Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of a Single-Dose of NN2211, a Long-Acting Glucagon-Like Peptide 1 Derivative, in Healthy Male Subjects Export

@article{citeulike:785486, abstract = {OBJECTIVE--The primary objective of the present study was to investigate the safety, tolerability, and pharmacokinetics of a single dose of NN2211, a long-acting glucagon-like peptide 1 (GLP-1) derivative, in healthy male subjects. The secondary objective was to investigate the pharmacodynamics of NN2211. RESEARCH DESIGN AND METHODS--In a double-blind, randomized dose, escalation, placebo-controlled study, healthy male subjects were enrolled at eight consecutive dose levels (1.25, 2.5, 5.0, 10.0, 12.5, 15.0, 17.5, and 20.0 {micro}g/kg) with eight subjects per dose level at a 3:1 active:placebo randomization. After subcutaneous dosing with NN2211, 48-h pharmacokinetic, and 24-h glucose, insulin and glucagon profiles were assessed. In addition, three subjects at each dose level were randomly assigned (one placebo/two active) to an intravenous glucose tolerance test (IVGTT) 9 h after the dose (corresponding to the time to maximal plasma concentration of NN2211). RESULTS--After subcutaneous administration, the half-life of NN2211 was found to be 11-15 h. Overall, although there were no statistically significant differences compared with placebo in the area under the curve (0-9 h for insulin or glucagon), there was a borderline- significant lowering of glucose levels (P = 0.066). During the IVGTT, there was a statistically significant increase in insulin secretion (P = 0.0002), but there was no significant effect on glucagon levels. Although no significant effect was observed on glucose levels during the IVGTT, there was a dose-dependent increase in the glucose disappearance constant. Whereas no serious adverse events were observed, there was a higher incidence of adverse events after active treatment compared with placebo treatment (notably headache, dizziness, nausea, and vomiting). CONCLUSIONS--This study provides evidence that NN2211 has a pharmacokinetic profile consistent with once-daily dosing in humans.}, author = {Elbrond, Bodil and Jakobsen, Grethe and Larsen, Soren and Agerso, Henrik and Jensen, Lisbeth B. and Rolan, Paul and Sturis, Jeppe and Hatorp, Vibeke and Zdravkovic, Milan}, citeulike-article-id = {785486}, citeulike-linkout-0 = {http://care.diabetesjournals.org/cgi/content/abstract/25/8/1398}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/12145241}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=12145241}, day = {1}, journal = {Diabetes Care}, keywords = {1, 2002, biosci353, derivative, diabetes, glucagon-like, liraglutide, peptide}, month = {August}, number = {8}, pages = {1398--1404}, posted-at = {2006-08-04 03:57:36}, priority = {3}, title = {Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of a Single-Dose of NN2211, a Long-Acting Glucagon-Like Peptide 1 Derivative, in Healthy Male Subjects}, url = {http://care.diabetesjournals.org/cgi/content/abstract/25/8/1398}, volume = {25}, year = {2002} }

TY - JOUR ID - citeulike:785486 L3 - citeulike-article-id:785486 N2 - OBJECTIVE--The primary objective of the present study was to investigate the safety, tolerability, and pharmacokinetics of a single dose of NN2211, a long-acting glucagon-like peptide 1 (GLP-1) derivative, in healthy male subjects. The secondary objective was to investigate the pharmacodynamics of NN2211. RESEARCH DESIGN AND METHODS--In a double-blind, randomized dose, escalation, placebo-controlled study, healthy male subjects were enrolled at eight consecutive dose levels (1.25, 2.5, 5.0, 10.0, 12.5, 15.0, 17.5, and 20.0 {micro}g/kg) with eight subjects per dose level at a 3:1 active:placebo randomization. After subcutaneous dosing with NN2211, 48-h pharmacokinetic, and 24-h glucose, insulin and glucagon profiles were assessed. In addition, three subjects at each dose level were randomly assigned (one placebo/two active) to an intravenous glucose tolerance test (IVGTT) 9 h after the dose (corresponding to the time to maximal plasma concentration of NN2211). RESULTS--After subcutaneous administration, the half-life of NN2211 was found to be 11-15 h. Overall, although there were no statistically significant differences compared with placebo in the area under the curve (0-9 h for insulin or glucagon), there was a borderline- significant lowering of glucose levels (P = 0.066). During the IVGTT, there was a statistically significant increase in insulin secretion (P = 0.0002), but there was no significant effect on glucagon levels. Although no significant effect was observed on glucose levels during the IVGTT, there was a dose-dependent increase in the glucose disappearance constant. Whereas no serious adverse events were observed, there was a higher incidence of adverse events after active treatment compared with placebo treatment (notably headache, dizziness, nausea, and vomiting). CONCLUSIONS--This study provides evidence that NN2211 has a pharmacokinetic profile consistent with once-daily dosing in humans. IS - 8 JF - Diabetes Care EP - 1404 TI - Pharmacokinetics, Pharmacodynamics, Safety, and Tolerability of a Single-Dose of NN2211, a Long-Acting Glucagon-Like Peptide 1 Derivative, in Healthy Male Subjects VL - 25 SP - 1398 KW - 1 KW - 2002 KW - biosci353 KW - derivative KW - diabetes KW - glucagon-like KW - liraglutide KW - peptide AU - Elbrond, Bodil AU - Jakobsen, Grethe AU - Larsen, Soren AU - Agerso, Henrik AU - Jensen, Lisbeth AU - Rolan, Paul AU - Sturis, Jeppe AU - Hatorp, Vibeke AU - Zdravkovic, Milan PY - 2002/08/01/ UR - http://care.diabetesjournals.org/cgi/content/abstract/25/8/1398 ER -