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Pharmacokinetics/Dynamics of Basal (Continuous) Insulin Infusion Administered Either Intradermally or Subcutaneously

Primary Purpose

Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Intradermal insulin delivery: BD Research Catheter Set
Subcutaneous insulin delivery:ACCU-CHEK Rapid-D Infusion Set
Sponsored by
Becton, Dickinson and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Diabetes Mellitus, Type 1 focused on measuring Diabetes, Insulin Therapy, Blood Glucose, Basal insulin, Diabetics

Eligibility Criteria

18 Years - 55 Years (Adult)MaleDoes not accept healthy volunteers

20 Male Type 1 Diabetic Mellitus subjects on Continuous Subcutaneous Insulin Infusion (CSII) therapy.

Inclusion Criteria:

  • Understood and signed informed consent obtained before any trial-related activities (trial-related activities are any procedures that would not have been performed during normal management of the subject)
  • Type 1 Diabetes mellitus, according to clinical judgment / ADA / WHO-definition (Diabetes Care 2003; 26: 5-20) for at least 1 year
  • Current treatment:Insulin Pump
  • Age in the range of greater than or equal to 18 and less than or equal to 55 years
  • Body mass index (BMI) less than or equal to 32 kg/m²
  • HbA1c less than or equal to 9.0 %
  • Able and willing to adhere to the study procedures for the entire trial period
  • Negative test results for hepatitis C antibodies, hepatitis B surface antigen and HIV at screening.

Exclusion Criteria:

  • Previous participation in this trial or participation in a clinical trial within 3 months prior screening examination
  • Any symptoms suggestive of, or a diagnosis or treatment for gastroparesis
  • Abnormalities in renal function (e.g. serum creatinine >1.2 mg/dl) or judged by the investigator that would pose a problem of clearance of injected insulin
  • Proliferative retinopathy or maculopathy that has required acute treatment within the last six months
  • Acute and severe illness apart from diabetes mellitus as judged by the investigator
  • Abnormalities in the laboratory parameters if judged as clinically significant by the investigator. In particular, subjects with GOT/GPT >3x, thrombocyte count <100/nL, INR >1.3, PTT >50 sec. will not be permitted to enter the study.
  • Clinically significant abnormalities in the ECG
  • Recurrent major hypoglycemia or hypoglycemic unawareness as judged by the investigator
  • Lipodystrophy which in the judgment of the investigator would pose a problem in terms of variability of absorption of injected insulin
  • Use of systemic corticoids for the last three months prior to screening examination or treatment with medication known to interfere with glucose metabolism such as non-selective ß-blockers, or mono amine oxidase (MAO) inhibitors, ACE-inhibitors or thiazides, unless medical treatment having existed for at least three month prior screening examination
  • Any disease requiring use of anti-coagulants
  • Impaired hepatic or renal functions as judged by the investigator
  • Cardiac problems as judged by the investigator
  • Uncontrolled hypertension (treated or untreated) as judged by the investigator (RRsyst. >140 mmHg, RRdiast. > 90 mmHg)
  • Mental incapacity, unwillingness or language barriers precluding adequate understanding or co-operation
  • Current addiction to alcohol or substances of abuse as determined by the investigator
  • Allergy to plaster/adhesive
  • Any other condition that the investigator feels would interfere with trial participation or evaluation of results.
  • Donation of any blood or plasma in the past month or in excess of 500 mL within the 12 weeks preceding screening
  • Subjects with a history of deep leg vein thrombosis or with frequent appearance of deep leg vein thrombosis in 1st degree relatives as judged by the investigator

Sites / Locations

  • Profil Institut für Stoffwechselforschung GmbH

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Intradermal insulin infusion (ID)

Subcutaneous insulin infusion (SC)

Arm Description

Outcomes

Primary Outcome Measures

Insulin measurements will be used to compute PK model parameters: absorption rate(s) and elimination rate using an appropriate transport model.

