Pharmacology of Insulin Injected With Jet-injection in Diabetes

This study has been completed.
Sponsor:
Collaborator:
European Pharma Group (EPG)
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT01438632
First received: September 19, 2011
Last updated: March 11, 2013
Last verified: August 2011
  Purpose

A previous study showed that absorption and glucose-lowering action of rapid-acting insulin analogues occurred twice as fast when these analogues were administered by jet injection technology rather than by conventional insulin pen in healthy non-diabetic subjects. This study investigates if the rapid-acting insulin analogue aspart (Novorapid®) injected with jet-injection or a conventional insulin pen prior to a standardised meal in patients with diabetes shows the same difference in the pharmacokinetic and pharmacodynamic profile.


Condition Intervention Phase
Diabetes Mellitus
Device: jet injection device
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Pharmacology of Rapid-acting Insulin Injected by Needle-free Jet-injection in Patients With Diabetes

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • BG-AUC0-2h (mmol•min-1•l-1): area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 2 h after insulin injection and meal ingestion. [ Time Frame: 2 days (2 hours per day) ] [ Designated as safety issue: No ]
    based on plasma glucose levels during the first two hours of the 6-hour post-meal study duration


Secondary Outcome Measures:
  • BGmax (mmol/l): maximal glucose excursion after insulin injection and meal ingestion [ Time Frame: 2 days (6 hours each day) ] [ Designated as safety issue: No ]
    Maximal plasma glucose value after the standardised meal

  • T-BGmax (min): time to maximal glucose excursion after insulin injection and meal ingestion [ Time Frame: 2 days (6 hours per day) ] [ Designated as safety issue: No ]
    Time until maximal glucose value after the standardised meal and insulin injection

  • BG-AUC0-6h (mmol•min-1•l-1): area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 6 h after insulin injection and meal ingestion [ Time Frame: 2 days (6 hours each day) ] [ Designated as safety issue: No ]
    Based on glucose concentration measurements for the total 6 hours of the study

  • T-BGBL (min): time until plasma glucose has returned to baseline values after insulin injection and meal ingestion [ Time Frame: 2 days (6 hours per day) ] [ Designated as safety issue: No ]
    based on glucose level measurements during the total 6 hours of the study

  • T-INSmax (min): time to maximal insulin concentration (C-INSmax) [ Time Frame: 2 days (6 hours per day) ] [ Designated as safety issue: No ]
    Maximal insulin concentration after insulin injection

  • INSAUC (pmol•min-1•l-1): area under the insulin concentration curve (from timepoint 0) [ Time Frame: 2 days (6 hours per day) ] [ Designated as safety issue: No ]
    Based on insulin concentration measurements during the total 6 hours of the study

  • T-INSAUC50% (min): time until 50% of insulin absorption (mean residence time, MRT) [ Time Frame: 2 days (6 hours each day) ] [ Designated as safety issue: No ]
    Based on insulin concentration measurements during the total 6 hours of the study

  • Number of patients requiring exogenous glucose infusion to prevent postprandial hypoglycaemia after insulin injection and meal ingestion [ Time Frame: 2 days ] [ Designated as safety issue: Yes ]
    This will be assessed for the individual patient after every test. After completion of the experiments all cases of hypoglycemia will be assessed

  • Amount of exogenous glucose required to prevent postprandial hypoglycaemia after insulin injection and meal ingestion [ Time Frame: 2 days ] [ Designated as safety issue: Yes ]
    This will be assessed for the individual patient after every test. After completion of the experiments the total amount of glucose infused will be calculate for each device

  • Duration of time that exogenous glucose is required to prevent postprandial hypoglycaemia after insulin injection and meal ingestion [ Time Frame: 2 days ] [ Designated as safety issue: Yes ]
    This will be assessed for the individual patient after every test. After completion of the experiments the total amount of time will be calculate for each device

  • BG-AUC0-1h [ Time Frame: 2 days (6 hours per day) ] [ Designated as safety issue: No ]
    the area under the baseline-subtracted plasma glucose concentration time-curve during the first hour


