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A Pooled Analysis of Clinical Pharmacology Trials Investigating the Pharmacokinetic and Pharmacodynamic Characteristics of Fast-Acting Insulin Aspart in Adults with Type 1 Diabetes.
Clin Pharmacokinet 2017; 56(5):551-559CP

Abstract

BACKGROUND

Fast-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation aiming to mimic the fast endogenous prandial insulin release more closely than currently available insulin products. In a post hoc analysis of pooled data from six clinical pharmacology trials, the pharmacological characteristics of faster aspart and IAsp were compared.

METHODS

The analysis included 218 adult subjects with type 1 diabetes from six randomised, double-blind, crossover trials in the faster aspart clinical development programme. Subjects received subcutaneous dosing (0.2 U/kg) of faster aspart and IAsp. In three trials, a 12-h euglycaemic clamp was performed (target 5.5 mmol/L; 100 mg/dL) to assess pharmacodynamics.

RESULTS

The pharmacokinetic and pharmacodynamic profiles were left-shifted for faster aspart versus IAsp. Onset of appearance occurred 4.9 min earlier (95% confidence interval [CI] faster aspart-IAsp: [-5.3 to -4.4], p < 0.001), early exposure (AUCIAsp,0-30min) was two times greater (estimated ratio faster aspart/IAsp 2.01 [1.87-2.17], p < 0.001) and offset of exposure (t Late 50% Cmax) occurred 12.2 min earlier [-17.9 to -6.5] (p < 0.001) for faster aspart versus IAsp. Accordingly, onset of action occurred 4.9 min earlier [-6.9 to -3.0] (p < 0.001), early glucose-lowering effect (AUCGIR,0-30min) was 74% greater (1.74 [1.47-2.10], p < 0.001) and offset of glucose-lowering effect (t Late 50% GIRmax) occurred 14.3 min earlier [-22.1 to -6.5] (p < 0.001) for faster aspart versus IAsp. Total exposure and total glucose-lowering effect did not differ significantly between treatments.

CONCLUSIONS

Faster aspart has the potential to better mimic the physiologic prandial insulin secretion and thereby to improve postprandial glucose control compared with IAsp. ClinicalTrials.gov identifiers: NCT02035371, NCT01924637, NCT02131246, NCT02033239, NCT02003677, NCT01618188.

Authors+Show Affiliations

Profil Institut für Stoffwechselforschung GmbH, Hellersbergstrasse 9, 41460, Neuss, Germany. tim.heise@profil.com.Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.Children's and Youth Hospital AUF DER BULT, Janusz-Korczak-Allee 12, 30173, Hannover, Germany.Novo Nordisk A/S, Vandtårnsvej 114, 2860, Søborg, Denmark.Novo Nordisk A/S, Vandtårnsvej 114, 2860, Søborg, Denmark.

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28205039

Citation

Heise, Tim, et al. "A Pooled Analysis of Clinical Pharmacology Trials Investigating the Pharmacokinetic and Pharmacodynamic Characteristics of Fast-Acting Insulin Aspart in Adults With Type 1 Diabetes." Clinical Pharmacokinetics, vol. 56, no. 5, 2017, pp. 551-559.
Heise T, Pieber TR, Danne T, et al. A Pooled Analysis of Clinical Pharmacology Trials Investigating the Pharmacokinetic and Pharmacodynamic Characteristics of Fast-Acting Insulin Aspart in Adults with Type 1 Diabetes. Clin Pharmacokinet. 2017;56(5):551-559.
Heise, T., Pieber, T. R., Danne, T., Erichsen, L., & Haahr, H. (2017). A Pooled Analysis of Clinical Pharmacology Trials Investigating the Pharmacokinetic and Pharmacodynamic Characteristics of Fast-Acting Insulin Aspart in Adults with Type 1 Diabetes. Clinical Pharmacokinetics, 56(5), pp. 551-559. doi:10.1007/s40262-017-0514-8.
Heise T, et al. A Pooled Analysis of Clinical Pharmacology Trials Investigating the Pharmacokinetic and Pharmacodynamic Characteristics of Fast-Acting Insulin Aspart in Adults With Type 1 Diabetes. Clin Pharmacokinet. 2017;56(5):551-559. PubMed PMID: 28205039.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Pooled Analysis of Clinical Pharmacology Trials Investigating the Pharmacokinetic and Pharmacodynamic Characteristics of Fast-Acting Insulin Aspart in Adults with Type 1 Diabetes. AU - Heise,Tim, AU - Pieber,Thomas R, AU - Danne,Thomas, AU - Erichsen,Lars, AU - Haahr,Hanne, PY - 2017/2/17/pubmed PY - 2017/11/29/medline PY - 2017/2/17/entrez SP - 551 EP - 559 JF - Clinical pharmacokinetics JO - Clin Pharmacokinet VL - 56 IS - 5 N2 - BACKGROUND: Fast-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation aiming to mimic the fast endogenous prandial insulin release more closely than currently available insulin products. In a post hoc analysis of pooled data from six clinical pharmacology trials, the pharmacological characteristics of faster aspart and IAsp were compared. METHODS: The analysis included 218 adult subjects with type 1 diabetes from six randomised, double-blind, crossover trials in the faster aspart clinical development programme. Subjects received subcutaneous dosing (0.2 U/kg) of faster aspart and IAsp. In three trials, a 12-h euglycaemic clamp was performed (target 5.5 mmol/L; 100 mg/dL) to assess pharmacodynamics. RESULTS: The pharmacokinetic and pharmacodynamic profiles were left-shifted for faster aspart versus IAsp. Onset of appearance occurred 4.9 min earlier (95% confidence interval [CI] faster aspart-IAsp: [-5.3 to -4.4], p < 0.001), early exposure (AUCIAsp,0-30min) was two times greater (estimated ratio faster aspart/IAsp 2.01 [1.87-2.17], p < 0.001) and offset of exposure (t Late 50% Cmax) occurred 12.2 min earlier [-17.9 to -6.5] (p < 0.001) for faster aspart versus IAsp. Accordingly, onset of action occurred 4.9 min earlier [-6.9 to -3.0] (p < 0.001), early glucose-lowering effect (AUCGIR,0-30min) was 74% greater (1.74 [1.47-2.10], p < 0.001) and offset of glucose-lowering effect (t Late 50% GIRmax) occurred 14.3 min earlier [-22.1 to -6.5] (p < 0.001) for faster aspart versus IAsp. Total exposure and total glucose-lowering effect did not differ significantly between treatments. CONCLUSIONS: Faster aspart has the potential to better mimic the physiologic prandial insulin secretion and thereby to improve postprandial glucose control compared with IAsp. ClinicalTrials.gov identifiers: NCT02035371, NCT01924637, NCT02131246, NCT02033239, NCT02003677, NCT01618188. SN - 1179-1926 UR - https://www.unboundmedicine.com/medline/citation/28205039/A_Pooled_Analysis_of_Clinical_Pharmacology_Trials_Investigating_the_Pharmacokinetic_and_Pharmacodynamic_Characteristics_of_Fast_Acting_Insulin_Aspart_in_Adults_with_Type_1_Diabetes_ L2 - https://dx.doi.org/10.1007/s40262-017-0514-8 DB - PRIME DP - Unbound Medicine ER -