Reliability of Insulin by Jet Injection

NCT02272296 | Completed Phase 4 DMC

• 1 other identifier: PKPD_INSJ_4
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Using a specific jet injector for the administration of a rapid-acting insulin analogue has been shown to advance the absorption of insulin from the subcutaneous area into the bloodstream by 40-50%, when compared to conventional injection by insulin pens. The reproducibility of the jet stream method has not been previously determined in vivo. It is also unknown how the efficacy of injecting regular insulin by jet stream compares to that of rapid-acting analogues injected by conventional pen. Objectives: 1. To compare the pharmacologic reproducibility of the rapid-acting insulin analogue aspart (Novorapid®) injected by jet-injection to that of the same insulin injected with a conventional pen. 2. To compare pharmacokinetic and -dynamic profile of regular insulin injected by jet injection to that of aspart insulin injected by conventional pen. Study design: Double-blind double-dummy randomized controlled parallel/cross-over

Conditions

Diabetes Mellitus

Keywords

Injections, Jet; pharmacology; Insulin Aspart; Equipment and Supplies

Outcome Measures

Primary Outcomes (2)

• (TmaxGIR)

  The variability in time until maximal glucose lowering effect, as determined by exogenous glucose requirement (TmaxGIR) to maintain normoglycemia, after insulin injection. Primary endpoint of main study

  0-6 hrs

• Tmax (min)

  Time to maximal exogenous glucose infusion rate (GIR, in ml/min/kg) required to maintain euglycaemia. Primary endpoint of sub study.

  0-6 hrs

Secondary Outcomes (7)

• CmaxGIR (mg/min)

  0-6 hrs

• CmaxINS (pmol/l)

  0-6 hrs

• TmaxINS (min)

  0-6 hrs

• AUCINS (pmol/min/l)

  0-6 hrs

• AUCGIR (g):

  0-6 hrs

Other Outcomes (1)

• Tolerability

  at second test day, at timepoint 0, for 5 minutes,

Study Arms (3)

Jet Injector_main study

ACTIVE COMPARATOR

Administration of insulin or placebo injection in main study

Device: jet injector; Device: Conventional pen (NovoPen IV)

conventional pen, NovoPen IV

PLACEBO COMPARATOR

Administration of insulin or placebo injection in main study

Device: jet injector; Device: Conventional pen (NovoPen IV)

jet injector_sub study

ACTIVE COMPARATOR

Administration of insulin or placebo injection in sub study

Device: jet injector

Interventions

jet injector DEVICE

1 administration of insulin in a dose of 0.2 units per kg body weight subcutaneously in the abdomen, 1 empty administration

Also known as: Insujet™, European Pharma Group, The Netherlands

Jet Injector_main study; conventional pen, NovoPen IV; jet injector_sub study

Conventional pen (NovoPen IV) DEVICE

1 administration of insulin in a dose of 0.2 units per kg body weight subcutaneously in the abdomen, 1 empty administration

Also known as: NovoPen IV, Novo Nordisk

Jet Injector_main study; conventional pen, NovoPen IV

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-50 years
• Body-Mass Index 18-32 kg/m2
• Blood pressure \<160/90 mmHg

You may not qualify if:

• Inability to provide informed consent
• Chronic use of medication other than oral contraceptives or thyroid hormone replacement therapy (with stable euthyroidism for at least 3 months)
• Treatment with systemic corticosteroids, immunosuppressive or cytostatic drugs
• Known allergy to aspart insulin
• 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 previous 6 months
• Presence of any other medical condition that might interfere with the study protocol
• Pregnancy or the intention to become pregnant
• Anemia, defined as an Hb of \<8.1 mmol/l for male subjects and \<7.5 for female subjects

Sponsors & Collaborators

• Radboud University Medical Center: lead

Study Sites (1)

Radboud university medical center

Nijmegen, 6542 JK, Netherlands

Location

Related Publications (12)

• 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.

  PMID: 16816837 BACKGROUND

• Malone JI, Lowitt S, Grove NP, Shah SC. Comparison of insulin levels after injection by jet stream and disposable insulin syringe. Diabetes Care. 1986 Nov-Dec;9(6):637-40. doi: 10.2337/diacare.9.6.637.

  PMID: 3542456 BACKGROUND

• Weller C, Linder M. Jet injection of insulin vs the syringe-and-needle method. JAMA. 1966 Mar 7;195(10):844-7. doi: 10.1001/jama.1966.03100100096027.

  PMID: 12608170 BACKGROUND

• Taylor R, Home PD, Alberti KG. Plasma free insulin profiles after administration of insulin by jet and conventional syringe injection. Diabetes Care. 1981 May-Jun;4(3):377-9. doi: 10.2337/diacare.4.3.377.

  PMID: 7047114 BACKGROUND

• Pehling GB, Gerich JE. Comparison of plasma insulin profiles after subcutaneous administration of insulin by jet spray and conventional needle injection in patients with insulin-dependent diabetes mellitus. Mayo Clin Proc. 1984 Nov;59(11):751-4. doi: 10.1016/s0025-6196(12)65585-2.

  PMID: 6387316 BACKGROUND

• Halle JP, Lambert J, Lindmayer I, Menassa K, Coutu F, Moghrabi A, Legendre L, Legault C, Lalumiere G. Twice-daily mixed regular and NPH insulin injections with new jet injector versus conventional syringes: pharmacokinetics of insulin absorption. Diabetes Care. 1986 May-Jun;9(3):279-82. doi: 10.2337/diacare.9.3.279.

  PMID: 3525057 BACKGROUND

• Kerum G, Profozic V, Granic M, Skrabalo Z. Blood glucose and free insulin levels after the administration of insulin by conventional syringe or jet injector in insulin treated type 2 diabetics. Horm Metab Res. 1987 Sep;19(9):422-5. doi: 10.1055/s-2007-1011842.

  PMID: 3319860 BACKGROUND

• Lucas A, Ribas L, Salinas I, Audi L, Sanmarti A, Foz M. Insulin levels after injection by jet stream and disposable syringe. Diabetes Care. 1988 Mar;11(3):298-9. doi: 10.2337/diacare.11.3.298a. No abstract available.

  PMID: 3046856 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.

  PMID: 21715522 BACKGROUND

• Gill GV, Yudkin JS, Keen H, Beran D. The insulin dilemma in resource-limited countries. A way forward? Diabetologia. 2011 Jan;54(1):19-24. doi: 10.1007/s00125-010-1897-3. Epub 2010 Sep 12.

  PMID: 20835860 BACKGROUND

• Julious SA. Sample sizes for clinical trials with normal data. Stat Med. 2004 Jun 30;23(12):1921-86. doi: 10.1002/sim.1783.

  PMID: 15195324 BACKGROUND

• Engwerda EEC, Tack CJ, de Galan BE. Pharmacokinetic and Pharmacodynamic Variability of Insulin When Administered by Jet Injection. J Diabetes Sci Technol. 2017 Sep;11(5):947-952. doi: 10.1177/1932296817699638. Epub 2017 Mar 17.

  PMID: 28303726 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Bastiaan E de Galan, MD, PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2014
• First Posted: October 22, 2014
• Study Start: February 1, 2015
• Primary Completion: August 1, 2015
• Study Completion: August 1, 2015
• Last Updated: October 28, 2015

Record last verified: 2015-10

Locations

NL (1)