Efficacy and safety of olezarsen in lowering apolipoprotein C-III and triglycerides in healthy Japanese Americans.

Background: Olezarsen is a GalNAc-conjugated, hepatic-targeted antisense oligonucleotide that lowers apolipoprotein C-III (apoC-III) and triglyceride levels. The efficacy and safety of olezarsen has not previously been studied in ethnically diverse American populations. The aim of this study is to assess the effect of olezarsen in healthy Japanese Americans.

Efficacy and safety of pelacarsen in lowering Lp(a) in healthy Japanese subjects.

Background: Pelacarsen is a liver-targeted antisense oligonucleotide that potently lowers lipoprotein(a) [Lp(a)] levels. Its safety and efficacy in diverse populations has not been extensively studied.

Objective: To assess the effect of pelacarsen, including monthly dosing of 80 mg, in subjects of Japanese ancestry.

A Randomized, Controlled Phase I/II Study to Evaluate the Safety and Efficacy of MGV354 for Ocular Hypertension or Glaucoma.

Purpose: To assess the clinical safety, tolerability, and efficacy of topically administered MGV354, a soluble guanylate cyclase (sGC) activator, in patients with ocular hypertension (OH) or glaucoma.

Design: Double-masked, randomized, and vehicle-controlled study.

Methods: Parts 1 and 2 evaluated safety and tolerability to identify the maximum tolerated dose (MTD) of once-daily MGV354 in 32 healthy volunteers (Part 1) and 16 patients with OH or glaucoma (Part 2) at a single clinical site.

Absence of irreversible effects of aliskiren in standard juvenile rat toxicity studies.

Background: Aliskiren is the first orally bioavailable direct renin inhibitor approved for the treatment of hypertension in adults. Juvenile toxicity studies in rats were initiated to support treatment in the pediatric population.

Methods: In Study 1, aliskiren oral administration was initiated on postpartum day (PPD) 14, after nephrogenesis was completed, and continued through PPD 70 at doses of 0, 30, 100, and 300 mg/kg/day.

Pharmacokinetic and pharmacodynamic drug-drug interaction assessment between pradigastat and digoxin or warfarin.

Pradigastat, a novel diacylglycerol acyltransferase-1 inhibitor, was evaluated for both pharmacokinetic (PK) and pharmacodynamic (PD) drug-drug interactions when co-administered with digoxin or warfarin in healthy subjects. This open-label study included two parallel subject cohorts each with three sequential treatment periods. Forty subjects were enrolled in the study with 20 subjects allocated to each cohort.

Aliskiren toxicity in juvenile rats is determined by ontogenic regulation of intestinal P-glycoprotein expression.

Juvenile rat toxicity studies with the direct renin inhibitor aliskiren were initiated to support treatment in the pediatric population. In Study 1, aliskiren was administered orally to juvenile rats at doses of 0, 30, 100 or 300 mg/kg/day with repeated dosing from postpartum day (PPD) 8 to PPD 35/36. In-life, clinical pathology, anatomic pathology, and toxicokinetics evaluations were performed.

High-quality triplicate electrocardiogram monitoring in a first-in-man study: potential for early detection of drug-induced QT prolongation.

Background: QT interval prolongation is associated with an increased risk of potentially fatal ventricular tachycardias, including torsade de pointes. Regulatory guidance recommends the "thorough QT/QTc" (TQT) study as the gold standard for assessing the propensity of novel nonantiarrhythmic drugs to delay cardiac repolarization. An opportunity exists, however, to use high-quality electrocardiogram (ECG) data from first-in-man trials as an exploratory and complementary approach to gain early insight into potential risk of QT prolongation.

Pharmacokinetics, safety profile, and efficacy of aliskiren in pediatric patients with hypertension.

Objective: To assess the pharmacokinetics (PK) and safety profile of aliskiren in pediatric patients (6-17 years old) with hypertension.

Methods: Patients were randomized to a single weight-based dose of either 2 mg/kg (n = 19) or 6 mg/kg (n = 20) of aliskiren daily for 8 days. The PK, pharmacodynamics, safety profile, and efficacy of aliskiren were assessed.

Pharmacokinetics and pharmacodynamics of aliskiren/hydrochlorothiazide single-pill combination tablets and free combination of aliskiren and hydrochlorothiazide.

