Maryam Fath1, Thomas Danne1, Torben Biester1, Lars Erichsen2, Olga Kordonouri1, Hanne Haahr3. 1. Diabetes Centre for Children and Adolescents, Kinder- und Jugendkrankenhaus AUF DER BULT, Hannover, Germany. 2. Biostatistics, Novo Nordisk A/S, Søborg, Denmark. 3. Clinical Pharmacology, Novo Nordisk A/S, Søborg, Denmark.
Abstract
BACKGROUND:Faster-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation with additional excipients (L-arginine and niacinamide). In adults, faster aspart provides faster onset and greater early exposure and action vs IAsp. AIM: This randomized, double-blind, 2-period crossover trial investigated the pharmacological properties of faster aspart vs IAsp in 12 children (6-11 years), 13 adolescents (12-17 years), and 15 adults (18-64 years) with type 1 diabetes mellitus. METHODS: Subjects received 0.2 U/kg subcutaneous dosing (mean of 8.3, 12.8, and 15.6 U, respectively) immediately prior to a standardized meal (17.3 g carbohydrate/100 mL; amount adjusted by body weight). RESULTS: Consistently across age groups, onset of appearance occurred approximately twice-as-fast (5-7 minutes earlier) and early exposure (AUCIAsp,0-30min ; area under the IAsp curve from 0 to 30 minutes) was greater (by 78%-147%) for faster aspart vs IAsp, with no treatment differences in total exposure (AUCIAsp,0-t ) or maximum concentration (C max ). Two-hour postmeal plasma glucose excursion was reduced for faster aspart vs IAsp (although only reaching statistical significance in children). In accordance with the absolute dose administered for each age group, AUCIAsp,0-t for faster aspart was lower in children (estimated ratio children/adults [95% confidence interval]: 0.59 [0.50;0.69], P < .001) and adolescents (0.78 [0.67;0.90], P = .002) vs adults. No age group differences were seen in C max (0.91 [0.70;1.17], P = .445, and 0.99 [0.77;1.26], P = .903). The age effect on AUCIAsp,0-t and C max did not differ statistically significantly between treatments. Faster aspart and IAsp were well-tolerated. CONCLUSION: The current findings in children and adolescents suggest a potential for faster aspart to improve postprandial glycemia over current rapid-acting insulins also in younger age groups. http://ClinicalTrials.gov identifier: NCT02035371.
RCT Entities:
BACKGROUND: Faster-acting insulinaspart (faster aspart) is insulinaspart (IAsp) in a new formulation with additional excipients (L-arginine and niacinamide). In adults, faster aspart provides faster onset and greater early exposure and action vs IAsp. AIM: This randomized, double-blind, 2-period crossover trial investigated the pharmacological properties of faster aspart vs IAsp in 12 children (6-11 years), 13 adolescents (12-17 years), and 15 adults (18-64 years) with type 1 diabetes mellitus. METHODS: Subjects received 0.2 U/kg subcutaneous dosing (mean of 8.3, 12.8, and 15.6 U, respectively) immediately prior to a standardized meal (17.3 g carbohydrate/100 mL; amount adjusted by body weight). RESULTS: Consistently across age groups, onset of appearance occurred approximately twice-as-fast (5-7 minutes earlier) and early exposure (AUCIAsp,0-30min ; area under the IAsp curve from 0 to 30 minutes) was greater (by 78%-147%) for faster aspart vs IAsp, with no treatment differences in total exposure (AUCIAsp,0-t ) or maximum concentration (C max ). Two-hour postmeal plasma glucose excursion was reduced for faster aspart vs IAsp (although only reaching statistical significance in children). In accordance with the absolute dose administered for each age group, AUCIAsp,0-t for faster aspart was lower in children (estimated ratio children/adults [95% confidence interval]: 0.59 [0.50;0.69], P < .001) and adolescents (0.78 [0.67;0.90], P = .002) vs adults. No age group differences were seen in C max (0.91 [0.70;1.17], P = .445, and 0.99 [0.77;1.26], P = .903). The age effect on AUCIAsp,0-t and C max did not differ statistically significantly between treatments. Faster aspart and IAsp were well-tolerated. CONCLUSION: The current findings in children and adolescents suggest a potential for faster aspart to improve postprandial glycemia over current rapid-acting insulins also in younger age groups. http://ClinicalTrials.gov identifier: NCT02035371.
Authors: Bruce W Bode; Violeta Iotova; Margarita Kovarenko; Lori M Laffel; Paturi V Rao; Srikanth Deenadayalan; Magnus Ekelund; Steffen Falgreen Larsen; Thomas Danne Journal: Diabetes Care Date: 2019-05-10 Impact factor: 19.112
Authors: Joseph L Mann; Caitlin L Maikawa; Anton A A Smith; Abigail K Grosskopf; Sam W Baker; Gillie A Roth; Catherine M Meis; Emily C Gale; Celine S Liong; Santiago Correa; Doreen Chan; Lyndsay M Stapleton; Anthony C Yu; Ben Muir; Shaun Howard; Almar Postma; Eric A Appel Journal: Sci Transl Med Date: 2020-07-01 Impact factor: 17.956