In:
British Journal of Clinical Pharmacology, Wiley, Vol. 78, No. 6 ( 2014-12), p. 1407-1418
Abstract:
To provide model‐based clinical development decision support including dose selection guidance for empagliflozin, an orally administered sodium glucose cotransporter 2 inhibitor, through developed exposure−response ( E−R ) models for efficacy and tolerability in patients with type 2 diabetes mellitus ( T2DM ). Methods Five randomized, placebo‐controlled, multiple oral dose studies of empagliflozin in patients with T2DM ( n = 974; 1–100 mg once daily, duration ≤12 weeks) were used to develop E−R models for efficacy (glycosylated haemoglobin [ HbA 1c ], fasting plasma glucose [ FPG ] and urinary glucose excretion). Two studies ( n = 748, 12 weeks) were used to evaluate tolerability E−R . Results The efficacy model predicted maximal decreases in FPG and HbA 1c of 16% and 0.6%, respectively, assuming a baseline FPG concentration of 8 m m (144 mg dl −1 ) and 10–25 mg every day empagliflozin targeted 80–90% of these maximums. Increases in exposure had no effect on incidence rates of hypoglycaemia ( n = 4), urinary tract infection ( n = 17) or genital/vulvovaginal‐related ( n = 16) events, although low prevalence rates may have precluded more accurate evaluation. Conclusions E−R analyses indicated that 10 and 25 mg once daily empagliflozin doses achieved near maximal glucose lowering efficacy.
Type of Medium:
Online Resource
ISSN:
0306-5251
,
1365-2125
DOI:
10.1111/bcp.2014.78.issue-6
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
1498142-7
SSG:
15,3
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