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| Name | Class |
|---|---|
| European Pharma Group (EPG) | UNKNOWN |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| jet injector | Experimental | Jet injectors deliver insulin at a high velocity (typically >100m/s) across the skin in the subcutaneous tissue, without the use of a needle |
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| conventional insulin pen | Active Comparator |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| jet injection device | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| T-BGmax (min): time to maximal glucose excursion after insulin injection and meal ingestion |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bastiaan E de Galan, MD, PhD | Radboud University Nijmegen Medical Centre, Department of general internal medicine 463, section Diabetes | Study Director |
| Elsemiek EC Engwerda, BSc | Department of general internal medicine 463, section Diabetes, Radboud University Nijmegen Medical Centre | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of general internal medicine 463, section Diabetes, Radboud University Nijmegen Medical Centre | Nijmegen | Gelderland | 6500 HB | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16816837 | Background | 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. | |
| 16873785 | Background | 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. |
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| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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Time until maximal glucose value after the standardised meal and insulin injection |
| 2 days (6 hours per day) |
| 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) |
| 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) |
| T-INSmax (min): time to maximal insulin concentration (C-INSmax) | Maximal insulin concentration after insulin injection | 2 days (6 hours per day) |
| 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) |
| 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) |
| 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 |
| 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 |
| 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 |
| BG-AUC0-1h | the area under the baseline-subtracted plasma glucose concentration time-curve during the first hour | 2 days (6 hours per day) |
| 21715522 | Background | 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. |