Real-world use of avatrombopag in patients with chronic liver disease and thrombocytopenia undergoing a procedure.

The phase 4 observational cohort study assessed the effectiveness and safety of the thrombopoietin receptor agonist avatrombopag in patients with chronic liver disease (CLD) and thrombocytopenia undergoing a procedure. Patients with CLD may have thrombocytopenia, increasing the risk of periprocedural bleeding. Prophylactic platelet transfusions used to reduce this risk have limitations including lack of efficacy and transfusion-associated reactions.

Avatrombopag ethnic sensitivity analysis in chronic liver disease and thrombocytopenia patients: individual-level pooled analysis.

Introduction: Few data have been published on the ethnic sensitivity of effectiveness, pharmacokinetics (PK), and pharmacodynamics (PD) of avatrombopag for the management of thrombocytopenia in patients with chronic liver disease (CLD).

Methods: An ethnic sensitivity analysis was performed based on the results from two phase III studies (ADAPT-1 and ADAPT-2), with a primary endpoint of the proportion of patients without the requirement of platelet transfusion or rescue treatment for bleeding after randomization to 7 days following a scheduled procedure, and three phase I studies in healthy subjects. Cochran-Mantel-Haenszel and Fisher's exact tests were used to compare the differences in effectiveness in different ethnicities and overall population.

Avatrombopag for chemotherapy-induced thrombocytopenia in patients with non-haematological malignancies: an international, randomised, double-blind, placebo-controlled, phase 3 trial.

Background: Chemotherapy-induced thrombocytopenia is common and causes chemotherapy dose reductions or treatment delays, bleeding, and suboptimal oncological outcomes. We aimed to evaluate avatrombopag, a thrombopoietin receptor agonist that increases platelet counts, in patients with non-haematological cancer and platelet counts lower than 50 ×10 cells per L.

Methods: In this randomised, double-blind, placebo-controlled, phase 3 study, patients aged 18 years or older at 71 hospitals or cancer treatment centres in China, Hungary, Poland, Russia, Serbia, Ukraine, and the USA and with ovarian, bladder, or lung cancer receiving chemotherapy who had severe thrombocytopenia were randomly assigned (2:1) to oral avatrombopag 60 mg or oral placebo once daily given 5 days before and after chemotherapy, with randomisation stratified by number of chemotherapy drugs used.

Phase 3 randomised study of avatrombopag, a novel thrombopoietin receptor agonist for the treatment of chronic immune thrombocytopenia.

Avatrombopag, an oral thrombopoietin receptor agonist, was compared with placebo in a 6-month, multicentre, randomised, double-blind, parallel-group Phase 3 study, with an open-label extension phase, to assess the efficacy and safety of avatrombopag (20 mg/day) in adults with chronic immune thrombocytopenia (ITP) and a platelet count <30 × 10 /l (ClinicalTrials.gov identifier NCT01438840). The primary endpoint was the cumulative number of weeks of platelet response (platelet count ≥50 × 10 /l) without rescue therapy for bleeding; secondary endpoints included platelet response rate at day 8 and reductions in the use of concomitant medications.

Metabolism, Excretion, and Mass Balance of Solithromycin in Humans.

Solithromycin, a novel macrolide and the first fluoroketolide, is being developed as a therapy for community-acquired bacterial pneumonia, with a distinct mechanism that provides activity against macrolide-resistant bacteria. The pharmacokinetics, metabolism, and excretion of solithromycin were studied in healthy male subjects after oral administration of a single 800-mg (∼100-μCi) dose of [C]solithromycin. Solithromycin was well tolerated, and absorption from the solution occurred with a median time to peak concentration of 4.

Development of an Adult Physiologically Based Pharmacokinetic Model of Solithromycin in Plasma and Epithelial Lining Fluid.

Solithromycin is a fluoroketolide antibiotic under investigation for community-acquired bacterial pneumonia (CABP). We developed a whole-body physiologically based pharmacokinetic (PBPK) model for solithromycin in adults using PK-Sim and MoBi version 6.2, which incorporated time-dependent CYP3A4 auto-inhibition.

Solithromycin, a novel macrolide, does not prolong cardiac repolarization: a randomized, three-way crossover study in healthy subjects.

Background: Macrolide antibiotics may cause QT prolongation.

Objectives: To study the QT effect of a novel macrolide, solithromycin.

Methods: This was a thorough QT study with a three-way crossover design performed in healthy male and female subjects to evaluate the ECG effects of a novel macrolide, solithromycin.

SOLITAIRE-IV: A Randomized, Double-Blind, Multicenter Study Comparing the Efficacy and Safety of Intravenous-to-Oral Solithromycin to Intravenous-to-Oral Moxifloxacin for Treatment of Community-Acquired Bacterial Pneumonia.

Background: Solithromycin, a novel macrolide antibiotic with both intravenous and oral formulations dosed once daily, has completed 2 global phase 3 trials for treatment of community-acquired bacterial pneumonia.

Methods: A total of 863 adults with community-acquired bacterial pneumonia (Pneumonia Outcomes Research Team [PORT] class II-IV) were randomized 1:1 to receive either intravenous-to-oral solithromycin or moxifloxacin for 7 once-daily doses. All patients received 400 mg intravenously on day 1 and were permitted to switch to oral dosing when clinically indicated.

A Phase 2 Trial of Oral Solithromycin 1200 mg or 1000 mg as Single-Dose Oral Therapy for Uncomplicated Gonorrhea.

Background: Progressive resistance to antimicrobial agents has reduced options for gonorrhea therapy worldwide. Solithromycin (CEM-101) is a novel oral fluoroketolide antimicrobial with substantial in vitro activity against Neisseria gonorrhoeae.

Methods: We conducted a phase 2 trial of 2 oral doses of solithromycin (1200 and 1000 mg) for treatment of uncomplicated gonorrhea.

Safety and Pharmacokinetics of Solithromycin in Subjects with Hepatic Impairment.

Solithromycin, a new macrolide and the first fluoroketolide, is in late-stage clinical development and, like older macrolides, is primarily metabolized and excreted through liver-dependent mechanisms. This study evaluated the safety and pharmacokinetics of solithromycin in patients with chronic liver disease. This open-label, multiple-dose study in subjects with hepatic impairment and in healthy control subjects (matched for age, weight, and sex) enrolled 8 Child-Pugh class A (mild), 8 class B (moderate), and 8 class C (severe) patients and 9 healthy controls.

Randomized, double-blind, multicenter phase 2 study comparing the efficacy and safety of oral solithromycin (CEM-101) to those of oral levofloxacin in the treatment of patients with community-acquired bacterial pneumonia.

Solithromycin, a new macrolide, and the first fluoroketolide in clinical development, with activity against macrolide-resistant bacteria, was tested in 132 patients with moderate to moderately severe community-acquired bacterial pneumonia (CABP) in a multicenter, double-blind, randomized phase 2 study. Patients were enrolled and randomized (1:1) to either 800 mg solithromycin orally (PO) on day 1, followed by 400 mg PO daily on days 2 to 5, or 750 mg levofloxacin PO daily on days 1 to 5. Efficacy outcome rates of clinical success at the test-of-cure visit 4 to 11 days after the last dose of study drug were comparable in the intent-to-treat (ITT) (84.

Thoracic and lumbar paravertebral blocks for outpatient lithotripsy.

Paravertebral nerve block has been used for a variety of surgical procedures to provide unilateral anesthesia and postoperative analgesia. We report the successful application of this regional anesthesia modality for outpatient lithotripsy. Preoperatively, thoracic and lumbar paravertebral nerve blocks with 0.