Clinical pharmacokinetics, pharmacodynamics, safety, and tolerability of JNJ-54175446, a brain permeable P2X7 antagonist, in a randomised single-ascending dose study in healthy participants.

Background: Central nervous system-derived interleukin-1β plays a role in mood disorders. P2X7 receptor activation by adenosine-triphosphate leads to the release of interleukin-1β.

Aims: This first-in-human study evaluated safety, tolerability, pharmacokinetics and pharmacodynamics of a novel central nervous system-penetrant P2X7 receptor antagonist, JNJ-54175446, in healthy participants.

Effect of intranasal esketamine on cognitive functioning in healthy participants: a randomized, double-blind, placebo-controlled study.

Background: The effect of intranasal esketamine on cognitive functioning in healthy participants is assessed in this study.

Methods: Twenty-four participants (19-49 years) were randomized to one of two treatment sequences in which either esketamine 84 mg or placebo was intranasally administered in a double-blind, two-period crossover design. Primary measures included five tests of Cogstate computerized test battery assessed at 1 h predose and 40 min, 2, 4, and 6 h postdose.

Intravenous Esketamine in Adult Treatment-Resistant Depression: A Double-Blind, Double-Randomization, Placebo-Controlled Study.

Background: The purpose of this study was to assess the efficacy and safety and to explore the dose response of esketamine intravenous (IV) infusion in patients with treatment-resistant depression (TRD).

Methods: This multicenter, randomized, placebo-controlled trial was conducted in 30 patients with TRD. Patients were randomly assigned 1:1:1 to receive an IV infusion of .

Comparing proton treatment plans of pediatric brain tumors in two pencil beam scanning nozzles with different spot sizes.

Target coverage and organ-at-risk sparing were compared for 22 pediatric patients with primary brain tumors treated using two distinct nozzles in pencil beam scanning (PBS) proton therapy. Consecutive patients treated at our institution using a PBS-dedicated nozzle (DN) were replanned using a universal nozzle (UN) beam model and the original DN plan objectives. Various cranial sites were treated among the patients to prescription doses ranging from 45 to 54 Gy.

Evaluation of JNJ-26489112 in patients with photosensitive epilepsy: a placebo-controlled, exploratory study.

Purpose: To evaluate the activity of JNJ-26489112 in patients with photosensitive epilepsy and determine the doses that result in reduction or complete suppression of the intermittent photic stimulation (IPS) induced photoparoxysmal-EEG response (PPR).

Methods: In this multicenter, single-blind, within subject, placebo-controlled, sequential dose, exploratory study, 12 adult patients (3 men; 9 women) with idiopathic photosensitive epilepsy, with and without concomitant antiepileptic drug (AED) therapy, underwent standardized IPS under three eye conditions (open, during closure, and closed) for up to 12h after receiving a single oral dose of placebo on day 1, JNJ-26489112 on day 2, and a second dose of placebo on day 3. Based on review of the blinded EEG data, the standardized photosensitive range (SPR) (i.

Modeling the long-term antibody response of a human papillomavirus (HPV) virus-like particle (VLP) type 16 prophylactic vaccine.

The duration over which antibody responses persist following HPV vaccination is unknown. To estimate the longevity of responses induced by HPV-16 vaccination, two models were fitted to serum anti-HPV-16 levels measured during a 48-month study period. The first was a conventional model of antibody decay and the second was a modified model that accounts for long-lived immune memory.

Pharmacokinetics of ertapenem in patients with varying degrees of renal insufficiency and in patients on hemodialysis.

Ertapenem is a parenteral beta-lactam carbapenem antibiotic. This open-label study examined the pharmacokinetics of single 1-g intravenous doses of ertapenem, administered over 30 minutes, in patients with mild, moderate, and advanced renal insufficiency (RI) and in patients with end-stage renal disease (ESRD) requiring hemodialysis. Pharmacokinetics were compared with historical controls pooled across healthy young and elderly subjects.

Disposition of caspofungin: role of distribution in determining pharmacokinetics in plasma.

The disposition of caspofungin, a parenteral antifungal drug, was investigated. Following a single, 1-h, intravenous infusion of 70 mg (200 microCi) of [(3)H]caspofungin to healthy men, plasma, urine, and feces were collected over 27 days in study A (n = 6) and plasma was collected over 26 weeks in study B (n = 7). Supportive data were obtained from a single-dose [(3)H]caspofungin tissue distribution study in rats (n = 3 animals/time point).