scholarly journals Phase 3 pharmacokinetics and safety study of a posaconazole tablet formulation in patients at risk for invasive fungal disease

2015 ◽  
Vol 71 (3) ◽  
pp. 718-726 ◽  
Author(s):  
Oliver A. Cornely ◽  
Rafael F. Duarte ◽  
Shariq Haider ◽  
Pranatharthi Chandrasekar ◽  
David Helfgott ◽  
...  
Keyword(s):  
At Risk ◽  
Steady State ◽  
Invasive Fungal Disease ◽  
Fungal Disease ◽  
Oral Suspension ◽  
Safety Study ◽  
Phase 3 ◽  
Once Daily ◽  
Patients At Risk ◽  
Phase 1B

This Phase 1B study showed that a single tablet of 300 mg of posaconazole, given once daily as prophylaxis to 210 patients at risk for invasive fungal disease, was as safe as that reported for posaconazole oral suspension and achieved steady-state >500 ng/mL for all but one patient.

scholarly journals Phase 3 pharmacokinetics and safety study of a posaconazole tablet formulation in patients at risk for invasive fungal disease

2016 ◽  
Vol 71 (6) ◽  
pp. 1747-1747 ◽  
Author(s):  
Oliver A. Cornely ◽  
Rafael F. Duarte ◽  
Shariq Haider ◽  
Pranatharthi Chandrasekar ◽  
David Helfgott ◽  
...  
Keyword(s):  
At Risk ◽  
Invasive Fungal Disease ◽  
Fungal Disease ◽  
Tablet Formulation ◽  
Safety Study ◽  
Phase 3 ◽  
Patients At Risk

scholarly journals Pharmacokinetics and safety results from the Phase 3 randomized, open-label, study of intravenous posaconazole in patients at risk of invasive fungal disease

2017 ◽  
Vol 72 (12) ◽  
pp. 3501-3501 ◽  
Author(s):  
Oliver A Cornely ◽  
Michael N Robertson ◽  
Shariq Haider ◽  
Andrew Grigg ◽  
Michelle Geddes ◽  
...  
Keyword(s):  
At Risk ◽  
Invasive Fungal Disease ◽  
Fungal Disease ◽  
Open Label ◽  
Phase 3 ◽  
Open Label Study ◽  
Label Study ◽  
Patients At Risk

scholarly journals Pharmacokinetics and safety results from the Phase 3 randomized, open-label, study of intravenous posaconazole in patients at risk of invasive fungal disease

2017 ◽  
Vol 72 (12) ◽  
pp. 3406-3413 ◽  
Author(s):  
Oliver A Cornely ◽  
Michael N Robertson ◽  
Shariq Haider ◽  
Andrew Grigg ◽  
Michelle Geddes ◽  
...  
Keyword(s):  
At Risk ◽  
Invasive Fungal Disease ◽  
Fungal Disease ◽  
Open Label ◽  
Phase 3 ◽  
Open Label Study ◽  
Label Study ◽  
Patients At Risk

scholarly journals Phase 1B Study of the Pharmacokinetics and Safety of Posaconazole Intravenous Solution in Patients at Risk for Invasive Fungal Disease

2014 ◽  
Vol 58 (7) ◽  
pp. 3610-3617 ◽  
Author(s):  
Johan Maertens ◽  
Oliver A. Cornely ◽  
Andrew J. Ullmann ◽  
Werner J. Heinz ◽  
Gopal Krishna ◽  
...  
Keyword(s):  
Steady State ◽  
Invasive Fungal Disease ◽  
Central Line ◽  
Fungal Disease ◽  
Average Concentration ◽  
Study Phase ◽  
Time Curve ◽  
Exposure Target ◽  
Patients At Risk ◽  
Phase 1B

ABSTRACTThis was a phase 1B, dose-ranging, multicenter, pharmacokinetics, and safety study of cyclodextrin-based posaconazole intravenous (i.v.) solution administered through a central line to subjects at high risk for invasive fungal disease (part 1 of a 2-part study [phase 1B/3]). Initially, the safety and tolerability of single-dose posaconazole i.v. 200 mg (n= 10) were compared with those of a placebo (n= 11). Subsequently, 2 doses were evaluated, posaconazole i.v. 200 mg once daily (q.d.) (n= 21) and 300 mg q.d. (n= 24). The subjects received twice-daily (b.i.d.) posaconazole i.v. on day 1, followed by 13 days of posaconazole i.v. q.d., then 14 days of posaconazole oral suspension 400 mg b.i.d. The steady-state (day 14) exposure target (average concentration [areas under concentration-time curve {AUCs}/24 h, average concentrations at steady state {Cavgs}], of ≥500 to ≤2,500 ng/ml in ≥90% of the subjects) was achieved by 94% of the subjects for 200 mg posaconazole q.d. and by 95% of subjects for 300 mg posaconazole q.d. The desired exposure target (mean steady-stateCavg, ∼1,200 ng/ml) was 1,180 ng/ml in the 200-mg dosing cohort and was exceeded in the 300-mg dosing cohort (1,430 ng/ml). Posaconazole i.v. was well tolerated. Posaconazole i.v. 300 mg q.d. was selected for the phase 3 study segment. (This study has been registered at ClinicalTrials.gov under registration no. NCT01075984.)

scholarly journals Pharmacokinetics and exposure–response analysis of venetoclax+obinutuzumab in chronic lymphocytic leukaemia: phase 1b study and phase 3 CLL14 trial

2021 ◽  
Author(s):  
Divya Samineni ◽  
Leonid Gibiansky ◽  
Bei Wang ◽  
Shweta Vadhavkar ◽  
Richa Rajwanshi ◽  
...  
Keyword(s):  
Steady State ◽  
Chronic Lymphocytic Leukaemia ◽  
Lymphocytic Leukaemia ◽  
Response Analysis ◽  
Parameter Estimates ◽  
Phase 3 ◽  
Once Daily ◽  
Exposure Response ◽  
Phase 1B ◽  
Grade 3

Aims: To investigate pharmacokinetics (PK) and exposure-response of the 400 mg once daily venetoclax dose regimen in combination with obinutuzumab in the phase 3 CLL14 study approved for the treatment of first-line (1L) chronic lymphocytic leukaemia (CLL). Methods: Parameter estimates and uncertainty estimated by a previously developed population PK (popPK) model were used as informative priors for this analysis. They were re-estimated, then used to evaluate additional covariate effects, describe venetoclax PK when administered with obinutuzumab, and provide empirical Bayes estimates of PK parameters and exposure. Exposure-progression-free survival (PFS) and exposure-safety relationships were assessed using CLL14 data, with steady-state exposure at the nominal target dose (C) as the predictor variable. Exposure-safety analyses were conducted using logistic regression for selected treatment-emergent grade ≥3 adverse events (AEs) and serious AEs (SAEs). Dose intensities were summarized by tertiles of C. Results: PK data from 274 patients (CLL14, n=194; phase 1b dose-finding study GP28331, n=80) were included. The final model provided good fit of observed data. Obinutuzumab co administration, history of prior treatments, and disease severity at baseline had no appreciable influence on venetoclax steady-state exposure. No significant correlations were observed between venetoclax exposure and PFS, or between venetoclax exposure and the probability of treatment-emergent grade ≥3 neutropenia, grade ≥3 thrombocytopenia, grade ≥3 infections and SAEs. Median dose intensities for venetoclax and obinutuzumab remained similar across venetoclax exposure tertiles. Conclusion: PopPK and exposure efficacy, -safety and -tolerability analyses support the 400 mg once-daily venetoclax dose plus obinutuzumab in patients with 1L CLL.

scholarly journals Lessons from an Educational Invasive Fungal Disease Conference on Hospital Antifungal Stewardship Practices across the UK and Ireland

2021 ◽  
Vol 7 (10) ◽  
pp. 801
Author(s):  
Alida Fe Talento ◽  
Malcolm Qualie ◽  
Laura Cottom ◽  
Matthijs Backx ◽  
P. Lewis White
Keyword(s):  
At Risk ◽  
Treatment Strategies ◽  
Invasive Fungal Disease ◽  
Fungal Disease ◽  
Diagnostic Tools ◽  
Optimal Time ◽  
Rapid Diagnostics ◽  
Antifungal Stewardship ◽  
Patients At Risk ◽  
The Uk

Invasive fungal disease (IFD) is a growing health burden. High mortality rates, increasing numbers of at-risk hosts, and a limited availability of rapid diagnostics and therapeutic options mean that patients are increasingly exposed to unnecessary antifungals. High rates of prescriptions promote patient exposure to undue toxicity and drive the emergence of resistance. Antifungal stewardship (AFS) aims to guide antifungal usage and reduce unnecessary exposure and antifungal consumption whilst maintaining or improving outcomes. Here, we examine several AFS approaches from hospitals across the UK and Ireland to demonstrate the benefits of AFS practices and support the broader implementation of AFS as both a necessary and achievable strategy. Since the accuracy and turnaround times (TATs) of diagnostic tools can impact treatment decisions, several AFS strategies have included the development and implementation of diagnostic-driven care pathways. AFS informed treatment strategies can help stratify patients on a risk basis ensuring the right patients receive antifungals at the optimal time. Using a multidisciplinary approach is also key due to the complexity of managing and treating patients at risk of IFD. Through knowledge sharing, such as The Gilead Antifungal Information Network (GAIN), we hope to drive practices that improve patient management and support the preservation of antifungals for future use.

Posaconazole oral suspension as salvage therapy for invasive fungal disease in patients with hematological diseases

2019 ◽  
Vol 14 (6) ◽  
pp. 477-488 ◽  
Author(s):  
Sudong Zhang ◽  
Ping Zhang ◽  
Zhao Wang ◽  
Li Liu ◽  
Yi He ◽  
...  
Keyword(s):  
Salvage Therapy ◽  
Invasive Fungal Disease ◽  
Fungal Disease ◽  
Oral Suspension ◽  
Hematological Diseases

scholarly journals 717. Lefamulin (LEF) vs. Moxifloxacin (MOX) in Patients With Community-Acquired Bacterial Pneumonia (CABP) at Risk for Poor Efficacy or Safety Outcomes: Pooled Subgroup Analyses From the Lefamulin Evaluation Against Pneumonia (LEAP) 1 and LEAP 2 Phase 3 Noninferiority Clinical Trials

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S322-S323
Author(s):  
Jennifer Schranz ◽  
Lisa Goldberg ◽  
Anita F Das ◽  
Elizabeth Alexander ◽  
Gregory J Moran ◽  
...  
Keyword(s):  
At Risk ◽  
Clinical Response ◽  
Study Drug ◽  
The United States ◽  
Chronic Obstructive ◽  
Phase 3 ◽  
Safety Concerns ◽  
Safety Outcomes ◽  
Patients At Risk ◽  
History Of

Abstract Background In the United States, CABP is the second most common cause of hospitalization and a leading cause of infectious death. Patients with chronic obstructive pulmonary disease (COPD)/asthma or diabetes are at risk for CABP and associated mortality. Similarly, patients with underlying cardiac or liver disease are at risk for potential cardiac or liver toxicities, respectively, associated with CABP antimicrobials, and patients aged ≥65 years are at risk for both efficacy/safety concerns. We report pooled efficacy/safety outcomes in at-risk subgroups from the LEAP 1 and 2 phase 3 trials. Methods In LEAP 1, patients with CABP (PORT III–V) received IV LEF 150 mg q12h for 5–7 days or MOX 400mg q24h for 7 days, with optional IV-to-oral switch (600 mg LEF q12h or 400 mg MOX q24h). In LEAP 2, patients with CABP (PORT II–IV) received oral LEF 600 mg q12h for 5 days or MOX 400 mg q24h for 7 days. Both studies assessed early clinical response (ECR; 96 ± 24 hours after first dose) in the intent-to-treat (ITT; all randomized patients) population (FDA primary endpoint) and investigator assessment of clinical response (IACR) at test-of-cure (TOC; 5–10 days after last dose) in the modified ITT (≥1 study drug dose) and clinically evaluable (met predefined evaluability criteria) populations (EMA coprimary endpoints). Pooled analyses used a 10% noninferiority margin. Safety was assessed in all randomized and treated patients. Results 1289 ITT patients were randomized to LEF (n = 646) or MOX (n = 643); of whom, 297 (23.0%) were aged 65–74 years and 220 (17.1%) were ≥75 years; 232 patients (18.0%) had COPD/asthma and 168 (13.0%) had diabetes mellitus (DM). At baseline, 501 patients (38.9%) had history of hypertension, 73 (5.7%) had history of arrhythmia, and 263 (20.4%) had transaminitis. The figure shows efficacy by age and in COPD/asthma and DM patients. Treatment-emergent adverse events, electrocardiogram assessments, and laboratory results in patients at risk for cardiac and hepatic safety concerns are shown in Tables 1 and 2. Conclusion In pooled analyses of LEAP 1 and 2, LEF efficacy was high and similar to MOX in patients at risk of efficacy concerns and LEF showed a safety profile similar to that of MOX in patients at risk of safety concerns. LEF is a promising new option for IV/oral monotherapy of CABP in patients at risk of poor outcomes due to CABP or to antimicrobial therapy for CABP. Disclosures All authors: No reported disclosures.

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