Randomized, Double-blind, Crossover, Pharmacokinetic (PK) and Glucodynamic (GD) Study of Continuous Subcutaneous Insulin Infusion (CSII) in Participants With Type 1 Diabetes Mellitus (T1DM)
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Insulin aspart; Recombinant human hyaluronidase PH20 (rHuPH20)
Intervention MeSH terms: Insulin Aspart
Phase: Phase 1
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Insulin analog; Type 1 diabetes mellitus; Pharmacokinetic; Glucodynamic; Phase 1

Summary:

      The purpose of this study is to determine if recombinant human hyaluronidase PH20 (rHuPH20)
      will change the exposure and action of approved insulin analogs when given by continuous
      subcutaneous insulin infusion (CSII) in participants with Type 1 diabetes mellitus (T1DM).

      This study is divided into Stage 1, 2, and 3. Stage 3 was started chronologically before
      Stage 2 and, prior to performing Stage 2, the Sponsor made the decision to terminate Stage 2.
      Stage 2 was not initiated due to a strategic business decision and termination was not based
      on safety or efficacy concerns. No participants were enrolled in Stage 2.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female aged 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.

          2. Non-smoking participants with Type 1 diabetes mellitus (T1DM) treated with insulin for
             greater than or equal to 12 months. Non-smoking means abstinence from cigarettes and
             cigars for 3 months and negative cotinine screening tests.

          3. Body mass index (BMI) 18.0 to 35.0 kilograms per meter squared (kg/m^2), inclusive.

          4. Glycosylated hemoglobin A1c (HbA1c) ≤10 % based on local laboratory results.

          5. Fasting C-peptide <0.6 nanograms per milliliter (ng/mL).

          6. Current treatment with insulin <90 units per day (U/d).

          7. Routine use of continuous subcutaneous insulin infusion (CSII) as the primary route of
             insulin administration.

          8. Participant 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. Known or suspected allergy to any component of any of the study drugs in this trial.

          2. Previous enrollment in this trial (Exception: participants in Stage 1 are permitted to
             participate in Stage 2).

          3. Use of drugs that may interfere with the interpretation of trial results or are known
             to cause clinically relevant interference with insulin action, glucose utilization, or
             recovery from hypoglycemia. Participants taking maintenance doses of blood thinners
             (eg, Coumadin or heparin) will be excluded.

          4. Use of any long-acting insulin injection within 72 hours of Stage 1 or Stage 3.

          5. Recurrent major hypoglycemia or hypoglycemic unawareness, as judged by the
             Investigator.

          6. Current addiction to alcohol or substances of abuse as determined by the Investigator.

          7. Blood donation or phlebotomy (>500 milliliters [mL]) within the previous 8 weeks of
             Screening. This applies both to new participants and to participants who have
             participated in Stage 1 and who wish to continue in Stage 2.

          8. 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).

          9. Symptomatic gastroparesis.

         10. Receipt of any investigational drug within 4 weeks of Stage 1 or Stage 2.