Six-month safety evaluation of robenacoxib tablets (Onsior™) in dogs after daily oral administrations.

Background: Robenacoxib is a non-steroidal anti-inflammatory drug available for canine and feline use for the control of pain and inflammation marketed as Onsior™. The aim of this target animal safety study was to evaluate the 6-month safety profile of oral robenacoxib administration. It was a randomized, negative-controlled, parallel group study.

Nicotine pharmacokinetic profiles of the Tobacco Heating System 2.2, cigarettes and nicotine gum in Japanese smokers.

Two open-label randomized cross-over studies in Japanese smokers investigated the single-use nicotine pharmacokinetic profile of the Tobacco Heating System (THS) 2.2, cigarettes (CC) and nicotine replacement therapy (Gum). In each study, one on the regular and one on the menthol variants of the THS and CC, both using Gum as reference, 62 subjects were randomized to four sequences: Sequence 1: THS - CC (n = 22); Sequence 2: CC - THS (n = 22); Sequence 3: THS - Gum (n = 9); Sequence 4: Gum - THS (n = 9).

Evaluation of Nicotine Pharmacokinetics and Subjective Effects following Use of a Novel Nicotine Delivery System.

Introduction: Novel nicotine delivery systems represent an evolving part of the tobacco harm reduction strategy. The pharmacokinetic (PK) profile of nicotine delivered by P3L, a pulmonary nicotine delivery system, and its effects on smoking urges and craving relief in relation to Nicorette inhalator were evaluated.

Methods: This open-label, ascending nicotine levels study was conducted in 16 healthy smokers.

Nicotine Population Pharmacokinetics in Healthy Adult Smokers: A Retrospective Analysis.

Background And Objective: Characterizing nicotine pharmacokinetics is challenging in the presence of background exposure. We performed a combined retrospective population pharmacokinetic analysis of 8 trials, including exposure to Tobacco Heating System and cigarettes (both inhaled), nicotine nasal spray and oral nicotine gum.

Method: Data from 4 single product use trials were used to develop a population pharmacokinetic model with Phoenix NLME™ and to derive exposure parameters.

Three different up-titration regimens of ponesimod, an S1P1 receptor modulator, in healthy subjects.

Ponesimod is a selective S1P1 receptor modulator, and induces dose-dependent reduction of circulating lymphocytes upon oral dosing. Previous studies showed that single doses up to 75 mg or multiple doses up to 40 mg once daily are well tolerated, and heart rate (HR) reduction and atrio-ventricular conduction delays upon treatment initiation are reduced by gradual up-titration to the maintenance dose. This single-center, open-label, randomized, multiple-dose, 3-treatment, 3-way crossover study compared the tolerability, safety, pharmacokinetics, cardiodynamics, and effects on lymphocytes of 3 different up-titration regimens of ponesimod in healthy male and female subjects.

Differential effects of ponesimod, a selective S1P1 receptor modulator, on blood-circulating human T cell subpopulations.

Ponesimod, a novel selective sphingosine-1-phosphate 1 receptor modulator in the development for the treatment of autoimmune diseases, dose-dependently reduced lymphocyte counts in peripheral blood of healthy subjects. It rapidly and transiently reduced the number of circulating T and B cells, but not natural killer cells. T lymphocyte subsets exhibited differential sensitivities with a maximum decrease from baseline ranging from 67% to 89% following high doses.

Effects of ethnicity and sex on the pharmacokinetics and pharmacodynamics of the selective sphingosine-1-phosphate receptor 1 modulator ponesimod: a clinical study in Japanese and Caucasian subjects.

The aim of this study was to evaluate the relative pharmacokinetic (PK) and pharmacodynamic (PD) properties of a single dose of ponesimod, an oral and selective sphingosine-1-phosphate receptor 1 (S1P1) modulator, in Japanese and Caucasian healthy subjects and explore the effects of sex on PK. Subjects received a single 40-mg dose of ponesimod in a single-centre, open-label, parallel-group study design. Ten Japanese and 10 Caucasian healthy subjects (age: 22-45 years, 1:1 sex ratio) participated in the study and were matched for body weight (±10%).

Effect of ponesimod, a selective S1P1 receptor modulator, on the QT interval in healthy individuals.

Ponesimod is an orally active selective sphingosine-1-phosphate receptor 1 modulator under investigation for the treatment of multiple sclerosis. This was a single-centre, double-blind, randomized, placebo- and positive-controlled parallel-group study investigating the effects of ponesimod on the QTc interval in healthy individuals. A nested cross-over comparison between moxifloxacin and placebo was included in the combined moxifloxacin/placebo treatment group.

Mass balance, pharmacokinetics and metabolism of the selective S1P1 receptor modulator ponesimod in humans.

1. Ponesimod [(R)-5-[3-chloro-4-(-2,3-dihydroxy-propoxy)-benzylidene]-2-propylimino-3-o-tolyl-thiazolidin-4-one] is an orally administered, selective S1P1 receptor modulator that blocks the egress of lymphocytes from lymphoid organs and reduces the availability of circulating effector T/B-cells. 2.

Population pharmacokinetics and pharmacodynamics of ponesimod, a selective S1P1 receptor modulator.

Ponesimod (ACT-128800), a reversible, orally active, selective S1P1 receptor modulator, prevents the egress of lymphocytes from the lymph node into the systemic circulation. It is currently in clinical development for the treatment of relapsing multiple sclerosis. Modulation of circulating lymphocytes serves as biomarker of efficacy and safety, such that the quantitative characterization of the pharmacokinetic/pharmacodynamic (PK/PD) relationship guides the clinical development of the compound.

Effects of ponesimod, a selective S1P1 receptor modulator, on the pharmacokinetics of a hormonal combination contraceptive.

Purpose: To determine the effects of steady-state concentrations of the selective S1P1 receptor modulator ponesimod on the pharmacokinetics (PK) of a single dose of a combined oral contraceptive, containing 1 mg norethisterone (NET) and 35 μg ethinyl estradiol (EE) and to investigate the effects on heart rate at different ponesimod doses within an up-titration regimen prior to co-administration of the contraceptive.

Methods: Twenty-two healthy women (age: 29-60 years) received twice a single oral dose of the combined oral contraceptive, alone or in combination with multiple doses of 40 mg ponesimod attained by an up-titration regimen. Heart rate (HR) effects were assessed on the first day of each up-titration level.

Pharmacokinetics and pharmacodynamics of ponesimod, a selective S1P1 receptor modulator, in the first-in-human study.

Aims: This study investigated the tolerability, safety, pharmacokinetics and pharmacodynamics of ponesimod, a novel oral selective sphingosine-1-phosphate (S1P1) receptor modulator in development for the treatment of auto-immune diseases.

Methods: This was a double-blind, placebo-controlled, ascending, single-dose study. Healthy male subjects received doses of 1-75 mg or placebo control.