Enrollment: 24
Study Start Date: September 2011
Study Completion Date: July 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: jet injector
Jet injectors deliver insulin at a high velocity (typically >100m/s) across the skin in the subcutaneous tissue, without the use of a needle
Device: jet injection device
Rapid-acting insulin analogue aspart (Novorapid®) administration by means of a jet injector or a conventional insulin pen in the subcutaneous tissue. Dosage of insulin will be determined by the normal dosage of insulin used by the patient before breakfast.
Other Names:
  • Jet injector: InsuJet™ from the European Pharma Group
  • Insulin device: NovoPen® 3 from Novo Nordisk
Active Comparator: conventional insulin pen Device: jet injection device
Rapid-acting insulin analogue aspart (Novorapid®) administration by means of a jet injector or a conventional insulin pen in the subcutaneous tissue. Dosage of insulin will be determined by the normal dosage of insulin used by the patient before breakfast.
Other Names:
  • Jet injector: InsuJet™ from the European Pharma Group
  • Insulin device: NovoPen® 3 from Novo Nordisk

Detailed Description:

A previous study showed that absorption and glucose-lowering action of rapid-acting insulin analogues occurred twice as fast when these analogues were administered by jet injection technology rather than by conventional insulin pen in healthy non-diabetic subjects. This study investigates if the rapid-acting insulin analogue aspart (Novorapid®) injected with jet-injection or a conventional insulin pen prior to a standardised meal in patients with diabetes (type 1 and type 2) shows the same difference in the pharmacokinetic and pharmacodynamic profile.The pharmacokinetic and pharmacodynamic profile of insulin aspart will be derived from the time-action profiles of insulin and glucose, respectively, in response to insulin injected directly prior to a standardised meal. All patients will be investigated twice, where on one occasion the jet-injector device will be used to inject an individualised dose of insulin and a conventional insulin pen to inject a placebo solution, and on the other occasion insulin will be injected with the conventional pen and placebo with the jet-injector. The order of these occasions will be randomised and blinded to both the investigator and the participating patient. The primary endpoint is the hyperglycaemic burden as reflected by area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 2 h after insulin injection and meal ingestion (BG-AUC0-2h). Secondary study endpoints are the area under the baseline-subtracted plasma glucose concentration time-curve from time 0 to 6 h (BG-AUC0-6h), maximal glucose excursion (BGmax), time to maximal glucose excursion (T-BGmax), time until plasma glucose has returned to baseline (T-BGBL), maximal insulin concentration (C-INSmax), time to maximal insulin concentration (T-INSmax), area under the insulin concentration curve (INSAUC) and time until 50% of insulin absorption (T-INSAUC50%) after insulin injection and meal ingestion.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Body-mass index 18-32 kg/m2
  • Stable glycaemic control with HbA1c 6.0-9.0%
  • Duration of diabetes >1 year
  • Insulin use at least once daily or with subcutaneous pump
  • Blood pressure <160/90 mmHg

Exclusion Criteria:

  • Inability to provide informed consent
  • Requirement of <8 units of rapid-acting insulin (analogue) before meals
  • Chronic use of sulphonylurea derivatives, GLP-1 based treatments, acarbose or thiazolidinediones
  • Treatment with prednisolone, non-steroidal anti-inflammatory drugs (NSAIDs), immunosuppressive agents, cytostatic drugs, hormone therapy except insulin, thyroid supplementation and oral anticonceptives
  • Known allergy to aspart insulin
  • Symptomatic diabetic neuropathy
  • History of a major cardiovascular disease event (myocardial infarction, stroke, symptomatic peripheral artery disease, coronary bypass surgery, percutaneous coronary or peripheral artery angioplasty) in the past 6 months
  • Pregnancy or the intention to become pregnant
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01438632

Locations
Netherlands
Department of general internal medicine 463, section Diabetes, Radboud University Nijmegen Medical Centre
Nijmegen, Gelderland, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
European Pharma Group (EPG)
Investigators
Study Director: Bastiaan E de Galan, MD, PhD Radboud University Nijmegen Medical Centre, Department of general internal medicine 463, section Diabetes
Principal Investigator: Elsemiek EC Engwerda, BSc Department of general internal medicine 463, section Diabetes, Radboud University Nijmegen Medical Centre
  More Information

Publications:
Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01438632     History of Changes
Other Study ID Numbers: PKPD_INSJ_2
Study First Received: September 19, 2011
Last Updated: March 11, 2013
Health Authority: Netherlands: The Committee on Research Involving Human Subjects Arnhem Nijmegen (CMO)

Keywords provided by Radboud University:
Insulin action
Jet injector
Diabetes Mellitus
Pharmacodynamics
Pharmacokinetics
Insulin analogs
Insulin aspart

Additional relevant MeSH terms:
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Insulin
Insulin, Short-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 28, 2014