Dataset Information

The pharmacokinetics and pharmacodynamics of alogliptin in children, adolescents, and adults with type 2 diabetes mellitus.

ABSTRACT:

Purpose

The aim of this study is to determine the pharmacokinetics (PK) and pharmacodynamics (PD) of a single 12.5- or 25-mg dose of alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, in pediatric (children and adolescents) and adult subjects with type 2 diabetes mellitus (T2DM).

Methods

A randomized, open-label, multicenter study was conducted in pediatric and adult subjects. Subjects in two pediatric groups (children and adolescents) were randomized 1:1 to receive a single oral dose of alogliptin 12.5 or 25 mg, respectively; all gender- and race-matched adult subjects received alogliptin 25 mg. Blood and urine samples were collected at prespecified time points for PK/PD analyses. A PK/PD model was developed using data from the study for steady-state simulations. Safety was also assessed.

Results

In pediatric subjects receiving the 25-mg dose, the mean alogliptin peak plasma concentrations (C_max) and AUC_0-inf values were 26 and 23% lower, respectively, than in adults receiving the 25-mg dose, but maximum observed DPP-4 inhibition effect (E_max) and AUEC_0-24 values were similar to those in adults. In pediatric subjects receiving the 12.5-mg dose, the mean alogliptin C_max and AUC_0-inf values were 58 and 54% lower, respectively, than those in adults, hence E_max and AUEC_0-24 values were also lower by 11 and 17%, respectively. The PK/PD model simulated data were consistent with study results. No safety concern was found.

Conclusions

A 25-mg dose of alogliptin in pediatric subjects achieved alogliptin exposures and DPP-4 inhibition similar to those in adult T2DM patients without safety concerns; therefore, this dose is recommended for a pediatric phase 3 trial.

SUBMITTER: Dudkowski C

PROVIDER: S-EPMC5306220 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Publications

The pharmacokinetics and pharmacodynamics of alogliptin in children, adolescents, and adults with type 2 diabetes mellitus.

Dudkowski Caroline C Tsai Max M Liu Jie J Zhao Zhen Z Schmidt Eric E Xie Jeannie J

European journal of clinical pharmacology 20161220 3

<h4>Purpose</h4>The aim of this study is to determine the pharmacokinetics (PK) and pharmacodynamics (PD) of a single 12.5- or 25-mg dose of alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, in pediatric (children and adolescents) and adult subjects with type 2 diabetes mellitus (T2DM).<h4>Methods</h4>A randomized, open-label, multicenter study was conducted in pediatric and adult subjects. Subjects in two pediatric groups (children and adolescents) were randomized 1:1 to receive a single ...[more]

PMID: 27999883

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Project description:IntroductionCanagliflozin is a sodium glucose co-transporter 2 inhibitor approved worldwide for the treatment of patients with type 2 diabetes mellitus (T2DM). The present study evaluated pharmacokinetics, pharmacodynamics, and safety of canagliflozin in Japanese patients with T2DM.MethodsCanagliflozin, at doses of 25, 100, 200, or 400 mg, was administered as a single dose and, after a washout of 1 day, in repeated doses for 14 consecutive days to 61 subjects in a randomized, double-blind, placebo-controlled study. Plasma concentrations of canagliflozin and urinary glucose excretion (UGE) were measured, and renal threshold for glucose excretion (RTG) was calculated. Safety was evaluated on the basis of adverse event (AE) reports, blood and urine laboratory parameters, and vital signs.ResultsPlasma canagliflozin maximum concentration and area under the concentration-time curve (AUC) values increased in a dose-dependent manner with the time to maximum concentration (t max) of 1.0 h and elimination half-life (t 1/2) of 10.22-13.26 h on Day 1. No significant changes in t max and t 1/2 were observed after multiple-dose administration. The linearity factors, as calculated from the ratios of AUC0-24h on Day 16 to AUC0-∞ on Day 1, were close to 1 in all canagliflozin groups. Canagliflozin increased UGE0-24h (80-110 g/day with canagliflozin ≥100 mg) and decreased RTG from the first day of treatment; these effects were sustained during the entire period of multiple administration. No significant AEs were noted. Urine volume was slightly increased on Day 1, but subsequent changes after repeated doses for 14 days were small. Urinary sodium tended to be higher in the early treatment period, whereas no particular change was observed in serum osmolality and hematocrit.ConclusionCanagliflozin increased UGE, decreased RTG, and was well tolerated throughout the entire period of multiple administrations in Japanese patients with T2DM.FundingMitsubishi Tanabe Pharma Corporation.Trial registrationClinicalTrials.gov#NCT00707954.

Dataset Information

The pharmacokinetics and pharmacodynamics of alogliptin in children, adolescents, and adults with type 2 diabetes mellitus.

Purpose

Methods

Results

Conclusions

Publications

The pharmacokinetics and pharmacodynamics of alogliptin in children, adolescents, and adults with type 2 diabetes mellitus.

Similar Datasets

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