A Pharmacokinetic and Glucodynamic Study of Subcutaneously Administered Insulin Analogs With rHuPH20 Compared to Insulin Analogs Alone
Condition: Healthy
Intervention: Recombinant human hyaluronidase PH20 (rHuPH20); Insulin lispro; Insulin glulisine; Insulin aspart
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin Lispro; Insulin glulisine
Phase: Phase 1
Study type: Interventional
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: insulin; recombinant human hyaluronidase; Healthy volunteers

Summary:

      This is a single-center, Phase 1, randomized, double-blind, 6-way crossover study to
      determine insulin pharmacokinetics, insulin glucodynamics, safety, and tolerability of
      subcutaneously administered dose(s) of insulin lispro + recombinant human hyaluronidase PH20
      (rHuPH20), insulin lispro alone, insulin glulisine + rHuPH20, insulin glulisine alone,
      insulin aspart + rHuPH20, and insulin aspart alone.
    

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 [BP], pulse rate, body temperature) within normal range
             or, if out of range, assessed by the Principal Investigator as not clinically
             significant.

          -  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 practice 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 Principal Investigator.

          -  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, hepatitis B, or hepatitis C 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 prior to screening and a screening qualitative urine nicotine test.

          -  Use of drugs that may interfere with the interpretation of study results or are known
             to cause clinically relevant interference with insulin action or glucose utilization.

          -  Blood donation or high volume phlebotomy, for example, >100 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.