JNJ-73763989 is comprised of 2 short interfering RNAs (siRNAs), JNJ-73763976 and JNJ-73763924, that target hepatitis B virus (HBV) mRNAs for degradation, thereby inhibiting HBV replication. JNJ-56136379 is a capsid assembly modulator that inhibits HBV replication by inducing the formation of empty capsids (CAM-E). In 2 phase 1, open-label, non-randomized, single-center studies, the single-dose pharmacokinetics, safety, and tolerability of JNJ-73763989 or JNJ-56136379 were assessed in participants with moderate hepatic impairment (Child-Pugh Class B) versus participants with normal liver function.
View Article and Find Full Text PDFThe capsid assembly modulator JNJ-56136379 (bersacapavir) disrupts hepatitis B virus replication. It is metabolized via cytochrome P450 (CYP) 3A, but little is known about the drug-drug interactions of JNJ-56136379 when combined with drugs that inhibit or are metabolized by CYP3A. In a phase 1, open-label trial (NCT03945539), healthy adults received 1 dose of JNJ-56136379 with and without 21 days of prior exposure to itraconazole 200 mg (CYP3A inhibitor).
View Article and Find Full Text PDFBackground: JNJ-73763989 comprises two hepatitis B virus (HBV)-specific, liver-targeted N-galactosamine-conjugated short interfering RNA triggers, JNJ-73763976 and JNJ-73763924. JNJ-73763989 pharmacokinetics, safety and tolerability were assessed in two phase 1 studies: Japanese (NCT04002752), and non-Japanese healthy participants and chronic hepatitis B (CHB) patients also receiving the HBV capsid assembly modulator JNJ-56136379 and a nucleos(t)ide analogue (NA) (NCT03365947).
Methods: Healthy participant cohorts were double-blind and randomized to receive a single subcutaneous JNJ-73763989 dose (non-Japanese participants, 35, 100, 200, 300 or 400 mg; Japanese participants, 25, 100 or 200 mg) or placebo.
Capillary microsampling of 15 μl whole blood from fingersticks or heelsticks was used to collect pharmacokinetic (PK) samples from pediatric subjects in two projects. In a mebendazole multisite study in Ethiopia and Rwanda in subjects between 1 and 16 years old, complete PK profiles (7 timepoints) could be obtained, although some of the fingerstick samples were contaminated by the dosing formulation. In a multisite study with a respiratory syncytial virus drug in children between 1 and 24 months old, sparse PK sampling was done (2 samples).
View Article and Find Full Text PDFCancer Chemother Pharmacol
October 2019
Purpose: To characterize the trabectedin population pharmacokinetics in children and adolescent patients with cancer and compare it with the trabectedin pharmacokinetics in adults.
Methods: Plasma concentrations from ten adolescent and three children with cancer (age range 4.0-17.
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.
Introduction: Physiologic changes during pregnancy may impact the pharmacokinetics of drugs. In addition, efficacy and safety/tolerability concerns have been identified for some antiretroviral agents.
Methods: Human immunodeficiency virus (HIV)-1-infected pregnant women (18-26 weeks gestation) receiving the non-nucleoside reverse transcriptase inhibitor rilpivirine 25 mg once daily were enrolled in this phase 3b, open-label study examining the impact of pregnancy on the pharmacokinetics of rilpivirine when it is given in combination with other antiretroviral agents.
Antimicrob Agents Chemother
December 2017
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 ( = 20), the effect of ledipasvir (90 mg QD) on simeprevir (150 mg QD) was studied.
View Article and Find Full Text PDFJ Acquir Immune Defic Syndr
November 2016
Background: Treatment of HIV-1-infected women during pregnancy protects maternal health and reduces the risk of perinatal transmission of HIV-1. However, physiologic changes that occur during pregnancy may affect drug pharmacokinetics. This phase IIIb, open-label study evaluated the effects of pregnancy on the pharmacokinetics of the nonnucleoside reverse transcriptase inhibitor etravirine.
View Article and Find Full Text PDFThis study investigates 3 amorphous technologies to improve the dissolution rate and oral bioavailability of flubendazole (FLU). The selected approaches are (1) a standard spray-dried dispersion with hydroxypropylmethylcellulose (HPMC) E5 or polyvinylpyrrolidone-vinyl acetate 64, both with Vitamin E d-α-tocopheryl polyethylene glycol succinate; (2) a modified process spray-dried dispersion (MPSDD) with either HPMC E3 or hydroxypropylmethylcellulose acetate succinate (HPMCAS-M); and (3) confining FLU in ordered mesoporous silica (OMS). The physicochemical stability and in vitro release of optimized formulations were evaluated following 2 weeks of open conditions at 25°C/60% relative humidity (RH) and 40°C/75% RH.
View Article and Find Full Text PDFThe importance of appropriate sample management in regulated bioanalysis is undeniable for clinical and non-clinical study support due to the fact that if the samples are compromised at any stage prior to analysis, the study results may be affected. Health authority regulations do not contain specific guidance on sample management; therefore, as part of the Global Bioanalysis Consortium (GBC), the A5 team was established to discuss sample management requirements and to put forward recommendations. The recommendations from the team concern the entire life span of the sample and include the following: 1.
View Article and Find Full Text PDFJ Chromatogr B Analyt Technol Biomed Life Sci
February 2015
Tapentadol is a novel, centrally acting analgesic with 2 mechanisms of action, MOR agonism and noradrenaline (NA) reuptake inhibition in a single molecule. It is the first member of a new therapeutic class, MOR-NRI. A high throughput liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay was developed and validated for the quantitative analysis of tapentadol and its O-glucuronide metabolite in human serum.
View Article and Find Full Text PDFUnlabelled: Once-daily darunavir/ritonavir (800/100 mg), plus other antiretrovirals, is recommended for HIV-1-infected patients. Low therapy adherence is linked with poor outcomes. Pill burden can impact adherence.
View Article and Find Full Text PDFThis study compared the bioavailability of two candidate fixed-dose combinations (FDCs: G003 and G004) of darunavir/cobicistat 800/150 mg with that of darunavir 800 mg and ritonavir 100 mg coadministered as single agents. Short-term safety and tolerability of the FDC formulations were also assessed. This open-label trial included 36 healthy volunteers and assessed steady-state pharmacokinetics of darunavir over 3 randomized, 10-day treatment sequences, under fed conditions.
View Article and Find Full Text PDFObjective: To evaluate serum pharmacokinetics of tapentadol administered to healthy subjects as extended-release (ER) tablets.
Design: Seven single-dose studies (five randomized, crossover, bioequivalence studies; a study in Japanese men; and a randomized, crossover, effects-of-food study) and one repeated-dose study.
Setting: Clinical research settings in the United States and The Netherlands.
Postmortem redistribution of fentanyl in the rabbit was investigated after application of the 50-μg/h Durogesic pain patch. Patches were applied for 48 hours. Two cycles of patch administration were used before characterization of the postmortem redistribution.
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