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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Halozyme Therapeutics
ClinicalTrials.gov Identifier:
NCT01526733
First received: January 31, 2012
Last updated: September 23, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Type 1 Diabetes Mellitus
Drug: Sham Injection
Drug: Recombinant human hyaluronidase PH20
Drug: Insulin aspart
Drug: Insulin lispro
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Halozyme Therapeutics:

Primary Outcome Measures:
  • Early Insulin Exposure (%AUC[0-60]) [ Time Frame: 10 minutes predose up to 60 minutes postdose on Days 1 and 4 ] [ Designated as safety issue: No ]
    Early insulin exposure, defined as the percentage of total insulin exposure (area under the insulin concentration curve [AUC{0 360}]) that occurs within the first hour following bolus dose of insulin during the 2 euglycemic clamps is presented. Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.


Secondary Outcome Measures:
  • Maximum Glucose Infusion Rate (GIRmax) [ Time Frame: 0 up to 360 minutes postdose on Days 1 and 4 ] [ Designated as safety issue: No ]
    Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

  • Time to First Occurrence of Maximum Glucose Infusion Rate (tGIRmax) [ Time Frame: 0 up to 360 minutes postdose on Days 1 and 4 ] [ Designated as safety issue: No ]
    Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

  • Time to 50% Maximum Glucose Infusion Rate (tGIR50%Max) [ Time Frame: 0 up to 360 minutes postdose on Days 1 and 4 ] [ Designated as safety issue: No ]
    Early and late tGIR50%max are presented. Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

  • Time to 50% Total Glucose Infused (50%Gtot) [ Time Frame: 0 up to 360 minutes postdose on Days 1 and 4 ] [ Designated as safety issue: No ]
    Blood samples were collected at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

  • Area Under the Glucose Concentration Curve (AUC[0-360]) [ Time Frame: 30 minutes predose up to 360 minutes postdose Days 1 and 4 ] [ Designated as safety issue: No ]
    Area under the glucose concentration curve from 0 to 360 minutes (AUC[0-360]) is presented. Blood samples were collected 30 and 10 minutes prior to insulin bolus and at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.

  • Duration of Insulin Action (AUMC[0-360]/AUC[0-360]) [ Time Frame: 10 minutes predose up to 360 minutes postdose on Days 1 and 4 ] [ Designated as safety issue: No ]
    Duration of insulin action was calculated by dividing the area under the first moment curve (AUMC[0-360]) by the area under the concentration versus time curve (AUC[0-360]). Blood samples were collected 10 minutes predose and at 0, 5, 10, 15, 20, 30, 45, 60, 90, 120, 150, 180, 240, 300, and 360 minutes postdose during a euglycemic clamp.


Enrollment: 25
Study Start Date: December 2011
Study Completion Date: September 2013
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sham Comparator: Insulin (Aspart or Lispro)-Sham

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.

Drug: Sham Injection Drug: Insulin aspart
Other Names:
  • Novolog
  • Aspart
Drug: Insulin lispro
Other Names:
  • Humalog
  • Lispro
Experimental: Insulin (Aspart or Lispro)-rHuPH20

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.

Drug: Recombinant human hyaluronidase PH20
Other Names:
  • rHuPH20
  • PH20
  • Hylenex
Drug: Insulin aspart
Other Names:
  • Novolog
  • Aspart
Drug: Insulin lispro
Other Names:
  • Humalog
  • Lispro

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01526733

Locations
United States, California
Profil Institute for Clinical Research
Chula Vista, California, United States, 91911
Sponsors and Collaborators
Halozyme Therapeutics
Investigators
Principal Investigator: Linda Morrow, MD Profil Institute for Clinical Research, Inc.
  More Information

Additional Information:
No publications provided

Responsible Party: Halozyme Therapeutics
ClinicalTrials.gov Identifier: NCT01526733     History of Changes
Other Study ID Numbers: Halo-117-401
Study First Received: January 31, 2012
Results First Received: September 23, 2014
Last Updated: September 23, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Halozyme Therapeutics:
Type 1 Diabetes
Continuous Subcutaneous Insulin Infusion (CSII)

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Autoimmune Diseases
Endocrine System Diseases
Glucose Metabolism Disorders
Immune System Diseases
Metabolic Diseases
Insulin
Insulin Aspart
Insulin Lispro
Insulin, Globin Zinc
Hypoglycemic Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on November 25, 2014