No QTc Prolongation With Zanubrutinib: Results of Concentration-QTc Analysis From a Thorough QT Study in Healthy Subjects.

This thorough QT (TQT) study evaluated the effect of zanubrutinib on electrocardiogram (ECG) parameters by using concentration-QTc (C-QTc) analysis as the primary analysis for this study. Part A of the study determined the safety and tolerability of a single supratherapeutic dose of zanubrutinib (480 mg) in healthy volunteers. Part B was a randomized, blinded, placebo-controlled and positive-controlled, four-way crossover, TQT study of single therapeutic (160 mg) and supratherapeutic (480 mg) doses of zanubrutinib, placebo, and open-label moxifloxacin 400 mg.

Clinical Pharmacokinetics and Drug-Drug Interaction Potential for Coadministered SCY-078, an Oral Fungicidal Glucan Synthase Inhibitor, and Tacrolimus.

SCY-078 is an orally bioavailable triterpenoid glucan synthase inhibitor in clinical development as an intravenous and oral treatment of fungal infections caused by Candida and Aspergillus species. This was a sequential, single-center, open-label phase 1 study to assess the drug-drug interaction potential between SCY-078 and tacrolimus during concomitant administration in healthy subjects. In cohort 1, period 1, subjects received a single oral dose of tacrolimus 2 mg in the fasted state.

Lack of Impact by SCY-078, a First-in-Class Oral Fungicidal Glucan Synthase Inhibitor, on the Pharmacokinetics of Rosiglitazone, a Substrate for CYP450 2C8, Supports the Low Risk for Clinically Relevant Metabolic Drug-Drug Interactions.

SCY-078, the first in a new class of β 1,3-glucan synthesis inhibitors, is being developed as an oral and intravenous antifungal treatment for Candida and Aspergillus species fungal infections. In vitro, studies indicated SCY-078 is an inhibitor of cytochrome P450 (CYP) 2C8 with markedly lower effect over other CYP isozymes. To examine clinically relevant effects of the potential interaction with SCY-078, this phase 1, open-label, 2-period crossover study evaluated the pharmacokinetic parameters of rosiglitazone, a sensitive substrate of CYP2C8 metabolism, in the absence and presence of SCY-078 dosed to therapeutically relevant SCY-078 concentration exposure after repeat dosing.

Pharmacokinetics, pharmacodynamics, and metabolism of triethylenetetramine in healthy human participants: an open-label trial.

The selective Cu(II)-chelator, triethylenetetramine (TETA), is undergoing clinical trials for the treatment of heart failure in patients with diabetes. Recently, the authors showed that 2 acetylated metabolites, N(1)-acetyltriethylenetetramine (MAT) and N(1),N(10)-diacetyltriethylenetetramine (DAT), are formed in humans following oral TETA administration. Thus, it became necessary to determine whether the N-acetyltransferase (NAT) 2 phenotype has any effects on the pharmacological properties and safety profile of TETA.

Multicenter, double-blind, randomized comparison of wood creosote, the principal active ingredient of Seirogan, an herbal antidiarrheal medication, and loperamide in adults with acute nonspecific diarrhea.

Background: Seirogan, an herbal medication containing wood creosote, a mixture of simple phenolic (single-ring)compounds, has been marketed in Asia for the past century as an antidiarrheal and antispasmodic medication. This was the first randomized, double-blind study of this herbal medication in patients with acute, nonspecific diarrhea.

Objective: The aim of this study was to compare the efficacy and tolerability of wood creosote with those of loperamide hydrochloride in patients with acute, nonspecific diarrhea.

Wood creosote, the principal active ingredient of seirogan, an herbal antidiarrheal medicine: a single-dose, dose-escalation safety and pharmacokinetic study.

Study Objective: To assess the safety, tolerability and pharmacokinetics of escalating single doses of wood creosote, an herbal antidiarrheal and antispasmodic agent.

Design: Randomized, double-blind, placebo-controlled study.

Setting: Clinical research center.

Multiple-dose escalation, safety, and tolerability study of wood creosote, the principal active ingredient of seirogan, an herbal antidiarrheal medication, in healthy subjects.

Seirogan, an herbal medicine containing wood creosote (CAS 8021-39-4), a mixture of simple phenolic compounds, has been marketed for the past century in Asia for the treatment of acute diarrhea and associated symptoms, such as abdominal discomfort and cramping. The present study was designed to assess the safety and tolerability of an anticipated acute antidiarrheal dosing regimen. Sixty healthy males were randomized into five groups of 12 subjects each (9 wood creosote; 3 placebo) to receive 45-, 90-, 135-, 180-, and 225-mg tablets every 2 hours for five doses.

A Comparison of the Cough Profile of Fosinopril and Enalapril in Hypertensive Patients with a History of ACE Inhibitor-Associated Cough.

OBJECTIVE: Cough frequency and severity with fosinopril and enalapril were assessed in hypertensive patients with previous angiotensin-converting enzyme inhibitor (ACEI)-associated cough. DESIGN: Prospective, multicenter, randomized, 8-week double-blind treatment. PATIENTS: One hundred seventy-nine patients (mild-to-moderate hypertension, nonsmokers, mean age 58 years; 55% females; 72% Caucasian, 6% black, 19% Hispanic) were studied.