Single-pill combinations (SPCs) of complementary antihypertensive agents provide patients with a simple and effective treatment regimen. To ensure that the efficacy and safety of an SPC is the same as that for the individual drugs administered together (free combination), SPC and free-combination formulations must be shown to be bioequivalent. Three open-label, randomized studies compared the pharmacokinetics of SPC tablets of the direct renin inhibitor aliskiren and hydrochlorothiazide (HCT), at doses of 150/25, 300/12.

Involvement of endogenous hydrogen sulfide in cigarette smoke-induced changes in airway responsiveness and inflammation of rat lung.

Hydrogen sulfide (H₂S), recently considered the third endogenous gaseous transmitter, may have an important role in systemic inflammation. We investigated whether endogenous H₂S may be a crucial mediator in airway responsiveness and airway inflammation in a rat model of chronic exposure to cigarette smoke (CS). Rats randomly divided into control and CS-exposed groups were treated with or without sodium hydrosulfide (NaHS, donor of H₂S) or propargylglycine (PPG, inhibitor of cystathionine-γ-lyase [CSE], an H₂S-synthesizing enzyme) for 4-month exposure.

Absence of a pharmacokinetic interaction between entecavir and adefovir.

This study evaluated the effect of entecavir on the pharmacokinetics of adefovir and the effect of adefovir on the pharmacokinetics of entecavir using a fixed-sequence crossover design in healthy adult subjects. Subjects received 10 mg of adefovir once daily on days 1 to 4, 1 mg of entecavir on days 5 to 14, and 1 mg of entecavir plus 10 mg of adefovir on days 15 to 24. Pharmacokinetic assessments were performed on days 4 and 24 for adefovir and on days 14 and 24 for entecavir.

Quantitative determination of BMS-378806 in human plasma and urine by high-performance liquid chromatography/tandem mass spectrometry.

BMS-378806 is a human immunodeficiency virus (HIV) entry inhibitor that is being developed for the oral treatment of HIV infection. Human plasma and urine LC/MS/ MS methods have been developed and validated for the quantitation of BMS-378806. For human plasma method, methyl t-butyl ether was used to extract BMS-378806 from plasma in a 96-well format, and the organic layers were dried down and then reconstituted for the injection, while a dilute-and-shoot approach was used for human urine method in a 96-well format.

Entecavir pharmacokinetics, safety, and tolerability after multiple ascending doses in healthy subjects.

A double-blind, placebo-controlled, multiple oral dose escalation study was conducted to investigate the pharmacokinetics, safety, and tolerability of entecavir in healthy subjects. Eight subjects were assigned to each of the 3 dose panels (0.1 mg, 0.

The effect of ravuconazole on the pharmacokinetics of nelfinavir in healthy male volunteers.

An open-label, nonrandomized study was conducted to assess the effect of ravuconazole on the pharmacokinetics of concomitantly administered nelfinavir. Healthy volunteers received 750 mg nelfinavir on day 1, 750 mg nelfinavir and 400 mg ravuconazole on day 2, 400 mg ravuconazole on days 3 to 28, and 750 mg nelfinavir and 400 mg ravuconazole on day 29. The geometric means of C(max) and area under the curve of nelfinavir coadministered with ravuconazole were 30.

The influence of renal function on hydroxyurea pharmacokinetics in adults with sickle cell disease.

This was an open-label, nonrandomized, 2-center study conducted to assess the influence of renal function on the pharmacokinetics of hydroxyurea in adults with sickle cell disease (SCD). Seventeen patients were divided into 5 groups: normal renal function (n = 7), mild renal impairment (n = 2), moderate renal impairment (n = 3), severe renal impairment (n = 2), and end-stage renal disease (ESRD, n = 3). Except for patients with ESRD, all the patients received a 15-mg/kg single oral dose of hydroxyurea.

Effect of food on the oral bioavailability of didanosine from encapsulated enteric-coated beads.

The objective of this study was to assess the effect of food and timing of meals on the bioavailability of didanosine from encapsulated enteric-coated beads. Four different independent, open-label, single-dose, randomized, crossover studies were conducted in healthy subjects (n = 20-30). Didanosine (400 mg) was given concomitantly with a high-fat meal, light meal, yogurt, and applesauce.