A randomized, placebo-controlled pilot study of upamostat, a host-directed serine protease inhibitor, for outpatient treatment of COVID-19.

Objectives: We performed a pilot study of upamostat, a serine protease inhibitor, in outpatients with symptomatic COVID-19 before a pivotal trial.

Methods: SARS-CoV-2 patients with ≥2 moderate-severe symptoms onset within 5 days were randomized to oral upamostat 200 or 400 mg or placebo daily for 14 days. Patients completed COVID-19 symptom questionnaires daily for 28 days, then thrice weekly for 4 weeks, and underwent physical and laboratory examinations periodically.

Phase I study of opaganib, an oral sphingosine kinase 2-specific inhibitor, in relapsed and/or refractory multiple myeloma.

Multiple myeloma (MM) remains an incurable disease and there is an unmet medical need for novel therapeutic drugs that do not share similar mechanisms of action with currently available agents. Sphingosine kinase 2 (SK2) is an innovative molecular target for anticancer therapy. We previously reported that treatment with SK2 inhibitor opaganib inhibited myeloma tumor growth in vitro and in vivo in a mouse xenograft model.

Recent Progress in the Development of Opaganib for the Treatment of Covid-19.

The Covid-19 pandemic driven by the SARS-CoV-2 virus continues to exert extensive humanitarian and economic stress across the world. Although antivirals active against mild disease have been identified recently, new drugs to treat moderate and severe Covid-19 patients are needed. Sphingolipids regulate key pathologic processes, including viral proliferation and pathologic host inflammation.

Bimodal Release Ondansetron Improves Stool Consistency and Symptomatology in Diarrhea-Predominant Irritable Bowel Syndrome: A Randomized, Double-Blind, Trial.

Introduction: Previous, small studies have suggested that ondansetron has beneficial effects in diarrhea-predominant irritable bowel syndrome (IBS-D). This randomized, double-blind study evaluated the efficacy and safety of daily 12 mg RHB-102, an investigational bimodal release ondansetron tablet, in IBS-D.

Methods: Men and women with IBS-D by the Rome III criteria, Bristol Stool Scale ≥6 on 2 or more days weekly, and average daily worst pain intensity ≥3/10 were randomized 60:40 to RHB-102 or placebo once daily for 8 weeks.

Absence of QT prolongation after administration of a 24-mg bimodal-release ondansetron pill (RHB-102).

Objectives: Prospective data evaluating the effect of ondansetron on the corrected QT (QTc) interval is lacking in emergency department clinical use. As part of a randomized trial of a 24-mg bimodal-release ondansetron (RHB-102) pill, we tested the effect of RHB-102 compared to placebo on QTc change.

Methods: This was a planned safety outcome analysis within a multicenter, double-blind, placebo-controlled trial.

Bimodal Release Ondansetron for Acute Gastroenteritis Among Adolescents and Adults: A Randomized Clinical Trial.

Importance: Vomiting resulting from acute gastroenteritis is commonly treated with intravenous antiemetics in acute care settings. If oral treatment were beneficial, patients might not need intravenous administered hydration or medication. Furthermore, a long-acting treatment could provide sustained relief from nausea and vomiting.

A randomised placebo-controlled multicentre trial of intravenous semapimod HCl for moderate to severe Crohn's disease.

Objective: Semapimod, a small molecule known to inhibit proinflammatory cytokine activity, was studied to determine the optimal dose necessary to achieve a response in patients with moderate to severe Crohn's disease (CD).

Methods: A randomised, double-blind, placebo-controlled trial (CD04) was carried out followed by an open-label extension study (CD05). The trial was conducted in international multicentre outpatient clinics and included patients with moderate to severe CD (Crohn's Disease Activity Index (CDAI) 250-400).

Pharmacokinetics of a controlled-release misoprostol vaginal insert at term.

Objective: The objective of this investigation was to report the pharmacokinetic properties of misoprostol administered intravaginally to women at term via a controlled-release hydrogel polymer insert.

Methods: This open-label, dose escalation trial consisted of 31 nulliparous women at term who were treated intravaginally in cohorts of six with inserts containing reservoirs from 25 through 300 microg (7 at 200 microg) of misoprostol. Inserts remained intravaginally until the patient went into labor, developed adverse events, or completed 24 hours of treatment.

Misoprostol dose selection in a controlled-release vaginal insert for induction of labor in nulliparous women.

Objective: The purpose of this study was to identify the maximum tolerable dose and to determine the efficacy of different misoprostol dose reservoirs in an intravaginal controlled-release hydrogel polymer.

Study Design: Nulliparous women at > or = 37 weeks' gestation requiring cervical ripening and induction of labor were treated with misoprostol in a controlled-release, retrievable hydrogel polymer vaginal insert. Sequential cohorts of 6 patients were to be treated with escalating dose reservoirs of 25, 50, 100, 200, and 300 mug.

Macrophage inhibitor, semapimod, reduces tumor necrosis factor-alpha in myocardium in a rat model of ischemic heart failure.

Pharmaceutical agents aimed at reducing tumor necrosis factor-alpha (TNF-alpha) levels appeared to be attractive possibilities in the medical management of heart failure, as heart failure was shown to be associated with high TNF-alpha levels. However, therapies specifically targeting TNF-alpha failed to show any survival benefit. We examined whether a broad inhibition of inflammatory cytokine production secondary to macrophage inhibition would be more effective at improving cardiac function in the setting of heart failure.

A randomized trial of docosahexaenoic acid supplementation during the third trimester of pregnancy.

Objective: To hypothesize that higher intake of docosahexaenoic acid, an n-3 long chain polyunsaturated fatty acid, would increase duration of gestation and birth weight in US women.

Methods: This was a randomized, double-blind, controlled, clinical trial. Subjects were enrolled in an ambulatory clinic where they received prenatal care.

Inhibition of stress-activated MAP kinases induces clinical improvement in moderate to severe Crohn's disease.

Background & Aims: We investigated if inhibition of mitogen-activated protein kinases (MAPKs) was beneficial in Crohn's disease.

Methods: Inhibition of JNK and p38 MAPK activation with CNI-1493, a guanylhydrazone, was tested in vitro. Twelve patients with severe Crohn's disease (mean baseline, CDAI 380) were randomly assigned to receive either 8 or 25 mg/m(2) CNI-1493 daily for 12 days.