title: Intradermal insulin infusion achieves faster insulin action than subcutaneous infusion for 3-day wear.
abstract: Rapid uptake previously demonstrated by intradermal (ID) drug administration indicates compound delivery within the dermis may have clinical and pharmacological advantages for certain drug therapies. This study is the first clinical trial to evaluate continuous microneedle-based drug infusion, device wearability, and intradermal microneedle insulin kinetics over a multi-day (72 h) wear period. This was a single center, open-label, two-period crossover study in T1DM patients on continuous subcutaneous insulin infusion (CSII). Patients received treatment during interventional visits: one SC and one ID basal/bolus infusion of insulin aspart (NovoRapid® U-100) administered over 3 days in a randomized order. Twenty-eight patients were randomized and exposed to trial product, and 23 completed the study. Bolus insulin infusions were given prior to standardized breakfast and lunch test meals on each of the three treatment days. Blood samples were drawn at predefined time points for measurements of insulin aspart and blood glucose in serum. The primary endpoint insulin Tmax demonstrated that ID bolus infusion was associated with a significantly shorter Tmax with statistically significantly smaller intra-subject variability, compared to SC infusion, and this difference was maintained over three treatment days. Analyses of secondary PK endpoints corresponded with the primary endpoint findings. Postprandial glycemic response was significantly less pronounced after ID bolus: For most endpoints ID vs. SC, differences were statistically significant within the 0-1.5 or 0-2 h time period. Intradermal delivery of insulin is a viable delivery route alternative providing reduced time for insulin absorption with less intra-subject variability and lower glycemic response.
authors.affiliation: BD Technologies, Durham, NC, USA, christopher_rini@bd.com.
authors.forename: Christopher James
authors.initials: CJ
authors.lastname: Rini
authors.forename: Elaine
authors.initials: E
authors.lastname: McVey
authors.forename: Diane
authors.initials: D
authors.lastname: Sutter
authors.forename: Stephen
authors.initials: S
authors.lastname: Keith
authors.forename: Heinz-Joerg
authors.initials: HJ
authors.lastname: Kurth
authors.forename: Leszek
authors.initials: L
authors.lastname: Nosek
authors.forename: Christoph
authors.initials: C
authors.lastname: Kapitza
authors.forename: Kerstin
authors.initials: K
authors.lastname: Rebrin
authors.forename: Laurence
authors.initials: L
authors.lastname: Hirsch
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Pettis
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D016503:Drug Delivery Systems / Q000295:instrumentation*; D004867:Equipment Design; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D055104:Infusions, Subcutaneous / Q000295:instrumentation; D007271:Injections, Intradermal / Q000295:instrumentation; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D007332:Insulin Infusion Systems; D008297:Male; D008845:Microinjections / Q000295:instrumentation*; D009339:Needles; D019518:Postprandial Period; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin