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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified May 2011 by Halozyme Therapeutics.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
Halozyme Therapeutics
ClinicalTrials.gov Identifier:
NCT01275131
First received: January 10, 2011
Last updated: March 6, 2012
Last verified: May 2011

January 10, 2011
March 6, 2012
December 2010
May 2012   (final data collection date for primary outcome measure)
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.
Pharmacokinetic percent of area under the curve [ 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.
Complete list of historical versions of study NCT01275131 on ClinicalTrials.gov Archive Site
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.
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 over time for each study treatment.
Not Provided
Not Provided
 
Randomized, Double-blind, Crossover, PK and GD Study of CSII in Subjects With Type 1 Diabetes
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)

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.

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.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Basic Science
Type 1 Diabetes Mellitus
  • 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.
  • 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.
  • 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.
  • 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.
  • Active Comparator: Insulin aspart alone
    Insulin aspart alone as a continuous subcutaneous insulin infusion in subjects with Type 1 diabetes.
    Intervention: Drug: Insulin aspart alone
  • Experimental: Insulin aspart with rHuPH20
    Insulin aspart as a continuous subcutaneous insulin infusion in subjects with Type 1 diabetes.
    Intervention: Drug: insulin aspart with rHuPH20
  • Active Comparator: Insulin glulisine alone
    Insulin glulisine as a continuous subcutaneous insulin infusion in subjects with Type 1 diabetes.
    Intervention: Drug: Insulin glulisine alone
  • Experimental: Insulin glulisine with rHuPH20
    Insulin glulisine as a continuous subcutaneous insulin infusion in subjects with Type 1 diabetes.
    Intervention: Drug: Insulin glulisine with rHuPH20
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
36
July 2012
May 2012   (final data collection date for primary outcome measure)

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.
Both
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01275131
HALO-117-105
No
Linda Morrow, MD - Principal Investigator, Profil Institute for Clinical Research, Inc.
Halozyme Therapeutics
Not Provided
Principal Investigator: Linda Morrow, MD Profil Institute for Clinical Research, Inc.
Halozyme Therapeutics
May 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP