Pharmacokinetic interactions between simeprevir and ledipasvir in treatment naive hepatitis C virus genotype 1-Infected patients without cirrhosis treated with a simeprevir-sofosbuvir-ledipasvir regimen

Interactions between simeprevir (hepatitis C virus [HCV] NS3/4A protease inhibitor) and ledipasvir (HCV NS5A replication complex inhibitor) were investigated in treatment-naive HCV genotype 1-infected patients without cirrhosis, treated with simeprevir-sofosbuvir-ledipasvir in a two-panel, phase 2, open-label study. Patients had stable background treatment with sofosbuvir (400 mg once daily [QD]). In panel 1 (n = 20), the effect of ledipasvir (90 mg QD) on simeprevir (150 mg QD) was studied. Patients received simeprevir and sofosbuvir from days 1 to 14; steady-state pharmacokinetics (PK) of simeprevir was assessed (day 14). On day 15, ledipasvir was added and steady-state PK of simeprevir in the combination was evaluated (day 28). In panel 2 (n = 20), the effect of simeprevir on ledipasvir was investigated. From days 1 to 14, patients received ledipasvir and sofosbuvir and steady-state PK of ledipasvir was assessed (day 14). On day 15, simeprevir was added and a full PK profile was obtained (day 28). The least-squares mean maximum plasma concentration and area under the concentration-time curve (90% confidence interval) increased 2.3-fold (2.0- to 2.8-fold) and 3.1-fold (2.4- to 3.8-fold) for simeprevir, respectively (panel 1), and 1.6-fold (1.4- to 1.9-fold) and 1.7-fold (1.6- to 2.0-fold) for ledipasvir, respectively (panel 2), in the presence versus the absence of the other drug. All patients achieved sustained virologic responses 12 weeks after treatment end. Adverse events, mainly grade 1/2, occurred in 80% of patients; the most common was photosensitivity (45%). Due to the magnitude of interaction and the limited amount of safety data available, the use of this treatment combination is not recommended

Single- and multiple-dose pharmacokinetics and safety of pimodivir, a novel, non-nucleoside polymerase basic protein 2 subunit inhibitor of the influenza A virus polymerase complex, and interaction with oseltamivir: a Phase 1 open-label study in healthy volunteers

AIMS: The aim of this study was to evaluate the drug-drug interaction between pimodivir, a novel, non-nucleoside polymerase basic protein 2 (PB2) subunit inhibitor of the influenza A virus polymerase complex, and oseltamivir, to assess the feasibility of this combination therapy. Furthermore, single- and multiple-dose pharmacokinetics and safety of pimodivir in healthy volunteers were assessed. METHODS: In Part 1 of this open-label Phase 1 study, healthy volunteers (n = 18) were randomized to one of six cross-over treatment sequences, each comprising administration of oseltamivir 75 mg or pimodivir 600 mg or combination thereof twice daily on Days 1-4, followed by a single morning dose on Day 5. Between each treatment session, there was a minimum 5-day washout period. In Part 2, healthy volunteers (n = 16) randomly received pimodivir 600 mg or placebo (3:1) twice daily on Days 1-9, followed by a single morning dose on Day 10. Pharmacokinetics of pimodivir, oseltamivir and oseltamivir carboxylate, and safety were assessed. RESULTS: In Part 1, co-administration of pimodivir with oseltamivir increased the Cmax of pimodivir by 31% (90% CI: 0.92-1.85) with no change in Cmin or AUC12h . Pimodivir had no effect on oseltamivir or oseltamivir carboxylate pharmacokinetics. In Part 2, after single- and multiple-dose administration of pimodivir, there was a 1.2- and 1.8-fold increase in Cmax and AUC12h , respectively, between Day 1 and Day 10. The most frequently reported treatment-emergent adverse event was diarrhoea (n = 7 each in Part 1 and 2). CONCLUSION: Combination treatment with pimodivir and oseltamivir in healthy volunteers showed no clinically relevant drug-drug interactions. No safety concerns were identified with pimodivir 600 mg twice daily alone or in combination with oseltamivir 75 mg twice daily.status: publishe

Sample Management: Recommendation for best practices and harmonization from the Global Bioanalysis Consortium Harmonization Team

The regulations do not contain much guidance on sample management; however this is a very important aspect in regulatory work. A balanced team was formed to discuss the aspects involved and to put forward recommendations. Sampling conditions should be described in the protocol and in the laboratory manual. Items to be described include volume, anticoagulant, protection from light, labelling. The correct procedures for storing the samples at the clinical site and for shipment of the samples are also very important, along with the accompanying information. The chain of custody for the samples must be maintained throughout the complete lifespan of each sample. Therefore storage location and conditions must also be clearly defined at the analytical lab, pre and post analysis. A transparent way to do this is via a LIMS. The storage temperature of the samples must be traceable and controlled, via freezer monitoring. The team suggests to move away from using temperatures to define the storage condition, but rather move to a standard convention of room temperature, refrigerator, freezer and ultra-freeze

Pharmacokinetics, Antiviral Activity, and Safety of Rilpivirine in Pregnant Women with HIV-1 Infection: Results of a Phase 3b, Multicenter, Open-Label Study

<p>Article full text</p> <p>The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s40121-017-0184-8"><b>here</b>.</a></p> <p>Provide enhanced content for this article</p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p>Other enhanced features include, but are not limited to:</p> <ul> <li>Slide decks</li> <li>Videos and animations</li> <li>Audio abstracts</li> <li>Audio slides</li> </ul