Effect of Renal Impairment on the Pharmacokinetics, Efficacy, and Safety of Albiglutide
Autor: | Jessica E. Matthews, Jeffrey A. Wald, Malcolm A. Young, Fred Yang, Rickey R. Reinhardt |
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Rok vydání: | 2014 |
Předmět: |
Adult
Male medicine.medical_specialty medicine.medical_treatment Population Renal function Blood Pressure Severity of Illness Index Gastroenterology Double-Blind Method Pharmacokinetics Glucagon-Like Peptide 1 Diabetes mellitus Internal medicine Severity of illness Humans Hypoglycemic Agents Multicenter Studies as Topic Medicine education Aged Randomized Controlled Trials as Topic Glycated Hemoglobin education.field_of_study Dose-Response Relationship Drug business.industry General Medicine Middle Aged medicine.disease Albiglutide Surgery Diabetes Mellitus Type 2 Area Under Curve Kidney Failure Chronic Female Hemodialysis business Glomerular Filtration Rate Kidney disease |
Zdroj: | Postgraduate Medicine. 126:35-46 |
ISSN: | 1941-9260 0032-5481 |
Popis: | Chronic kidney disease is frequently present in patients with type 2 diabetes mellitus (T2DM). New therapeutic options in this patient subpopulation are needed.Assess the effect of renal impairment on the pharmacokinetics (PK), efficacy, and safety of albiglutide in single- and multiple-dose studies.Pharmacokinetics, safety, and efficacy of once weekly albiglutide in patients with T2DM was assessed from a single-dose (30 mg), nonrandomized, open-label study (N = 41) including subjects with normal and varying degrees of renal impairment, including hemodialysis, and a pooled analysis of 4 phase 3, randomized, double-blind (1 open-label), active or placebo-controlled multiple-dose studies. The pooled analysis of the latter 4 studies (N = 1113) was part of the population PK analysis, which included subjects with normal and varying degrees of renal impairment (mild, moderate, severe) treated with albiglutide (30 to 50 mg) to primary end points of 26 to 52 weeks.Single-dose PK showed area-under-the-curve ratios (and 90% CIs) of 1.32 (0.96-1.80), 1.39 (1.03-1.89), and 0.99 (0.63-1.57) for the moderate, severe, and hemodialysis groups, respectively, relative to the normal group. Results indicate that modest increases in plasma concentration of albiglutide were observed with the severity of renal impairment. There was a trend for more glycemic lowering as the estimated glomerular filtration rate decreased. The severe group had a higher frequency of gastrointestinal (eg, diarrhea, constipation, nausea, and vomiting) and hypoglycemic (with background sulfonylurea use) events compared with patients with mild or moderate renal impairment.The PK, efficacy, and safety data indicate that albiglutide has a favorable benefit/risk ratio in patients with T2DM and varying degrees of renal impairment, and the need for a dose adjustment is not suggested. Experience in patients with more severe renal impairment is very limited, so the recommendation is to use albiglutide carefully in this population.(ClinicalTrials.gov):NCT00938158, NCT00849017, NCT00838916, NCT00839527, NCT0198539. |
Databáze: | OpenAIRE |
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