Evaluation of Pharmacokinetics and Pharmacodynamic Properties of Rapid-Acting Insulin Analogs (PK/PD)
Primary Purpose
Diabetes Mellitus, Type I
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Insulin analogs (Lispro and Aspart)
Insulin analogs (Aspart and Detemir)
Insulin analogs (Aspart and Detemir)
Insulin analogs (Lispro and Glargine)
Insulin analogs (Lispro and Glargine)
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type I focused on measuring Type I Diabetes Mellitus
Eligibility Criteria
Inclusion Criteria:
- Age 8-17 (inclusive), of whom 15 will be prepubertal and 60 pubertal;
- Clinical diagnosis of T1D (based on clinical presentation, insulin dependence,and/or history of ketosis;
- Diagnosis of T1D for at least one year's duration;
- On CSII therapy for at least three months;
- HbA1c 6.5-8.0%, inclusive;
- Body mass index < 95% for age and gender;
- Meeting minimum weight requirement of at least 17.6 kg (for pre-pubertal subjects) or 34.6 kg (for pubertal subjects)
- Ability to comprehend written and spoken English
Exclusion Criteria:
- Any other medical disease aside from T1D or treated hypothyroidism
- Receiving any other medication besides insulin or levothyroxine
- Female subjects of reproductive potential who may be pregnant, breast feeding, or not consistently utilizing barrier methods or abstinence as contraception
- Inability to comprehend written and spoken English
- Any other condition, which in the judgement of the investigators, would interfere with the subject's or parents' ability to provide informed consent or the investigator's ability to perform the study
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Active Comparator
Active Comparator
Active Comparator
Active Comparator
Arm Label
Catheter day 4
Catheter day 1
Aspart and Detemir
Lispro and Glargine
Arm Description
Adolescents with type 1 diabetes with catheters day #4
Adolescents with type 1 diabetes with catheter day #1
Adolescents with type 1 diabetes
Adolescents with type 1 diabetes
Outcomes
Primary Outcome Measures
Maximum Glucose Infusion Rate (GIR) to maintain euglycemia
Secondary Outcome Measures
Time to Maximum Glucose Infusion Rate
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00652288
Brief Title
Evaluation of Pharmacokinetics and Pharmacodynamic Properties of Rapid-Acting Insulin Analogs
Acronym
PK/PD
Official Title
Evaluation of Pharmacokinetic and Pharmacodynamic Properties of Rapid-Acting Insulin Analogs Given as a Bolus by Continuous Subcutaneous Insulin Infusion (CSII) and in MDI Basal-Bolus Therapy in Pediatric Subjects With Type 1 Diabetes (TID)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
September 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Yale University
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The aim of this study is to evaluate the variations in pharmacokinetic and pharmacodynamic properties of rapid-acting insulin analogs when given as a bolus by subcutaneous insulin infusion pump as typically encountered in the care of children with type 1 diabetes.
The specific factors under investigation are:
the effects of puberty
type of insulin analog
site of catheter insertion
and age of catheter
Detailed Description
The aim of this study is to evaluate the variations in pharmacokinetic (as determined by serum free insulin concentrations) and pharmacodynamic (as determined by the glucose infusion rate required to maintain euglycemia during a euglycemic clamp) properties of the rapid acting insulin analogs when given as a bolus by subcutaneous insulin infusion pump as typically encountered in the care of children with type 1 diabetes. The specific factors we will investigate are the effects of puberty (pre- vs. pubertal), type of insulin analog (lispro or aspart insulin), site of catheter insertion (gluteal vs. abdominal), and age of catheter (fresh insertion vs. three-day duration) Our hypotheses are that the peak (Imax) and area under the curve (IAUC) serum free insulin concentration, and the peak glucose infusion rate required to maintain euglycemia (GIRmax) and area under the curve (GIRAUC) will vary based on these conditions, in children given the same weight-based dose.
