Dataset Information

Pharmacokinetics, Safety and Tolerability of Oral Semaglutide in Subjects with Renal Impairment.

ABSTRACT: BACKGROUND:Semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, has been co-formulated with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC) as a tablet for oral administration. This trial (NCT02014259) investigated the pharmacokinetics, safety and tolerability of oral semaglutide in subjects with and without renal impairment. METHODS:Subjects were categorised as having normal renal function (n?=?24), mild (n?=?12), moderate (n?=?12) or severe (n?=?12) renal impairment, or end-stage renal disease (ESRD) requiring haemodialysis (n?=?11) and received once-daily oral semaglutide (5 mg for 5 days followed by 10 mg for 5 days) in the fasting state, followed by 30 min fasting after dosing. Semaglutide plasma concentrations were measured during dosing and for up to 21 days after the last dose. RESULTS:Semaglutide exposure (area under the plasma concentration-time curve from time zero to 24 h after the tenth dose and maximum concentration after the tenth dose) did not vary in a consistent pattern across the renal function groups. Similarly, there was no apparent effect of renal impairment on the semaglutide half-life (geometric mean range 152-165 h). Except for one subject in the ESRD group, semaglutide was not detected in urine. Haemodialysis did not affect the pharmacokinetics of semaglutide. Adverse events were in line with those observed for other GLP-1 receptor agonists and no safety concerns were identified. CONCLUSION:There was no apparent effect of renal impairment or haemodialysis on the pharmacokinetics of oral semaglutide. Based on this trial, renal impairment should not affect dose recommendations for oral semaglutide.

SUBMITTER: Granhall C

PROVIDER: S-EPMC6267549 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pharmacokinetics, Safety and Tolerability of Oral Semaglutide in Subjects with Renal Impairment.

Granhall Charlotte C Søndergaard Flemming L FL Thomsen Mette M Anderson Thomas W TW

Clinical pharmacokinetics 20181201 12

<h4>Background</h4>Semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, has been co-formulated with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC) as a tablet for oral administration. This trial (NCT02014259) investigated the pharmacokinetics, safety and tolerability of oral semaglutide in subjects with and without renal impairment.<h4>Methods</h4>Subjects were categorised as having normal renal function (n = 24), mild (n = 12), moderate (n = 12) or severe (n ...[more]

PMID: 29623579

Similar Datasets

Project description:Sulbactam-durlobactam is being developed for the treatment of infections caused by Acinetobacter baumannii, including those caused by multidrug- and carbapenem-resistant isolates. This was a phase 1 study to evaluate the effects of various degrees of renal impairment, including subjects with end-stage renal disease (ESRD) on hemodialysis (HD), on the pharmacokinetics and safety profile of durlobactam (also known as ETX2514) and sulbactam after single intravenous (i.v.) dose administration. For healthy subjects and those with mild or moderate renal impairment (RI), single 1,000-mg doses each of durlobactam and sulbactam via a 3-h i.v. infusion were administered, and for severe renal impairment, 500-mg doses were administered. For subjects with ESRD and HD, 500-mg i.v. doses each of durlobactam and sulbactam were administered post-HD and pre-HD, with a 1-week washout between doses. Among 34 subjects, decreasing renal function increased systemic exposure (peak plasma concentration [Cmax] and area under the concentration-time curve [AUC]) to durlobactam and sulbactam in a generally linear manner. In healthy subjects and in those with mild or moderate renal impairment, the majority of durlobactam and sulbactam was excreted in the urine, while approximately 40% or less was excreted in urine in subjects with severe renal impairment or ESRD. In subjects with ESRD, hemodialysis was effective at removing both durlobactam and sulbactam from plasma. Renal impairment had no effect of the safety/tolerability profile of durlobactam and sulbactam. In summary, RI and ESRD had a predictable effect on the pharmacokinetic (PK) profile of durlobactam and sulbactam with no adverse effects on the safety/tolerability profile. Durlobactam and sulbactam are cleared to a similar extent by renal elimination and are impacted similarly by renal impairment. The results from this study have been used with population PK modeling and nonclinically derived PK/PD (pharmacodynamic) exposure targets to establish dosage recommendations for durlobactam and sulbactam in patients with various degrees of RI. The dosing regimen of durlobactam-sulbactam will require adjustment in patients with severe renal insufficiency and in those with ESRD.

Project description:AIMS:To investigate whether the pharmacokinetic characteristics of semaglutide were altered in people with hepatic impairment, assessed using Child-Pugh criteria, vs those with normal hepatic function. METHODS:In this multicentre, open-label, parallel-group trial (sponsor Novo Nordisk, ClinicalTrials.gov ID NCT02210871), four groups of participants with normal hepatic function (n?=?19) or mild (n?=?8), moderate (n?=?10) or severe (n?=?7) hepatic impairment received a single, subcutaneous dose of 0.5 mg semaglutide. Semaglutide plasma concentrations were assessed frequently for 35?days after dosing. The primary endpoint was area under the semaglutide plasma concentration-time curve from time zero to infinity (AUC0-? ). No effect of hepatic impairment was declared if the 90% confidence interval (CI) for the between-group ratio (hepatic impairment/normal function) was within the interval 0.70 to 1.43. RESULTS:Semaglutide exposure was similar across all groups, with AUC0-? treatment ratios for mild impairment/normal function of 0.95 (90% CI 0.77, 1.16), moderate impairment/normal function 1.02 (90% CI 0.93, 1.12), and severe impairment/normal function 0.97 (90% CI 0.84, 1.12). The maximum plasma semaglutide concentration (Cmax ) did not appear to be influenced by hepatic function, with mild impairment/normal function treatment ratios of 0.99 (90% CI 0.80, 1.23), moderate impairment/normal function 1.02 (90% CI 0.88, 1.18) and severe impairment/normal function 1.15 (90% CI 0.89, 1.48; sensitivity analysis excluding one extreme semaglutide concentration: 1.05 [90% CI 0.88, 1.25]). In all, 10 participants reported 12 mild or moderate non-serious adverse events. No unexpected safety or tolerability issues were observed. CONCLUSIONS:Semaglutide exposure did not appear to be affected by hepatic impairment, suggesting that dose adjustment may not be necessary in patients with hepatic impairment. Semaglutide was well tolerated and there were no unexpected safety issues.

Dataset Information

Pharmacokinetics, Safety and Tolerability of Oral Semaglutide in Subjects with Renal Impairment.

Publications

Pharmacokinetics, Safety and Tolerability of Oral Semaglutide in Subjects with Renal Impairment.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets