title: Pharmacokinetic and prandial pharmacodynamic properties of insulin degludec/insulin aspart in children, adolescents, and adults with type 1 diabetes.
abstract: Insulin degludec/insulin aspart (IDegAsp) is a soluble coformulation of long-acting insulin degludec and short-acting insulin aspart. This open-label, Phase 1 study aimed to determine the pharmacodynamic and pharmacokinetic properties of IDegAsp in children (6-11 yr), adolescents (12-17 yr), and adults (18-65 yr) with type 1 diabetes mellitus (T1DM). Thirty-eight subjects received single subcutaneous IDegAsp dosing (0.5 U/kg) immediately before a standardized liquid meal (17.3 g carbohydrates/100 mL; adjusted for body weight) followed by plasma glucose (PG) and pharmacokinetic blood sampling for 36 and 57 h, respectively. There were no apparent differences between age groups in PG lowering effect (AUCPGbaseline,0-6 h,meal,SD), maximum PG excursion (ΔPGmax,meal,SD), or maximum PG concentration (PGmax,meal,SD) after the standardized meal. Estimated ratios (ERs) for total exposure (AUCIAsp,0-12 h,SD) and maximum concentration (Cmax,IAsp,SD) of IAsp in IDegAsp were children/adults, 1.69 (95% confidence interval, CI: 1.02; 2.80) and 1.66 (95% CI: 1.10; 2.51); adolescents/adults, 1.14 (95% CI: 0.76; 1.69) and 1.16 (95% CI: 0.84; 1.61). ERs for total exposure (AUCIDeg,0-∞,SD) and maximum concentration (Cmax,IDeg,SD) of IDeg in IDegAsp were children/adults, 1.42 (95% CI: 0.94; 2.16) and 1.38 (95% CI: 1.09; 1.76); adolescents/adults, 1.23 (95% CI: 0.96; 1.58) and 1.16 (95% CI: 0.95; 1.42). IDegAsp was well tolerated across age groups. The fast onset of prandial coverage of IAsp in IDegAsp and the ultra-long pharmacokinetic properties of IDeg in IDegAsp were preserved in children and adolescents. Exposure to IAsp and IDeg seemed to be higher in children vs. adults, but no differences were observed in PG lowering effect. IDegAsp could be an alternative treatment option in children and adolescents with T1DM.
authors.affiliation: Diabetes Centre for Children and Adolescents, Kinder- und Jugendkrankenhaus AUF DER BULT, Hannover, Germany.
authors.forename: Torben
authors.initials: T
authors.lastname: Biester
authors.affiliation: Diabetes Centre for Children and Adolescents, Kinder- und Jugendkrankenhaus AUF DER BULT, Hannover, Germany. Danne@hka.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Danne
authors.affiliation: Diabetes Centre for Children and Adolescents, Kinder- und Jugendkrankenhaus AUF DER BULT, Hannover, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bläsig
authors.affiliation: Diabetes Centre for Children and Adolescents, Kinder- und Jugendkrankenhaus AUF DER BULT, Hannover, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Remus
authors.affiliation: Diabetes Centre for Children and Adolescents, Kinder- und Jugendkrankenhaus AUF DER BULT, Hannover, Germany.
authors.forename: Bärbel
authors.initials: B
authors.lastname: Aschemeier
authors.affiliation: Diabetes Centre for Children and Adolescents, Kinder- und Jugendkrankenhaus AUF DER BULT, Hannover, Germany.
authors.forename: Olga
authors.initials: O
authors.lastname: Kordonouri
authors.affiliation: Biostatistics, Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Bardtrum
authors.affiliation: Clinical Pharmacology, Novo Nordisk A/S, Søborg, Denmark.
authors.forename: Hanne
authors.initials: H
authors.lastname: Haahr
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism*; D004338:Drug Combinations; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D062407:Meals; D008875:Middle Aged; D055815:Young Adult
chemical_list: D004338:Drug Combinations; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; C578220:insulin degludec, insulin aspart drug combination
keywords: adolescents; children; insulin degludec - insulin aspart; pharmacodynamics; pharmacokinetics