Intravenous Dosing as an Alternate Approach to Safely Achieve Supratherapeutic Exposure for Assessments of Cardiac Repolarization: A Randomized Clinical Trial with Mavoglurant (AFQ056).

Purpose: The conduct of thorough QTc (TQT) studies is often challenging with compounds that are characterized by limited tolerability in healthy individuals. This is applicable to several central nervous system drugs, including mavoglurant acting as a selective allosteric modulator of metabotropic glutamate receptor 5. This TQT study describes the use of a single intravenous dosing regimen as an alternate approach allowing for sufficiently high C values while controlling tolerability.

Effect of Pradigastat, a Diacylglycerol Acyltransferase 1 Inhibitor, on the QTcF Interval in Humans.

Pradigastat, a novel diacylglycerol acyltransferase 1 inhibitor, has been studied in familial chylomicronemia syndrome. To evaluate the effects of supratherapeutic concentrations of pradigastat on the QTc interval, 2 studies were conducted. The first study assessed the safety, tolerability, and pharmacokinetics of single escalating intravenous doses of pradigastat (10, 30, 100, and 115 mg over 60 minutes) in healthy adults.

Relative bioavailability of diclofenac potassium from softgel capsule versus powder for oral solution and immediate-release tablet formulation.

The oral bioavailability of diclofenac potassium 50 mg administered as a soft gelatin capsule (softgel capsule), powder for oral solution (oral solution), and tablet was evaluated in a randomized, open-label, 3-period, 6-sequence crossover study in healthy adults. Plasma diclofenac concentrations were measured using a validated liquid chromatography-mass spectrometry/mass spectrometry method, and pharmacokinetic analysis was performed by noncompartmental methods. The median time to achieve peak plasma concentrations of diclofenac was 0.

Bioequivalence and food effect assessment for vildagliptin/metformin fixed-dose combination tablets relative to free combination of vildagliptin and metformin in Japanese healthy subjects.

Objective: To assess the bioequivalence of vildagliptin/metformin fixeddose combination (FDC) tablets (50/250 mg and 50/500 mg) to free combinations of vildagliptin and metformin and the effect of food on the pharmacokinetics (PK) of vildagliptin and metformin following administration of 50/500 mg FDC tablets.

Methods: Two openlabel, randomized, single-center, singledose, 2-period crossover studies were conducted in Japanese healthy male volunteers. Participants were administered vildagliptin/ metformin FDC tablets (study I: 50/250 mg, study II: 50/500 mg) or their free combinations under fasted condition.

Evaluation of a potential transporter-mediated drug interaction between rosuvastatin and pradigastat, a novel DGAT-1 inhibitor.

Objective: An in vitro drugdrug interaction (DDI) study was performed to assess the potential for pradigastat to inhibit breast cancer resistance protein (BCRP), organic anion-transporting polypeptide (OATP), and organic anion transporter 3 (OAT3) transport activities. To understand the relevance of these in vitro findings, a clinical pharmacokinetic DDI study using rosuvastatin as a BCRP, OATP, and OAT3 probe substrate was conducted.

Methods: The study used cell lines that stably expressed or over-expressed the respective transporters.

Assessment of pharmacokinetic drug-drug interaction between pradigastat and acetaminophen in healthy subjects.

Purpose: The purpose of this study was to evaluate the effect of pradigastat, a diacylglycerol acyltransferase-1 inhibitor, on the pharmacokinetics of acetaminophen, a gastric emptying marker.

Methods: Twenty-five healthy subjects were enrolled and received 1000 mg acetaminophen with meal in period 1, pradigastat (100 mg × 3 days followed by 40 mg × 7 days, 1 h before meal) in period 2, and 1000 mg acetaminophen at -2, -1, 0, +1, and +3 h with respect to meal timing in presence of steady-state pradigastat (40-mg maintenance dose) during periods 3-7.

Results: The geometric mean ratio and 90% confidence interval of Cmax and AUC of acetaminophen were within 80-125% suggesting that the rate ad extent of acetaminophen were not affected when given at various time points with respect to pradigastat/meal timing.