Administration of oxathridine, a first-in-class histamine-3 receptor partial agonist in healthy male volunteers: Central nervous system depression and pseudo-hallucinations.

Aims: To characterise the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single ascending doses of oxathridine, a first-in-class histamine-3 receptor partialagonist, in healthy male volunteers.

Methods: A randomised, double-blind, placebo-controlled study including the NeuroCart, consisting of a battery of drug sensitive neurophysiological tests, was performed. Oxathridine was administered orally as an aqueous solution.

Determination of the Optimal Single Dose Treatment for Acoziborole, a Novel Drug for the Treatment of Human African Trypanosomiasis: First-in-Human Study.

Background And Objectives: Acoziborole is a novel boron-containing candidate developed as an oral drug for the treatment of human African trypanosomiasis (HAT). Results from preclinical studies allowed progression to Phase 1 trials. We aimed to determine the best dose regimen for all stages of HAT.

Bioavailability and cardiovascular effects of adrenaline administered by Anapen 500 μg auto-injector in healthy volunteers.

Aims: Anaphylaxis guidelines recommend intramuscular adrenaline, commonly 300 μg administered using an auto-injector device. However, overweight/obese patients may require a higher adrenaline dose for adequate cardiovascular (CV) response. This study evaluated the pharmacokinetics (PK) and pharmacodynamic (PD) CV profiles after a single 500 μg adrenaline injection via Anapen auto-injector in healthy normal weight males and otherwise healthy, overweight or obese females.

Exploring occupancy of the histamine H receptor by pitolisant in humans using PET.

Background And Purpose: BF2.649 (pitolisant, Wakix®) is a novel histamine H receptor inverse agonist/antagonist recently approved for the treatment of narcolepsy disorder. The objective of the study was to investigate in vivo occupancy of H receptors by BF2.

Pharmacokinetics of pitolisant in children and adolescents with narcolepsy.

Objective: To evaluate the pharmacokinetic profile and tolerability of pitolisant, a selective histamine 3 (H)-receptor antagonist/inverse agonist, in children and adolescents with narcolepsy.

Methods: This multicenter, open-label, single-dose study of pitolisant 17.8 mg enrolled patients aged 6 through 17 years with a diagnosis of narcolepsy.

Occupancy of dopamine D and D receptors by a novel D3 partial agonist BP1.4979: a [C]-(+)-PHNO PET study in humans.

There has been considerable interest in the development of dopamine D3 receptor (DRD) partial agonists and antagonists for the treatment of substance use disorders. Pre-clinical evidence overwhelmingly supports the use of these drugs, but translation to humans has remained elusive due to the lack of selective compounds that are suitable for use in humans. Although it has been established for full antagonists, little in vivo occupancy data are available with DRD partial agonists.

Bioavailability and Cardiovascular Effects of Adrenaline Administered by Anapen Autoinjector in Healthy Volunteers.

Background: The administration of adrenaline is a life-saving intervention for anaphylactic reactions. However, it has been questioned whether the needle length of the autoinjectors is sufficient to achieve genuine intramuscular delivery and optimal bioavailability.

Objective: To assess the adequacy of Anapen, which has a relatively short needle length (10.

Can an early phase clinical pharmacology study replace a thorough QT study? Experience with a novel H3-receptor antagonist/inverse agonist.

Objective: The objective of the present study was to compare the effects of pitolisant on QTcF interval in a single ascending dose (SAD) study and a thorough QT (TQT) study.

Methods: The SAD study at three dose levels of pitolisant enrolled 24 males and the TQT study at two dose levels 25 males. Both studies intensively monitored ECGs and pitolisant exposure.

Establishing assay sensitivity in QT studies: experience with the use of moxifloxacin in an early phase clinical pharmacology study and comparison with its effect in a thorough QT study.

Objective: To compare the effect of moxifloxacin as a positive control in a single ascending dose (SAD) study with that in a thorough QT (TQT) study.

Methods: Moxifloxacin was used as a positive control in a SAD study and a TQT study during the evaluation of the QT liability of a new drug. The SAD study had enrolled 24 males and the TQT study 25 males.

Pharmacokinetic drug interactions with vandetanib during coadministration with rifampicin or itraconazole.

Background: Vandetanib, an inhibitor of vascular endothelial growth factor receptor 2 (VEGFR-2), epidermal growth factor receptor (EGFR), and rearranged during transfection (RET), is a developmental oncology drug, that is in part metabolized by cytochrome P450 (CYP) 3A4. Clinical studies were performed to assess the potential for 3A4 inhibitors and inducers to affect exposure to vandetanib.

Objective: The aim of this study was to investigate the effects of a potent CYP3A4 inducer, rifampicin (Study A), and a potent CYP3A4 inhibitor, itraconazole (Study B), on the pharmacokinetics of a single 300 mg dose of vandetanib in healthy subjects.

Single-dose clinical pharmacokinetic studies of gefitinib.

Background: The objective of the five clinical studies presented in this article was to investigate the single-dose pharmacokinetics of gefitinib (IRESSA, ZD1839), an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, in healthy volunteers and patients with advanced cancer.

Methods: Studies 1 and 3-5 recruited healthy male volunteers aged 18-65 years; study 2 recruited male or female patients aged>or=18 years with any solid malignant tumour expressing EGFR and refractory to standard therapy. Gefitinib administration was as follows: study 1 (bioavailability in healthy volunteers; n=12)--intravenous infusion of 50 or 100 mg followed by a single oral dose of 250 mg; study 2 (bioavailability in cancer patients; n=19)--intravenous infusion of 50 mg followed by a single oral dose of 250 mg; study 3 (intrasubject variability; n=24)--two single oral doses of 250 mg; study 4 (dose-proportionality; n=15)--three single oral doses of 50-500 mg; study 5 (effect of food; n=26)--two single doses of 250 mg under either fed or fasted conditions.

Absence of interaction of fondaparinux sodium with aspirin and piroxicam in healthy male volunteers.

Objective: Patients undergoing major orthopaedic surgery who are being treated with fondaparinux sodium for prevention of venous thromboembolism may be receiving treatment for coronary artery disease or chronic inflammatory disease of the joints or arthritis. Two separate studies assessed any possible interaction between fondaparinux sodium at steady state and aspirin (acetylsalicylic acid) or piroxicam in healthy volunteers.

Design: In the first study a single dose of aspirin 975mg was assessed initially, followed by single doses of aspirin or placebo on the fourth day of an 8-day regimen of subcutaneous fondaparinux sodium (10mg once daily).