Pharmacokinetic (PK), Pharmacodynamic (PD), and Safety Study of Subcutaneously Administered Humalog® With and Without Recombinant Human Hyaluronidase (rHuPH20)and Humulin-R® With and Without rHuPH20
Condition: Diabetes Mellitus
Intervention: Humalog; Humulin-R; Recombinant human hyaluronidase PH20 (rHuPH20)
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Lispro
Phase: Phase 1
Study type: Interventional
Primary purpose: Health Services Research
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Enrollment: 26.0
Sex: Male
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: rHuPH20; Hyaluronidase; Insulin

Summary:

      The purpose of the study is to compare the pharmacokinetics (PK) and pharmacodynamics (PD) of
      Humalog (insulin lispro) or Humulin-R (recombinant human insulin) when administered as a
      single subcutaneous (SC) injection of 20 units (U) with or without coadministration of
      recombinant human hyaluronidase PH20 (rHuPH20).

      The study hypothesizes that the time required to reach maximum insulin concentration (tmax)
      when insulin is administered with rHuPH20 will be comparable or shorter than the time
      required without rHuPH20.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Healthy male participants aged 18 to 55 years.

          2. Body mass index (BMI) 18 to 28 kilograms per meter squared (kg/m^2) and total body
             weight >70 kilograms (kg) (154 pounds [lb]).

          3. Willingness and ability to comply with the protocol.

          4. Vital signs within the normal range.

          5. Within 7 days before the first injection, metabolic panel results and complete blood
             count (CBC) within the laboratory normal reference range.

          6. Fasting plasma glucose within the normal range of 90 to 110 milligrams per deciliter
             (mg/dL) on the morning of the glucose clamp.

          7. Agreement not to father a child or donate sperm and to use effective contraception
             during the study and for at least 30 days after study completion.

          8. Willingness and ability to sign an informed consent form.

        Exclusion Criteria:

          1. Evidence or history of clinically significant hematologic, renal, endocrine,
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic (to
             include history of seizures) or allergic disease, or history of hypoglycemic episodes.

          2. Known history of diabetes mellitus.

          3. Prior exposure to any insulin or insulin analogs.

          4. Known allergy to hyaluronidase or any other ingredient in HYLENEX.

          5. Known allergy to bee or vespid venom.

          6. Positive urine drug screen results.

          7. Positive human immunodeficiency virus (HIV) 1, HIV 2, hepatitis B, or hepatitis C
             antibody test result.

          8. Any history or evidence of alcohol or drug abuse.

          9. History or evidence of use of any tobacco- or nicotine-containing product within 6
             months of screening, or screening urine nicotine concentration >50 nanograms per
             milliliter (ng/mL).

         10. Use of prescription or nonprescription drugs within 7 days or 5 half-lives, whichever
             was shorter, except acetaminophen at doses of less than or equal to 1 gram per day
             (g/day).

         11. Donation of blood in excess of 500 milliliters (mL) within 56 days before dosing.

         12. Failure to limit alcohol consumption and refrain from exercise within 48 hours before
             each injection.

         13. Known clinically significant intercurrent illness or other major systemic disease that
             would unduly risk the participant's safety or interfere with the interpretation of
             results.

         14. Participation in a study of any investigational drug or device 30 days before
             enrollment in this study.

         15. Unfitness for the study, in the investigator's opinion.