Clinical trial NCT01526733: Randomized, Double Blind, 2 Way Crossover Study of CSII With, Versus Without, Pretreatment With Human Hyaluronidase
Official title: A Phase 4, Randomized, Double-Blind, 2-Way Crossover Study of Continuous Subcutaneous Insulin Infusion (CSII) With, Compared to Without, Pretreatment With Recombinant Human Hyaluronidase (rHuPH20)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 1 Diabetes Mellitus
Keywords: Type 1 Diabetes
Continuous Subcutaneous Insulin Infusion (CSII)
Lead sponsor: Halozyme Therapeutics
Sponsor class: INDUSTRY
First posted: 2012-02-06
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Early Insulin Exposure (%AUC[0-60])
timeFrame: 10 minutes predose; 0, 5, 10, 15, 20, 30, 45, and 60 minutes postdose on Days 1 and 4
Secondary outcomes:
measure: Maximum Glucose Infusion Rate (GIRmax)
timeFrame: 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
measure: Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax)
timeFrame: 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
measure: Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max)
timeFrame: 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
measure: Time to 50% Total Glucose Infused (50%Gtot)
timeFrame: 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
measure: Area Under the Glucose Concentration Curve (AUC[0-360])
timeFrame: 30 minutes and 10 minutes predose; 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
measure: Duration of Insulin Action (AUMC[0-360]/AUC[0-360])
timeFrame: 10 minutes predose; 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose on Days 1 and 4
Other outcomes:
Locations:
city: Chula Vista
country: United States
facility: Profil Institute for Clinical Research
state: California
Study officials:
affiliation: Profil Institute for Clinical Research, Inc.
name: Linda Morrow, MD
role: PRINCIPAL_INVESTIGATOR
References: