British journal of clinical pharmacology
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Br J Clin Pharmacol · Sep 2019
Randomized Controlled Trial Multicenter StudyEffects of CYP3A inhibitors on the pharmacokinetics of quizartinib, a potent and selective FLT3 inhibitor, and its active metabolite.
Quizartinib is an oral, highly potent and selective next-generation FMS-like tyrosine kinase 3 (FLT3) inhibitor under investigation in patients with FLT3-internal tandem duplication-mutated acute myeloid leukaemia. This drug-drug interaction study assessed the pharmacokinetics (PK) of quizartinib when coadministered with strong or moderate cytochrome P450 3A (CYP3A) inhibitors. ⋯ These results suggest reducing the dose of quizartinib when coadministered with a strong CYP3A inhibitor, but not with a moderate or weak CYP3A inhibitor. This dose reduction was implemented in phase 3 evaluation of quizartinib.
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Br J Clin Pharmacol · Jul 2019
Randomized Controlled TrialA randomized double-blind, placebo-controlled clinical phase IIa trial on safety, immunomodulatory effects and pharmacokinetics of EA-230 during experimental human endotoxaemia.
EA-230 is a human chorionic gonadotropin hormone-derived linear tetrapeptide, developed for the treatment of systemic inflammation-related disorders. EA-230 has shown promising immunomodulatory and tissue-protective effects in animals and an excellent safety profile in human phase I studies that we performed. The present phase IIa study follows-up on these results by investigating the safety, efficacy and pharmacokinetics of EA-230 under systemic inflammatory conditions induced by experimental human endotoxaemia. ⋯ Administration of EA-230 is safe and results in attenuation of the systemic inflammatory response in humans.
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Br J Clin Pharmacol · Mar 2019
Randomized Controlled Trial Multicenter StudyEffect of inotuzumab ozogamicin on the QT interval in patients with haematologic malignancies using QTc-concentration modelling.
The aim of this study was to characterize the effect of inotuzumab ozogamicin on QT interval in patients with B-cell malignancies. ⋯ Inotuzumab ozogamicin (1.8 mg m-2 per cycle) is not predicted to pose a clinically significant safety risk for QT prolongation in patients with acute lymphoblastic leukaemia or non-Hodgkin lymphoma.
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Br J Clin Pharmacol · Oct 2018
Randomized Controlled TrialMEDI0382, a GLP-1/glucagon receptor dual agonist, meets safety and tolerability endpoints in a single-dose, healthy-subject, randomized, Phase 1 study.
MEDI0382 is a balanced glucagon-like peptide-1/glucagon receptor dual agonist under development for the treatment of type 2 diabetes mellitus and non-alcoholic steatohepatitis. The primary objective was to assess the safety of MEDI0382 in healthy subjects. ⋯ In this single-dose, Phase 1 study in healthy subjects, the safety and pharmacokinetic profiles of MEDI0382 support once-daily dosing and further clinical development of MEDI0382.
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Br J Clin Pharmacol · Sep 2018
Randomized Controlled TrialSafety, tolerability and pharmacokinetics/pharmacodynamics of the adrenomedullin antibody adrecizumab in a first-in-human study and during experimental human endotoxaemia in healthy subjects.
Adrenomedullin (ADM) is an important regulator of endothelial barrier function and vascular tone, and may represent a novel treatment target in sepsis. The non-neutralizing ADM antibody adrecizumab has shown promising results in preclinical sepsis models. In the present study, we investigated the safety, tolerability and pharmacokinetics (PK)/pharmacodynamics of adrecizumab in a first-in-man study and in a second study during experimental human endotoxaemia. ⋯ Administration of adrecizumab is safe and well tolerated in humans, both in the absence and presence of systemic inflammation. These findings pave the way for further investigation of adrecizumab in sepsis patients.