Evaluation of Pharmacokinetics and Pharmacodynamic Properties of Rapid-Acting Insulin Analogs (PK/PD)

August 30, 2016 updated by: Yale University

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)

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

8 years to 17 years (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Age 8-17 (inclusive), of whom 15 will be prepubertal and 60 pubertal;
  2. Clinical diagnosis of T1D (based on clinical presentation, insulin dependence,and/or history of ketosis;
  3. Diagnosis of T1D for at least one year's duration;
  4. On CSII therapy for at least three months;
  5. HbA1c 6.5-8.0%, inclusive;
  6. Body mass index < 95% for age and gender;
  7. Meeting minimum weight requirement of at least 17.6 kg (for pre-pubertal subjects) or 34.6 kg (for pubertal subjects)
  8. Ability to comprehend written and spoken English

Exclusion Criteria:

  1. Any other medical disease aside from T1D or treated hypothyroidism
  2. Receiving any other medication besides insulin or levothyroxine
  3. Female subjects of reproductive potential who may be pregnant, breast feeding, or not consistently utilizing barrier methods or abstinence as contraception
  4. Inability to comprehend written and spoken English
  5. 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
ACTIVE_COMPARATOR: Catheter day 4
Adolescents with type 1 diabetes with catheters day #4
Drug: Insulin analogs (Lispro and Aspart)
Insulin bolus given through insulin pump
Other Names:
  • Humalog, Novolog
ACTIVE_COMPARATOR: Catheter day 1
Adolescents with type 1 diabetes with catheter day #1
Drug: Insulin analogs (Lispro and Aspart)
Insulin bolus given through insulin pump
Other Names:
  • Humalog, Novolog
ACTIVE_COMPARATOR: Aspart and Detemir
Adolescents with type 1 diabetes
Drug: Insulin analogs (Aspart and Detemir)
Drugs given separately
Drug: Insulin analogs (Aspart and Detemir)
Drugs given in the same injection
ACTIVE_COMPARATOR: Lispro and Glargine
Adolescents with type 1 diabetes
Drug: Insulin analogs (Lispro and Glargine)
Drugs given separately
Drug: Insulin analogs (Lispro and Glargine)
Drugs given in single injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Maximum Glucose Infusion Rate (GIR) to maintain euglycemia
Time Frame: Six hour observation period
Six hour observation period

Secondary Outcome Measures

Outcome Measure
Time Frame
Time to Maximum Glucose Infusion Rate
Time Frame: Six Hour Observation period
Six Hour Observation period

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yale University

Investigators

  • Principal Investigator: Stuart A Weinzimer, MD, Yale University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2007

Primary Completion (ACTUAL)

September 1, 2011

Study Completion (ACTUAL)

September 1, 2011

Study Registration Dates

First Submitted

March 27, 2008

First Submitted That Met QC Criteria

March 31, 2008

First Posted (ESTIMATE)

April 3, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

September 1, 2016

Last Update Submitted That Met QC Criteria

August 30, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 403026582
  • JDRF Hypoglycemia Grant

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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