Pharmacology of Insulin Injected With Jet-injection in Diabetes

NCT ID: NCT01438632

Last Updated: 2013-03-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-09-30
• Study Completion Date: 2012-07-31

Brief Summary

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.

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.

Conditions

Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: EXPERIMENTAL

jet injection device

Intervention Type: 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.

conventional insulin pen

Group Type: ACTIVE_COMPARATOR

jet injection device

Intervention Type: 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.

Interventions

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.

Intervention Type: DEVICE

Other Intervention Names

Jet injector: InsuJet™ from the European Pharma Group; Insulin device: NovoPen® 3 from Novo Nordisk

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Pharma Group (EPG)

UNKNOWN

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bastiaan E de Galan, MD, PhD

Role: STUDY_DIRECTOR

Radboud University Nijmegen Medical Centre, Department of general internal medicine 463, section Diabetes

Elsemiek EC Engwerda, BSc

Role: PRINCIPAL_INVESTIGATOR

Department of general internal medicine 463, section Diabetes, Radboud University Nijmegen Medical Centre

Locations

Department of general internal medicine 463, section Diabetes, Radboud University Nijmegen Medical Centre

Nijmegen, Gelderland, Netherlands

Countries

Netherlands

References

Mitragotri S. Current status and future prospects of needle-free liquid jet injectors. Nat Rev Drug Discov. 2006 Jul;5(7):543-8. doi: 10.1038/nrd2076.

Reference Type: BACKGROUND

PMID: 16816837 (View on PubMed)

Rave K, Klein O, Frick AD, Becker RH. Advantage of premeal-injected insulin glulisine compared with regular human insulin in subjects with type 1 diabetes. Diabetes Care. 2006 Aug;29(8):1812-7. doi: 10.2337/dc06-0383.

Reference Type: BACKGROUND

PMID: 16873785 (View on PubMed)

Engwerda EE, Abbink EJ, Tack CJ, de Galan BE. Improved pharmacokinetic and pharmacodynamic profile of rapid-acting insulin using needle-free jet injection technology. Diabetes Care. 2011 Aug;34(8):1804-8. doi: 10.2337/dc11-0182. Epub 2011 Jun 29.

Reference Type: BACKGROUND

PMID: 21715522 (View on PubMed)

Other Identifiers

PKPD_INSJ_2

Identifier Type: -

Identifier Source: org_study_id