Secondary Outcome Measures

Pharmacodynamic glycemic parameters will be as follows: time from insulin infusion onset to glycemic nadir; time from test insulin shutoff to return to baseline glucose; amount of additional drop in blood glucose following test insulin infusion shutoff
Evidence of safety and tolerability of intradermally infused insulin
Feasibility of RCS for longer-term ID infusion

Full Information

First Posted
January 29, 2010
Last Updated
March 9, 2010
Sponsor
Becton, Dickinson and Company
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1. Study Identification

Unique Protocol Identification Number
NCT01061216
Brief Title
Pharmacokinetics/Dynamics of Basal (Continuous) Insulin Infusion Administered Either Intradermally or Subcutaneously
Official Title
A Mono-center, Open Label, Randomised 2-period Crossover Study to Compare the Pharmacokinetics and Pharmacodynamics of Continuous Insulin Infusion Administered Either Intradermally or Subcutaneously in Subjects With Type 1 Diabetes Mellitus
Study Type
Interventional

2. Study Status

Record Verification Date
March 2010
Overall Recruitment Status
Completed
Study Start Date
January 2010 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
March 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Becton, Dickinson and Company

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The primary objective of this study will be to assess the PK/PD responsiveness of basal ID administered insulin compared to SC, and to determine the safety and local tolerability of extended (two six-hour periods) microneedle insulin delivery (MID) infusion. The primary endpoint will be the PK response to changes in rapid-acting insulin basal infusion rate. Faster PK transitions coupled with faster PD responsiveness could provide clinical benefit, compared to current subcutaneous insulin infusion. In addition, for nocturnal basal pumping, more rapid insulin offset could decrease the occurrence rate and severity of hypoglycemic episodes.
Detailed Description
Twenty (20) male T1 diabetic subjects will be studied under manual partial glucose clamp conditions over a 16 hour infusion period (approximately 36 hours of overall time in clinic). Subjects will be admitted to the clinic the night before their study visit for overnight stabilization in which, via insulin and/or glucose infusions, blood glucose will be stabilized to approximately 140 mg/dL. Subjects will receive as background IV Humulin insulin with an initial dose equivalent to one-half of their usual daily basal insulin dose. In the morning the subjects will start the experimental intervention and have administered a low rate stair-stepped Lispro insulin infusion profile via an infusion pump (Harvard Syringe Pump, Harvard Apparatus). The profile is designed to examine the initial "on" rate for microneedle insulin delivery, the transition time between basal rate changes and the "off-rate" after insulin cessation. Subjects will receive the same profile by SC infusion on a second clinic day in a randomized order. PK endpoints will be established using timed blood samples. Safety and tolerability at the local infusion site will also be recorded. In parallel, using a commercially available insulin pump (One Touch "Ping" Insulin Pump, Animas) and an infusion set (either the RCS or a commercially available SC insulin infusion set); a second infusion of insulin diluent will be used to assess the feasibility of longer-term ID infusions (16 hours) as compared to SC. During each infusion the pumps will control the fluid delivery rate and volume. In addition an in-line pressure transducer will record the pressure and transfer the information to a laptop computer. Primary Objective: To define the PK profile of initiation, rate change, and discontinuation of continuously infused basal insulin administered either intradermally or subcutaneously over two separate infusion periods. Secondary Objectives: Determine the PD effect of the infused insulin as measured by time to glucose rebound following discontinuation of test insulin infusion. Assess the safety and tolerability of intradermally infused insulin over two six-hour periods. Assess the feasibility of the research catheter set (RCS) for longer-term ID infusion

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2
Keywords
Diabetes, Insulin Therapy, Blood Glucose, Basal insulin, Diabetics

