Pharmacokinetic and Glucodynamic Crossover Study of Subcutaneously (SC) Administered Insulin Lispro + Recombinant Human Hyaluronidase (rHuPH20) and Regular Human Insulin + rHuPH20 Compared to Insulin Lispro Alone
Condition: Diabetes Mellitus
Intervention: Insulin Lispro; Regular Human Insulin; rHuPH20
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Lispro
Phase: Phase 1
Study type: Interventional
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 22.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: rHuPH20; Recombinant Human Hyaluronidase; Insulin Lispro; Regular Human Insulin

Summary:

      Insulin lispro and regular human insulin are Food and Drug Administration (FDA)-approved
      medications 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 will be co-administered with both insulin lispro and regular human
      insulin in order to determine if it improves the absorption of these insulins to more closely
      mimic the body's natural increase in insulin in response to a meal.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy participants between the ages of 18 and 55 years, inclusive. (Healthy is
             defined as no clinically relevant abnormalities.)

          -  Body mass index (BMI) between 18-27 kilograms per meter squared (kg/m^2), inclusive.

          -  Total body weight >65 kilograms (kg) (143 pounds [lb]) for men and >46 kg (101 lb) for
             women.

          -  Decision making capacity and willingness to comply with scheduled visits, treatment
             plan, laboratory tests, and other study procedures including adequate venous access.

          -  Vital signs (blood pressure, pulse rate, body temperature) within normal range or, if
             out of range, assessed by the Principal Investigator (PI) as not clinically
             significant (NCS).

          -  Fasting blood glucose level <100 milligrams per deciliter (mg/dL) at screening.

          -  A negative serum pregnancy test (if female of childbearing potential).

          -  Female participants of childbearing potential must agree to be practicing effective
             birth control or abstinence currently and agree to continue to do so for the duration
             of their time on study.

          -  Signed, written Institutional Review Board (IRB)-approved informed consent.

        Exclusion Criteria:

          -  Evidence or history of clinically significant hematological, renal, endocrine,
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, oncologic, or
             neurologic (to include history of seizures) disease; hypoglycemic episodes;
             intercurrent illness (such as influenza); or allergic disease (including severe drug
             allergies, but excluding untreated, asymptomatic, seasonal allergies at time of
             dosing). Clinical significance to be determined by the PI.

          -  As judged by the Investigator, clinically significant findings in routine laboratory
             data. (Anemia with hematocrit less than 33% at screening is specifically
             exclusionary.)

          -  Known history of diabetes mellitus (type 1 or type 2) or gestational diabetes.

          -  Known allergy to hyaluronidase or any other ingredient in the study drug.

          -  Positive human immunodeficiency virus (HIV 1) antibody test, hepatitis B
             (anti-hepatitis B surface antigen [anti-HBsAg]) or hepatitis C (anti-hepatitis C virus
             [anti-HCV]) antibody test.

          -  History or evidence of alcohol or drug abuse.

          -  History or evidence of use of any tobacco or nicotine-containing product within 6
             months of screening and a screening qualitative urine nicotine test.

          -  Use of drugs that may interfere with the interpretation of trial results or are known
             to cause clinically relevant interference with insulin action or glucose utilization.

          -  Donation of blood in excess of 500 milliliters (mL) within 56 days before dosing.

          -  Participation in a study of any investigational drug or device 30 days before
             enrollment in this study.

          -  The participant is unfit for the study in the opinion of the Investigator.

          -  Women who are pregnant or breast-feeding.