.5 % based on central laboratory screening
             results.

          -  Fasting C-peptide <0.6 nanograms per milliliter (ng/mL).

          -  Participants should be in good general health based on medical history and physical
             examination and without medical conditions that might prevent the completion of study
             drug injections and assessments required in this protocol.

        Exclusion Criteria:

          -  Known or suspected allergy to any component of any of the study drugs in this study.

          -  Previous enrollment in this study. Participants who fail Screening may attempt to
             rescreen into the study.

          -  A participant who has proliferative retinopathy or 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 electrocardiogram [ECG]), hepatic, neurological, renal, genitourinary, or
             hematological systems.

          -  As judged by the Investigator, uncontrolled hypertension (diastolic blood pressure
             ≥100 millimeters of mercury [mmHg] and/or systolic blood pressure ≥160 mmHg after 5
             minutes in the supine position). Three attempts may be performed to measure blood
             pressure.

          -  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.

          -  As judged by the Investigator, clinically significant findings in routine laboratory
             data.

          -  Use of drugs (such as systemic corticosteroids) 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 severe hypoglycemia (more than 2 episodes over the last 6 months) or
             hypoglycemic unawareness, as judged by the Investigator.

          -  Current addiction to alcohol or substances of abuse, as determined by the
             Investigator.

          -  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, or barrier methods).

          -  Mental incapacity, unwillingness, or language barriers precluding adequate
             understanding or cooperation in this study.

          -  Receipt of any investigational drug within 4 weeks of Screening.

          -  Any condition (intrinsic or extrinsic) that in the judgment of the Investigator will
             interfere with study participation or evaluation of data. Examples would include:
             renal insufficiency (serum creatinine >1.5 milligrams per deciliter [mg/dL] for males
             or >1.4 mg/dL for females), congestive heart failure required medication treatment,
             and cardiac disease with New York Heart Association (NYHA) Functional Capacity of
             III/IV.