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intradermal insulin infusion (ID)
Arm Type
Experimental
Arm Title
Subcutaneous insulin infusion (SC)
Arm Type
Active Comparator
Intervention Type
Device
Intervention Name(s)
Intradermal insulin delivery: BD Research Catheter Set
Intervention Description
1 unit/hr rapid acting insulin delivered intradermally for 6 hours 4 hour washout period (no insulin delivered) 2 units/hr rapid acting insulin delivered intradermally for 6 hours 4 hour washout period (no insulin delivered)
Intervention Type
Device
Intervention Name(s)
Subcutaneous insulin delivery:ACCU-CHEK Rapid-D Infusion Set
Other Intervention Name(s)
ACCU-CHEK, Rapid-D Infusion Set (Disetronic, USA)
Intervention Description
1 unit per hour of rapid acting insulin infusion for 6 hours 4 hour washout (no insulin delivered) 2 unit per hour of rapid acting insulin infusion for 6 hours 4 hour washout (no insulin delivered)
Primary Outcome Measure Information:
Title
Insulin measurements will be used to compute PK model parameters: absorption rate(s) and elimination rate using an appropriate transport model.
Time Frame
20 hours
Secondary Outcome Measure Information:
Title
Pharmacodynamic glycemic parameters will be as follows: time from insulin infusion onset to glycemic nadir; time from test insulin shutoff to return to baseline glucose; amount of additional drop in blood glucose following test insulin infusion shutoff
Time Frame
20 hours
Title
Evidence of safety and tolerability of intradermally infused insulin
Time Frame
26 hours
Title
Feasibility of RCS for longer-term ID infusion
Time Frame
16 hours

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
20 Male Type 1 Diabetic Mellitus subjects on Continuous Subcutaneous Insulin Infusion (CSII) therapy. Inclusion Criteria: Understood and signed informed consent obtained before any trial-related activities (trial-related activities are any procedures that would not have been performed during normal management of the subject) Type 1 Diabetes mellitus, according to clinical judgment / ADA / WHO-definition (Diabetes Care 2003; 26: 5-20) for at least 1 year Current treatment:Insulin Pump Age in the range of greater than or equal to 18 and less than or equal to 55 years Body mass index (BMI) less than or equal to 32 kg/m² HbA1c less than or equal to 9.0 % Able and willing to adhere to the study procedures for the entire trial period Negative test results for hepatitis C antibodies, hepatitis B surface antigen and HIV at screening. Exclusion Criteria: Previous participation in this trial or participation in a clinical trial within 3 months prior screening examination Any symptoms suggestive of, or a diagnosis or treatment for gastroparesis Abnormalities in renal function (e.g. serum creatinine >1.2 mg/dl) or judged by the investigator that would pose a problem of clearance of injected insulin Proliferative retinopathy or maculopathy that has required acute treatment within the last six months Acute and severe illness apart from diabetes mellitus as judged by the investigator Abnormalities in the laboratory parameters if judged as clinically significant by the investigator. In particular, subjects with GOT/GPT >3x, thrombocyte count <100/nL, INR >1.3, PTT >50 sec. will not be permitted to enter the study. Clinically significant abnormalities in the ECG Recurrent major hypoglycemia or hypoglycemic unawareness as judged by the investigator Lipodystrophy which in the judgment of the investigator would pose a problem in terms of variability of absorption of injected insulin Use of systemic corticoids for the last three months prior to screening examination or treatment with medication known to interfere with glucose metabolism such as non-selective ß-blockers, or mono amine oxidase (MAO) inhibitors, ACE-inhibitors or thiazides, unless medical treatment having existed for at least three month prior screening examination Any disease requiring use of anti-coagulants Impaired hepatic or renal functions as judged by the investigator Cardiac problems as judged by the investigator Uncontrolled hypertension (treated or untreated) as judged by the investigator (RRsyst. >140 mmHg, RRdiast. > 90 mmHg) Mental incapacity, unwillingness or language barriers precluding adequate understanding or co-operation Current addiction to alcohol or substances of abuse as determined by the investigator Allergy to plaster/adhesive Any other condition that the investigator feels would interfere with trial participation or evaluation of results. Donation of any blood or plasma in the past month or in excess of 500 mL within the 12 weeks preceding screening Subjects with a history of deep leg vein thrombosis or with frequent appearance of deep leg vein thrombosis in 1st degree relatives as judged by the investigator
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Christoph Kapitza, Dr. med.
Organizational Affiliation
Profil Institut für Stoffwechselforschung GmbH
Official's Role
Principal Investigator
Facility Information:
Facility Name
Profil Institut für Stoffwechselforschung GmbH
City
Neuss
ZIP/Postal Code
D-41460
Country
Germany

12. IPD Sharing Statement

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Pharmacokinetics/Dynamics of Basal (Continuous) Insulin Infusion Administered Either Intradermally or Subcutaneously

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