Overview

This trial is active, not recruiting.

Condition type 1 diabetes mellitus
Treatments insulin aspart alone, insulin aspart with rhuph20, insulin glulisine alone, insulin glulisine with rhuph20
Phase phase 1
Sponsor Halozyme Therapeutics
Start date December 2010
End date May 2012
Trial size 36 participants
Trial identifier NCT01275131, HALO-117-105

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification pharmacokinetics/dynamics study
Intervention model crossover assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose basic science
Arm
(Active Comparator)
Insulin aspart alone as a continuous subcutaneous insulin infusion in subjects with Type 1 diabetes.
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 as a continuous subcutaneous insulin infusion in subjects with Type 1 diabetes.
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 as a continuous subcutaneous insulin infusion in subjects with Type 1 diabetes.
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 as a continuous subcutaneous insulin infusion in subjects with Type 1 diabetes.
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.

Primary Outcomes

Measure
Pharmacokinetic percent of area under the curve (PK% AUC)
time frame: 0 to 60 minutes

Secondary Outcomes

Measure
Determine and compare glucodynamic responses
time frame: 72 hours

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

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.

Additional Information

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)
Principal investigator Linda Morrow, MD
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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2012.
Information provided to ClinicalTrials.gov by Halozyme Therapeutics.