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Randomized, Double-blind, Crossover, PK and GD Study of CSII in Subjects With Type 1 Diabetes

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by:
Halozyme Therapeutics
ClinicalTrials.gov Identifier:
NCT01275131
First received: January 10, 2011
Last updated: March 6, 2012
Last verified: May 2011
History of Changes
  Purpose

The purpose of this study is to determine if rHuPH20 will change the exposure and action of approved insulin analogs when given by continuous subcutaneous infusion in people with Type 1 diabetes.


Condition Intervention Phase
Type 1 Diabetes Mellitus
 Drug: Insulin aspart alone
Drug: insulin aspart with rHuPH20
Drug: Insulin glulisine alone
Drug: Insulin glulisine with rHuPH20
 Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Official Title: Randomized, Double-Blind, Pharmacokinetic (PK) and Glucodynamic (GD) Crossover Study of Continuous Subcutaneous Insulin Infusion (CSII) of Rapid Acting Insulin Analogs With and Without Recombinant Human Hyaluronidase (rHuPH20)

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Halozyme Therapeutics:

Primary Outcome Measures:
  • Pharmacokinetic percent of area under the curve (PK% AUC) [ Time Frame: 0 to 60 minutes ] [ Designated as safety issue: No ]
    Based on serum insulin concentrations collected at specified time points, compare PK %AUC0-60 for insulin analogs with and without rHuPH20.


Secondary Outcome Measures:
  • Determine and compare glucodynamic responses [ Time Frame: 72 hours ] [ Designated as safety issue: No ]
    Determine and compare various GD responses (including tmax, Early and Late tGIR50%max, GIRmax, time to various % of total glucose infused increments, and fractional and absolute total glucose infused at various time intervals), based on glucose infusion rates (GIR) over time for each study treatment.


Estimated Enrollment: 36
Study Start Date: December 2010
Estimated Study Completion Date: July 2012
Estimated Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Insulin aspart alone
Insulin aspart alone as a continuous subcutaneous insulin infusion in subjects with Type 1 diabetes.
 Drug: Insulin aspart alone
Administered SC by a continuous infusion in the abdominal wall. Infusions will be delivered with a 6mm (thin subjects) or 9mm (all other subjects) catheter with a 90 degree entry angle placed in the lower abdominal area.
Experimental: Insulin aspart with rHuPH20
Insulin aspart as a continuous subcutaneous insulin infusion in subjects with Type 1 diabetes.
 Drug: insulin aspart with rHuPH20
Administered SC by a continuous infusion in the abdominal wall. Infusions will be delivered with a 6mm (thin subjects) or 9mm (all other subjects) catheter with a 90 degree entry angle placed in the lower abdominal area.
Active Comparator: Insulin glulisine alone
Insulin glulisine as a continuous subcutaneous insulin infusion in subjects with Type 1 diabetes.
 Drug: Insulin glulisine alone
Administered SC by a continuous infusion in the abdominal wall. Infusions will be delivered with a 6mm (thin subjects) or 9mm (all other subjects) catheter with a 90 degree entry angle placed in the lower abdominal area.
Experimental: Insulin glulisine with rHuPH20
Insulin glulisine as a continuous subcutaneous insulin infusion in subjects with Type 1 diabetes.
 Drug: Insulin glulisine with rHuPH20
Administered SC by a continuous infusion in the abdominal wall. Infusions will be delivered with a 6mm (thin subjects) or 9mm (all other subjects) catheter with a 90 degree entry angle placed in the lower abdominal area.

Detailed Description:

Previous clinical studies of insulin coadministered with rHuPH20 have demonstrated insulin pharmacokinetics (PK) that better replicate the natural insulin response to a meal in healthy individuals. Specifically, coadministration of insulin with rHuPH20 accelerates the onset of insulin action (early t50% max), the time of peak insulin concentration (tmax), and the offset of insulin action (late t50%max). rHuPH20 coadministration also increases the peak insulin concentration, increases early insulin exposure, and reduces late postprandial insulin exposure. In healthy volunteers, this acceleration of insulin exposure results in accelerated glucose metabolism, as measured by glucose infusion rates during a euglycemic clamp. In subjects with Type 1 and Type 2 diabetes mellitus, the acceleration of insulin exposure has been shown to reduce postprandial hyperglycemia, as measured by peak blood glucose, two-hour postprandial glucose, and total area of glucose excursions >140 mg/d occurring in response to a standardized liquid test meal.

This study is designed to compare the PK of insulin analogs when they are infused with and without rHuPH20. In addition to comparisons of various PK and glucodynamic measures, safety and tolerability of insulin analogs alone and with rHuPH20 during continuous infusion of each study drug in subjects with Type 1 diabetes mellitus will be evaluated.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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. Body mass index (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. Routine use of CSII as the primary route of insulin administration.
  8. 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 (Exception: subjects 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. 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 Visit 1, 2, 4, or 5.
  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. This applies both to new subjects and to subjects 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 Visit 1 (Stage 1) or Visit 4 (Stage 2) in this study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01275131

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:
Sponsor website  This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party: Linda Morrow, MD - Principal Investigator, Profil Institute for Clinical Research, Inc.
ClinicalTrials.gov Identifier: NCT01275131     History of Changes
Other Study ID Numbers: HALO-117-105
Study First Received: January 10, 2011
Last Updated: March 6, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Halozyme Therapeutics:
Insulin analog
Type 1 diabetes mellitus
Pharmacokinetic
Glucodynamic
Phase 1

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

ClinicalTrials.gov processed this record on October 18, 2012