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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Halozyme Therapeutics
ClinicalTrials.gov Identifier:
NCT01526733
First received: January 31, 2012
Last updated: July 10, 2013
Last verified: August 2012
  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 U of Hylenex® recombinant (hyaluronidase human injection)(rHuPH20) at the time of infusion set insertion compared to sham injection.


Condition Intervention Phase
Type 1 Diabetes Mellitus
Device: Sham Injection
Drug: Rapid Acting insulin with pre-treatment of rHuPH20
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:
  • Insulin absorption assessed by the amount of insulin exposure within the first hour following bolus insulin infusion. [ Time Frame: 0-60 minutes ] [ Designated as safety issue: No ]
    The primary endpoint will be insulin absorption as assessed by the amount of insulin exposure within the first one hour following bolus insulin infusion expressed as a fraction of the total insulin exposure during the six hour euglycemic clamp.


Secondary Outcome Measures:
  • Glycemic Excursions with and without pre-treatment with Hylenex recombinant. [ Time Frame: 72 Hours ] [ Designated as safety issue: No ]
    Demonstrate reduced glycemic excursions, greater proportions of subjects reaching postprandial clinical targets, safety, tolerability of the SC infusion of rapid acting insulin with and without pre-treatment with Hylenex recombinant.

  • Changes in insulin absorption with and without pre-treatment with Hylenex recombinant. [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Demonstrate changes in insulin absorption, safety, tolerability of the SC infusion of rapid acting insulin with and without pre-treatment with Hylenex recombinant.


Enrollment: 25
Study Start Date: December 2011
Estimated Study Completion Date: September 2013
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Sham Comparator: Continuous Subcutaneous Insulin Infusion

Rapid Acting insulin alone as a Continuous Subcutaneous Insulin Infusion in subjects with Type 1 diabetes.

Intervention: Sham Injection

Device: Sham Injection
Sham will be delivered via direct injection into the infusion set catheter placed in the lower abdominal area
Experimental: Rapid acting insulin with pre-treatment of rHuPH20

Rapid acting insulin as a Continuous Subcutaneous Insulin Infusion in subjects with Type 1 diabetes.

Intervention: Rapid acting insulin with pre-treatment of rHuPH20

Drug: Rapid Acting insulin with pre-treatment of rHuPH20
Administered SC by a continuous infusion in the abdominal wall. Injections will be administered directly in the lower abdominal area
Other Name: Hylenex

Detailed Description:

There is a recognized need for more rapid insulin action than is available from current rapid acting analog products. In addition, current products have inconstant absorption and action profiles over the course of infusion set life. Previous human studies of prandial insulin preparations have used co-mixtures of rHuPH20 (study drug) with insulin delivered to study subjects by subcutaneous injection and have demonstrated acceleration of insulin absorption and action. Continuous subcutaneous insulin infusion (CSII) has been used clinically for the treatment of diabetes over the last three decades, and a previous study using a co-mixture of rHuPH20 during CSII showed that the combination resulted in a more consistent and ultrafast profile of insulin absorption and action across infusion set use as compared to rapid analog insulin alone. The present study will evaluate the ability of rHuPH20 pretreatment to confer a consistent ultrafast profile of absorption and action to rapid analog insulin products across the life of infusion sets.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female 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 subjects with Type 1 diabetes mellitus treated with insulin for ≥12 months. Nonsmoking means abstinence from cigarettes and cigars for 3 months and negative cotinine screening tests at screening.
  3. BMI 18.0 to 35.0 kg/m², inclusive.
  4. HbA1c (glycosylated hemoglobin A1c) ≤ 10 % based on local laboratory results.
  5. Fasting C-peptide < 0.6 ng/mL.
  6. Current treatment with insulin < 90 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 three months prior to screening
  9. Subject 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
  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. Subjects taking maintenance doses of blood thinners (e.g. Coumadin or heparin) will be excluded.
  4. Use of any long acting insulin injection within 72 hours of Study Day 1 continuing to refrain from use throughout the duration of the study, Phases 1 and 2.
  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 mL) within the previous 8 weeks of the Screening Visit(s) in this study.
  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 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
Last Updated: July 10, 2013
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
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 22, 2014