Pharmacology of Insulin Injected With Jet-injection in Diabetes

Diabetes Mellitus Clinical Trial

Official title:

Pharmacology of Rapid-acting Insulin Injected by Needle-free Jet-injection in Patients With Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01438632
• Other study ID #: PKPD_INSJ_2
• Status: Completed
• Phase: Phase 4
• First received: September 19, 2011
• Last updated: March 11, 2013
• Start date: September 2011
• Est. completion date: July 2012

Study information

• Verified date: August 2011
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Committee on Research Involving Human Subjects Arnhem Nijmegen (CMO)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: July 2012
• Est. primary completion date: May 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus

Intervention

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.

Locations

Country	Name	City	State
Netherlands	Department of general internal medicine 463, section Diabetes, Radboud University Nijmegen Medical Centre	Nijmegen	Gelderland

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University	European Pharma Group (EPG)

Country where clinical trial is conducted

Netherlands, 

References & Publications (3)

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. — View Citation

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

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	based on plasma glucose levels during the first two hours of the 6-hour post-meal study duration	2 days (2 hours per day)	No
Secondary	BGmax (mmol/l): maximal glucose excursion after insulin injection and meal ingestion	Maximal plasma glucose value after the standardised meal	2 days (6 hours each day)	No
Secondary	T-BGmax (min): time to maximal glucose excursion after insulin injection and meal ingestion	Time until maximal glucose value after the standardised meal and insulin injection	2 days (6 hours per day)	No
Secondary	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	Based on glucose concentration measurements for the total 6 hours of the study	2 days (6 hours each day)	No
Secondary	T-BGBL (min): time until plasma glucose has returned to baseline values after insulin injection and meal ingestion	based on glucose level measurements during the total 6 hours of the study	2 days (6 hours per day)	No
Secondary	T-INSmax (min): time to maximal insulin concentration (C-INSmax)	Maximal insulin concentration after insulin injection	2 days (6 hours per day)	No
Secondary	INSAUC (pmol•min-1•l-1): area under the insulin concentration curve (from timepoint 0)	Based on insulin concentration measurements during the total 6 hours of the study	2 days (6 hours per day)	No
Secondary	T-INSAUC50% (min): time until 50% of insulin absorption (mean residence time, MRT)	Based on insulin concentration measurements during the total 6 hours of the study	2 days (6 hours each day)	No
Secondary	Number of patients requiring exogenous glucose infusion to prevent postprandial hypoglycaemia after insulin injection and meal ingestion	This will be assessed for the individual patient after every test. After completion of the experiments all cases of hypoglycemia will be assessed	2 days	Yes
Secondary	Amount of exogenous glucose required to prevent postprandial hypoglycaemia after insulin injection and meal ingestion	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	2 days	Yes
Secondary	Duration of time that exogenous glucose is required to prevent postprandial hypoglycaemia after insulin injection and meal ingestion	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	2 days	Yes
Secondary	BG-AUC0-1h	the area under the baseline-subtracted plasma glucose concentration time-curve during the first hour	2 days (6 hours per day)	No