The effects of NN414, a SUR1/Kir6.2 selective potassium channel opener, in healthy male subjects.
The aim of the present study was to investigate the effect of a single dose of NN414 (a selective SUR1/Kir6.2 potassium channel opener). Sixty-four healthy male subjects were enrolled at 8 dose levels (0.625-12.5 mg/kg or placebo). The study consisted of a baseline day and a dosing day. NN414 or placebo was administered in the evening about 10 pm. On both study days, an oral glucose tolerance test (OGTT) was performed following an overnight fast (corresponding to 9 hours postdose), and glucose, insulin, glucagon, and growth hormone concentrations were determined. NN414 was well tolerated, with no clinically relevant changes in safety parameters, although there was an increase in gastrointestinal side effects. NN414 treatment lowered glucose during the OGTT and 24-hour insulin and glucose levels. In conclusion, a single dose of NN414 is associated with improvements in glucose-related parameters in healthy male subjects.
Zdravkovic
Milan
M
Novo Nordisk A/S, Medical Development, Bagsvaerd, Denmark.
Kruse
Matthias
M
Rost
Karl Ludwig
KL
Møss
Judi
J
Kecskes
Andrei
A
Dyrberg
Thomas
T
D018528:ATP-Binding Cassette Transporters / Q000187:drug effects / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D003499:Cyclic S-Oxides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000378:metabolism; D011955:Receptors, Drug / Q000187:drug effects / Q000378:metabolism; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel
D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003499:Cyclic S-Oxides; D007328:Insulin; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577507:ABCC8 protein, human; C475618:NN 414