Dataset Information

Safety and pharmacokinetics of intravenous zanamivir treatment in hospitalized adults with influenza: an open-label, multicenter, single-arm, phase II study.

ABSTRACT: Intravenous zanamivir is a neuraminidase inhibitor suitable for treatment of hospitalized patients with severe influenza.Patients were treated with intravenous zanamivir 600 mg twice daily, adjusted for renal impairment, for up to 10 days. Primary outcomes included adverse events (AEs), and clinical/laboratory parameters. Pharmacokinetics, viral load, and disease course were also assessed.One hundred thirty patients received intravenous zanamivir (median, 5 days; range, 1-11) a median of 4.5 days (range, 1-7) after onset of influenza; 83% required intensive care. The most common influenza type/subtype was A/H1N1pdm09 (71%). AEs and serious AEs were reported in 85% and 34% of patients, respectively; serious AEs included bacterial pulmonary infections (8%), respiratory failure (7%), sepsis or septic shock (5%), and cardiogenic shock (5%). No drug-related trends in safety parameters were identified. Protocol-defined liver events were observed in 13% of patients. The 14- and 28-day all-cause mortality rates were 13% and 17%. No fatalities were considered zanamivir related. Pharmacokinetic data showed dose adjustments for renal impairment yielded similar zanamivir exposures. Ninety-three patients, positive at baseline for influenza by quantitative polymerase chain reaction, showed a median decrease in viral load of 1.42 log10 copies/mL after 2 days of treatment.Safety, pharmacokinetic and clinical outcome data support further investigation of intravenous zanamivir.NCT01014988.

SUBMITTER: Marty FM

PROVIDER: S-EPMC4047294 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Safety and pharmacokinetics of intravenous zanamivir treatment in hospitalized adults with influenza: an open-label, multicenter, single-arm, phase II study.

Marty Francisco M FM Man Choy Y CY van der Horst Charles C Francois Bruno B Garot Denis D Mánez Rafael R Thamlikitkul Visanu V Lorente José A JA Alvarez-Lerma Francisco F Brealey David D Zhao Henry H HH Weller Steve S Yates Phillip J PJ Peppercorn Amanda F AF

The Journal of infectious diseases 20130827 4

<h4>Background</h4>Intravenous zanamivir is a neuraminidase inhibitor suitable for treatment of hospitalized patients with severe influenza.<h4>Methods</h4>Patients were treated with intravenous zanamivir 600 mg twice daily, adjusted for renal impairment, for up to 10 days. Primary outcomes included adverse events (AEs), and clinical/laboratory parameters. Pharmacokinetics, viral load, and disease course were also assessed.<h4>Results</h4>One hundred thirty patients received intravenous zanamivi ...[more]

PMID: 23983212

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Project description:BackgroundOral antipyretics are commonly used to treat pediatric patients who develop fevers. However, patients presenting to the emergency department or undergoing surgery are frequently unable to tolerate oral antipyretics. Rectal formulations are available; however, this route of administration is unpredictable. The main objectives of this randomized controlled study was to evaluate the efficacy and safety of single or multiple doses of intravenous ibuprofen to acetaminophen (oral or suppository) in pediatric patients with fever and to assess plasma ibuprofen concentrations.MethodsThis multi-center study was conducted in hospitalized patients, ≤ 16 years, with a new onset of fever ≥ 38.3°C. Patients were randomly assigned to receive either 10 mg/kg intravenous ibuprofen or acetaminophen. Study drug was administered at hour 0, and thereafter every 4 h as needed, up to 5 days. The primary outcome was to evaluate the effect of a single dose of intravenous ibuprofen compared to acetaminophen in reducing temperature in the first 2 h after administration. Data were compared using an analysis of variance model for continuous measurements and Cochran-Mantel-Haenszel test of general association for categorical data. A two-sided testing was used and a p-value ≤ 0.05 was considered significant.ResultsA total of 103 patients received study medication. Intravenous ibuprofen resulted in a greater reduction in temperature as measured by the area under the change from baseline at 2 h (p = 0.005) and 4 h (<0.001); in a greater reduction in change from baseline temperature compared to treatment with acetaminophen, and it reduced fever throughout a 24 h dosing period. There were no differences in safety parameters or serious adverse events.ConclusionsA single 10 mg/kg dose of intravenous ibuprofen provided a significant reduction of temperature for febrile pediatric patients compared to those that received 10 mg/kg acetaminophen at 2 h and 4 h post-treatment. A reduction in temperature was also demonstrated over 24 h; however the reduction was not considered statically significant. Intravenous ibuprofen provides an effective option for reducing fever in hospitalized pediatric patients.Trial registrationThe study was registered on ClinicalTrials.gov on 26 October 2009, Study Identifier: NCT01002573.

