Randomized, Double Blind, 2 Way Crossover Study of CSII With, Versus Without, Pretreatment With Human Hyaluronidase

Halozyme

Status and phase: Completed; Phase 4

Conditions: Type 1 Diabetes Mellitus

Treatments: Drug: Insulin lispro; Drug: Insulin aspart; Drug: Recombinant human hyaluronidase PH20; Drug: Sham Injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT01526733

Halo-117-401

Details and patient eligibility

About

The purpose of this study is to evaluate consistency of accelerated insulin absorption and onset-of-action and shortened duration of action for bolus insulin infusions after pretreatment with 150 units (U) of Hylenex® (recombinant human hyaluronidase PH20 [rHuPH20]) injection at the time of infusion set insertion compared to sham injection.

Enrollment: 25 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Males or females 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.
2. Non-smoking participants with Type 1 diabetes mellitus (T1DM) treated with insulin for ≥12 months. Nonsmoking means abstinence from cigarettes and cigars for 3 months and negative cotinine screening tests at screening.
3. Body mass index (BMI) 18.0 to 35.0 kilograms per meter squared (kg/m²), inclusive.
4. Glycosylated hemoglobin A1c (HbA1c) ≤10% based on local laboratory results.
5. Fasting connecting peptide of insulin (C-peptide) <0.6 nanograms per milliliter (ng/mL).
6. Current treatment with insulin <90 units per day (U/d).
7. Current use of rapid acting insulin analog.
8. Routine use of CSII as the primary route of insulin administration for at least 3 months prior to screening
9. Participants 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 the study protocol.

Exclusion criteria

1. Known or suspected allergy to any component of any of the study drugs in this study.
2. Previous enrollment in this study.
3. Use of drugs 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. Participants taking maintenance doses of blood thinners (for example, coumadin or heparin) will be excluded.
4. Use of any long-acting insulin injection within 72 hours of Study Day 1; participants will continue to refrain from use throughout the duration of the study (Phases I and II).
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 the Screening Visit(s) in this study.
8. Pregnancy, breastfeeding, 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 Study Day 1.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Triple Blind

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25 participants in 2 patient groups

Insulin (Aspart or Lispro)-Sham

Sham Comparator group

Description:

In Phase I or Phase II of the study, participants received 0.15 units per kilogram (U/kg) insulin (either insulin aspart or insulin lispro) as a continuous subcutaneous insulin infusion (CSII) for 16 days, with sham injections administered prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16. Each Phase was separated by a washout period of 5 to 21 days.

Treatment:

Drug: Insulin aspart

Drug: Sham Injection

Drug: Insulin lispro

Insulin (Aspart or Lispro)-rHuPH20

Experimental group

Description:

In Phase I or Phase II of the study, participants received 0.15 U/kg insulin (either insulin aspart or insulin lispro) as a CSII for 16 days. Prior to outpatient euglycemic clamps on Days 1 and 4 and prior to outpatient meal test procedures on Days 7, 10, 13, and 16, participants received a 1 mL (150 U) injection of recombinant human hyaluronidase (rHuPH20). Each Phase was separated by a washout period of 5 to 21 days.

Treatment:

Drug: Recombinant human hyaluronidase PH20

Drug: Insulin aspart

Drug: Insulin lispro