We will also evaluate the pharmacokinetic and pharmacodynamic properties of Aspart and Lispro insulin when used in a basal-bolus regimen with insulin Detemir or Glargine, new basal insulin analogs, given as separate injections and when combined in a single injection in adolescent patients with Type 1 DM. We hypothesize that the peak (IMAX) and area under the curve (IAUC) serum insulin concentrations, and the peak glucose infusion rate required to maintain euglycemia (GIRMAX) and area under the curve (GIRAUC) of the Aspart/Lispro bolus, will be similar when the Aspart/Lispro is combined in the same syringe with the insulin Detemir/Glargine, compared to when the Aspart/Lispro and Detemir/Glargine are given as two separate injections.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type I
Keywords
Type I Diabetes Mellitus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Catheter day 4
Arm Type
Active Comparator
Arm Description
Adolescents with type 1 diabetes with catheters day #4
Arm Title
Catheter day 1
Arm Type
Active Comparator
Arm Description
Adolescents with type 1 diabetes with catheter day #1
Arm Title
Aspart and Detemir
Arm Type
Active Comparator
Arm Description
Adolescents with type 1 diabetes
Arm Title
Lispro and Glargine
Arm Type
Active Comparator
Arm Description
Adolescents with type 1 diabetes
Intervention Type
Drug
Intervention Name(s)
Insulin analogs (Lispro and Aspart)
Other Intervention Name(s)
Humalog, Novolog
Intervention Description
Insulin bolus given through insulin pump
Intervention Type
Drug
Intervention Name(s)
Insulin analogs (Aspart and Detemir)
Intervention Description
Drugs given separately
Intervention Type
Drug
Intervention Name(s)
Insulin analogs (Aspart and Detemir)
Intervention Description
Drugs given in the same injection
Intervention Type
Drug
Intervention Name(s)
Insulin analogs (Lispro and Glargine)
Intervention Description
Drugs given separately
Intervention Type
Drug
Intervention Name(s)
Insulin analogs (Lispro and Glargine)
Intervention Description
Drugs given in single injection
Primary Outcome Measure Information:
Title
Maximum Glucose Infusion Rate (GIR) to maintain euglycemia
Time Frame
Six hour observation period
Secondary Outcome Measure Information:
Title
Time to Maximum Glucose Infusion Rate
Time Frame
Six Hour Observation period
10. Eligibility
Sex
All
Minimum Age & Unit of Time
8 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 8-17 (inclusive), of whom 15 will be prepubertal and 60 pubertal;
Clinical diagnosis of T1D (based on clinical presentation, insulin dependence,and/or history of ketosis;
Diagnosis of T1D for at least one year's duration;
On CSII therapy for at least three months;
HbA1c 6.5-8.0%, inclusive;
Body mass index < 95% for age and gender;
Meeting minimum weight requirement of at least 17.6 kg (for pre-pubertal subjects) or 34.6 kg (for pubertal subjects)
Ability to comprehend written and spoken English
Exclusion Criteria:
Any other medical disease aside from T1D or treated hypothyroidism
Receiving any other medication besides insulin or levothyroxine
Female subjects of reproductive potential who may be pregnant, breast feeding, or not consistently utilizing barrier methods or abstinence as contraception
Inability to comprehend written and spoken English
Any other condition, which in the judgement of the investigators, would interfere with the subject's or parents' ability to provide informed consent or the investigator's ability to perform the study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stuart A Weinzimer, MD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Eda Cengiz, MD
Organizational Affiliation
Yale University
Official's Role
Principal Investigator
12. IPD Sharing Statement
Citations:
PubMed Identifier
22374642
Citation
Cengiz E, Swan KL, Tamborlane WV, Sherr JL, Martin M, Weinzimer SA. The alteration of aspart insulin pharmacodynamics when mixed with detemir insulin. Diabetes Care. 2012 Apr;35(4):690-2. doi: 10.2337/dc11-0732. Epub 2012 Feb 28.
Results Reference
result
PubMed Identifier
20150302
Citation
Cengiz E, Tamborlane WV, Martin-Fredericksen M, Dziura J, Weinzimer SA. Early pharmacokinetic and pharmacodynamic effects of mixing lispro with glargine insulin: results of glucose clamp studies in youth with type 1 diabetes. Diabetes Care. 2010 May;33(5):1009-12. doi: 10.2337/dc09-2118. Epub 2010 Feb 11.
Results Reference
result
PubMed Identifier
19017777
Citation
Swan KL, Dziura JD, Steil GM, Voskanyan GR, Sikes KA, Steffen AT, Martin ML, Tamborlane WV, Weinzimer SA. Effect of age of infusion site and type of rapid-acting analog on pharmacodynamic parameters of insulin boluses in youth with type 1 diabetes receiving insulin pump therapy. Diabetes Care. 2009 Feb;32(2):240-4. doi: 10.2337/dc08-0595. Epub 2008 Nov 18.
Results Reference
result
PubMed Identifier
17909083
Citation
Swan KL, Weinzimer SA, Dziura JD, Steil GM, Voskanyan GR, Steffen AT, Martin ML, Tamborlane WV. Effect of puberty on the pharmacodynamic and pharmacokinetic properties of insulin pump therapy in youth with type 1 diabetes. Diabetes Care. 2008 Jan;31(1):44-6. doi: 10.2337/dc07-0737. Epub 2007 Oct 1. No abstract available.
Results Reference
result
Learn more about this trial
Evaluation of Pharmacokinetics and Pharmacodynamic Properties of Rapid-Acting Insulin Analogs
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