Clinical trial NCT01438632: Pharmacology of Insulin Injected With Jet-injection in Diabetes
Official title: Pharmacology of Rapid-acting Insulin Injected by Needle-free Jet-injection in Patients With Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus
Keywords: Insulin action
Jet injector
Diabetes Mellitus
Pharmacodynamics
Pharmacokinetics
Insulin analogs
Insulin aspart
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
Collaborators: name: European Pharma Group (EPG)
First posted: 2011-09-22
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: 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.
timeFrame: 2 days (2 hours per day)
Secondary outcomes:
measure: BGmax (mmol/l): maximal glucose excursion after insulin injection and meal ingestion
timeFrame: 2 days (6 hours each day)
measure: T-BGmax (min): time to maximal glucose excursion after insulin injection and meal ingestion
timeFrame: 2 days (6 hours per day)
measure: 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
timeFrame: 2 days (6 hours each day)
measure: T-BGBL (min): time until plasma glucose has returned to baseline values after insulin injection and meal ingestion
timeFrame: 2 days (6 hours per day)
measure: T-INSmax (min): time to maximal insulin concentration (C-INSmax)
timeFrame: 2 days (6 hours per day)
measure: INSAUC (pmol•min-1•l-1): area under the insulin concentration curve (from timepoint 0)
timeFrame: 2 days (6 hours per day)
measure: T-INSAUC50% (min): time until 50% of insulin absorption (mean residence time, MRT)
timeFrame: 2 days (6 hours each day)
measure: Number of patients requiring exogenous glucose infusion to prevent postprandial hypoglycaemia after insulin injection and meal ingestion
timeFrame: 2 days
measure: Amount of exogenous glucose required to prevent postprandial hypoglycaemia after insulin injection and meal ingestion
timeFrame: 2 days
measure: Duration of time that exogenous glucose is required to prevent postprandial hypoglycaemia after insulin injection and meal ingestion
timeFrame: 2 days
measure: BG-AUC0-1h
timeFrame: 2 days (6 hours per day)
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Department of general internal medicine 463, section Diabetes, Radboud University Nijmegen Medical Centre
state: Gelderland
Study officials:
affiliation: Radboud University Nijmegen Medical Centre, Department of general internal medicine 463, section Diabetes
name: Bastiaan E de Galan, MD, PhD
role: STUDY_DIRECTOR
affiliation: Department of general internal medicine 463, section Diabetes, Radboud University Nijmegen Medical Centre
name: Elsemiek EC Engwerda, BSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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. doi: 10.2337/dc06-0383.
citation: 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.