Project description:ObjectiveTo evaluate the pharmacokinetics, safety, and tolerability of brivaracetam (BRV) as 15-min intravenous (IV) infusion and bolus (≤2-min injection).MethodsEP0065 (ClinicalTrials.gov: NCT03405714) was a Phase 2, multicenter, open-label trial in patients ≥1 month to <16 years of age with epilepsy. Patients received up to 5 mg/kg/day BRV (not exceeding 200 mg/day). Enrollment was sequential by descending age, depending on safety review. Outcomes included BRV plasma concentrations before and after IV administration, treatment-emergent adverse events (TEAEs), and discontinuations due to TEAEs.ResultsFifty patients were enrolled, received BRV, and completed the trial. Twenty-six patients (52.0%) received 15-min infusions and 24 (48.0%) received bolus injections. Most patients (80.0%) received one IV dose. In the 15-min infusion group, geometric mean (GeoMean) BRV concentrations 15 (±2) min (n = 21) and 3 h (±15 min) (n = 21) post dose were 1903.0 ng/mL (geometric coefficient of variation [GeoCV]: 60.7%) and 1130.3 ng/mL (58.8%), respectively. In the bolus group, GeoMean BRV concentrations 15 (±2) min (n = 19) and 3 h (±15 min) (n = 21) post dose were 1704.8 ng/mL (GeoCV: 74.5%) and 1383.9 ng/mL (85.0%), respectively. Overall, 14 patients (28.0%) had TEAEs (15-min infusion: 8 [30.8%]; bolus: 6 [25.0%]), most commonly (≥5% of patients) somnolence (3 [6.0%]). Ten patients (20.0%) had drug-related TEAEs (15-min infusion: 6 [23.1%]; bolus: 4 [16.7%]). No patients discontinued due to TEAEs, and no deaths occurred.SignificanceIV BRV (up to 200 mg/day) was well tolerated in patients ≥1 month to <16 years of age, regardless of whether BRV was administered as 15-min infusion or bolus. No unexpected safety or pharmacokinetic differences were observed between patients receiving 15-min infusions or bolus, and plasma concentrations were in the expected range. Safety results were consistent with the known safety profile of oral BRV, with no new safety concerns identified.

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Project description:IntroductionKnee osteoarthritis (OA) is a common painful disorder. Intra-articular (IA) corticosteroid injections are frequently prescribed to treat knee pain. Lorecivivint (LOR), a novel IA cdc2-Like Kinase (CLK)/Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase (DYRK) inhibitor thought to modulate Wnt and inflammatory pathways, has appeared safe and demonstrated improved patient-reported outcomes compared with placebo. While LOR is proposed for stand-alone use, in clinical practice, providers might administer LOR in close time proximity to IA corticosteroid. This open-label, parallel-arm, healthy volunteer study assessed potential short-term safety, tolerability and pharmacokinetic (PK) interactions between IA LOR and triamcinolone acetonide (TCA) administered 7 days apart.MethodsHealthy volunteers were randomized to Treatment Sequence 1 (IA 40 mg TCA followed by IA 0.07 mg LOR) or Treatment Sequence 2 (IA 0.07 mg LOR followed by IA 40 mg TCA). Treatment-emergent adverse events (TEAEs) were categorized by "epoch", with epoch 1 spanning from first until second injection, and epoch 2 spanning from second injection until end of study. Plasma PK was assessed pre injection and out to 22 days after to assess PK treatment interaction.ResultsA total of 18 TEAEs were reported by 11 (27.5%) of 40 enrolled participants, and there were no serious adverse events. Thirteen TEAEs were reported in Treatment Sequence 1 and five in Treatment Sequence 2, similarly distributed between epochs 1 and 2. In all participants and at all time points, plasma LOR concentrations were below the limit of quantification (0.100 ng/mL). Geometric mean concentrations and PK parameters for TCA were similar between treatment sequences.ConclusionNo safety signals were observed. There were no quantifiable plasma concentrations of LOR in either Treatment Sequence. The PK of TCA was unaffected by previous LOR injection. These results suggest that IA administration of LOR and TCA in close time proximity is unlikely to pose a safety concern.Trial registrationClinicalTrials.gov identifier, NCT04598542.

Dataset Information

Safety and pharmacokinetics of intravenous zanamivir treatment in hospitalized adults with influenza: an open-label, multicenter, single-arm, phase II study.

Publications

Safety and pharmacokinetics of intravenous zanamivir treatment in hospitalized adults with influenza: an open-label, multicenter, single-arm, phase II study.

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