Modified release terbutaline (SKP1052) for hypoglycaemia prevention: a proof-of-concept study in people with type 1 diabetes mellitus

Nosek, L., Cardot, J.-M., Owens, David Raymond, Ibarra, P., Bagate, K., Vergnault, G., Kaiser, K., Fischer, A. and Heise, T. 2012. Modified release terbutaline (SKP1052) for hypoglycaemia prevention: a proof-of-concept study in people with type 1 diabetes mellitus. Diabetes, Obesity and Metabolism 14 (12) , pp. 1137-1144. 10.1111/dom.12003

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Abstract

Aims: In this randomized, single blind, cross-over study 2.5mg and 5mg of the modified-release terbutaline formulation (SKP-1052) were compared with conventional immediate-release terbutaline (IRT, 5mg) and placebo on overnight blood glucose (BG) and hypoglycaemia in 30 subjects with type 1 diabetes mellitus. Methods: Subjects received subcutaneous injections of insulin glargine (individualized doses) before dinner. SKP-1052, IRT or placebo was administered around 21:00 hours. BG and terbutaline concentrations were monitored overnight for 10 h post-dosing. Endpoints comprised of the nadir BG (BGn 0–10 h, primary endpoint), mean overnight BG (BGmean), morning BG (BGmorning) and hypoglycaemia rates as well as pharmacokinetic (PK) endpoints. Results: SKP-1052 delayed release of terbutaline by 2 h [PK-tmax (mean±SD) 5.0±2.1 h (2.5 mg) and 4.7±1.7 h (5 mg) vs. 2.6±1.3 h with IRT, p<0.01, respectively]. Compared with placebo, no significant differences were observed for BGn 0–10 h across treatments, but both 5 mg formulations showed less hypoglycaemic events [10 (IRT), 16 (SKP-1052) vs. 33], higher BGmean (120, 114 and 95mg/dl) and BGmorning (126, 126 and 101 mg/dl, all comparisons p<0.05 vs. placebo). Numerically higher BG-levels between 3 and 8 h post-dosing were observed with 2.5mg SKP-1052 vs. placebo. Conclusions: Compared with IRT SKP-1052 delays release of terbutaline. 2.5mg SKP-1052 led to numerically higher BG 3 to 8 h post-dose without fasting hyperglycaemia while 5 mg SKP-1052 resulted in fasting hyperglycaemia vs. placebo. Future studies will investigate optimized doses of SKP-1052 for nocturnal hypoglycaemia prevention.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General) R Medicine > RM Therapeutics. Pharmacology
Uncontrolled Keywords:	adverse drug reactions, diabetes complications, experimental pharmacology, glucose metabolism, insulin therapy, phase III study
Publisher:	Wiley and Blackwell
ISSN:	1462-8902
Last Modified:	04 Jun 2017 04:40
URI:	https://orca.cardiff.ac.uk/id/eprint/42709

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