Estimation of the Power of the Food Effect on QTc to Show Assay Sensitivity.

Abstract:

:The most recent International Conference on Harmonisation E14 Q&A document states that a separate positive control would not be necessary provided sufficiently high exposures are achieved in the early-phase studies. Realistically, a phase 1 study is unlikely to include a pharmacological positive control, and in cases in which plasma levels of the drug exceeding therapeutic levels are not achieved, the lack of a positive control can constitute a limitation when excluding an effect of regulatory concern. It has been proposed to use the effect of a standardized meal on the estimate of the diurnal time course of QTc to show assay sensitivity. We conducted simulations by subsampling subjects from a 3 different studies and could show that the effect on food on QTc can be reliably prove assay sensitivity for sample sizes as low as 3 × 6 subjects with a power greater than 80%.

journal_name

J Clin Pharmacol

authors

Ferber G,Fernandes S,Täubel J

doi

10.1002/jcph.975

subject

Has Abstract

pub_date

2018-01-01 00:00:00

pages

81-88

issue

1

eissn

0091-2700

issn

1552-4604

journal_volume

58

pub_type

杂志文章,随机对照试验
  • A computer-based, problem-solving system of instruction in clinical pharmacology.

    abstract::Advances in microcomputer technology provide new ways of incorporating PBL procedures in clinical pharmacology courses. Developments in graphics-user interfaces and analog/digital systems that display physiologic information directly on the monitor enable the computer to serve as a learning resource as laboratory clas...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1991.tb04962.x

    authors: Hutcheon DE,el-Gawly HW

    更新日期:1991-03-01 00:00:00

  • Population pharmacokinetics of ceftaroline in patients with acute bacterial skin and skin structure infections or community-acquired bacterial pneumonia.

    abstract::Ceftaroline, the active form of ceftaroline fosamil, is a broad-spectrum cephalosporin antibiotic. A population pharmacokinetic (PPK) model for ceftaroline was developed in NONMEM® using data from 185 healthy subjects and 92 patients with acute bacterial skin and skin structure infection (ABSSSI). Data from 128 patien...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,多中心研究,随机对照试验

    doi:10.1002/jcph.153

    authors: Van Wart SA,Forrest A,Khariton T,Rubino CM,Bhavnani SM,Reynolds DK,Riccobene T,Ambrose PG

    更新日期:2013-11-01 00:00:00

  • A Population Pharmacokinetic Model of Oral Docetaxel Coadministered With Ritonavir to Support Early Clinical Development.

    abstract::Oral administration of docetaxel is an attractive alternative for conventional intravenous (IV) administration. The low bioavailability of docetaxel, however, hinders the application of oral docetaxel in the clinic. The aim of the current study was to develop a population pharmacokinetic (PK) model for docetaxel and r...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1532

    authors: Yu H,Janssen JM,Sawicki E,van Hasselt JGC,de Weger VA,Nuijen B,Schellens JHM,Beijnen JH,Huitema ADR

    更新日期:2020-03-01 00:00:00

  • Tafenoquine at therapeutic concentrations does not prolong Fridericia-corrected QT interval in healthy subjects.

    abstract::Tafenoquine is being developed for relapse prevention in Plasmodium vivax malaria. This Phase I, single-blind, randomized, placebo- and active-controlled parallel group study investigated whether tafenoquine at supratherapeutic and therapeutic concentrations prolonged cardiac repolarization in healthy volunteers. Subj...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/jcph.302

    authors: Green JA,Patel AK,Patel BR,Hussaini A,Harrell EJ,McDonald MJ,Carter N,Mohamed K,Duparc S,Miller AK

    更新日期:2014-09-01 00:00:00

  • Clinical Pharmacokinetic and Pharmacodynamic Overview of Nilotinib, a Selective Tyrosine Kinase Inhibitor.

    abstract::Nilotinib, an oral inhibitor of the tyrosine kinase activity of Abelson protein, is approved for the treatment of patients with newly diagnosed chronic myeloid leukemia (CML) in chronic phase and patients with CML in chronic phase or accelerated phase resistant or intolerant to prior therapies. This review describes t...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/jcph.1312

    authors: Tian X,Zhang H,Heimbach T,He H,Buchbinder A,Aghoghovbia M,Hourcade-Potelleret F

    更新日期:2018-12-01 00:00:00

  • Local Investigators Significantly Overestimate Overall Response Rates Compared to Blinded Independent Central Reviews in Phase 2 Oncology Trials.

    abstract::The overall response rate (ORR) is a largely adopted outcome measure in early-phase oncology trials. ORR is highly relevant in cancer drug development at the time of deciding whether to move to confirmatory phase 3 trials; moreover, ORR is gaining increasing relevance in fast-track registration procedures. No systemat...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1790

    authors: Dello Russo C,Cappoli N,Pilunni D,Navarra P

    更新日期:2020-11-26 00:00:00

  • An evaluation of the dose-dependent inhibition of CYP1A2 by rofecoxib using theophylline as a CYP1A2 probe.

    abstract::This study was undertaken to determine whether rofecoxib can interfere with CYP1A2 activity in humans using theophylline as a probe substrate. Single oral doses of theophylline were administered to each of three panels of 12 healthy subjects receiving daily doses of rofecoxib for 7 days to examine the effect of rofeco...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1177/0091270003257454

    authors: Bachmann K,White D,Jauregui L,Schwartz JI,Agrawal NG,Mazenko R,Larson PJ,Porras AG

    更新日期:2003-10-01 00:00:00

  • Pregnancy-induced changes in the long-term pharmacokinetics of 1.1 mg vs. 5 mg folic acid: a randomized clinical trial.

    abstract::The objective of this randomized clinical trial was to compare steady-state gestational RBC and plasma folate concentrations in pregnant women supplementing daily with 1.1 mg (regular dose) vs. 5 mg (high dose) folic acid. Thirty-seven pregnant women, who were not previously taking folic acid, were enrolled in this op...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1002/jcph.387

    authors: Shere M,Nguyen P,Tam C,Stern S,Kapur B,O'Connor DL,Koren G

    更新日期:2015-02-01 00:00:00

  • Labetalol in the treatment of essential hypertension: a single-blind dose ranging study.

    abstract::The hypotensive efficacy of labetalol was evaluated in 29 patients with essential hypertension in a single-blind dose ranging study. After a two-week period of placebo treatment, labetalol was given in oral doses of 0.6 g/d, 0.8 g/d, and 0.8 g/d combined with 25-50 mg/d of hydrochlorothiazide. Each regimen lasted four...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1986.tb03536.x

    authors: Dux S,Grosskopf I,Boner G,Rosenfeld JB

    更新日期:1986-05-01 00:00:00

  • Pharmacokinetic interactions of concomitant administration of febuxostat and NSAIDs.

    abstract::To evaluate the effect of febuxostat on the pharmacokinetics of indomethacin and naproxen and vice versa, 2 multiple-dose, 3-period crossover studies were performed in healthy subjects. In study 1, subjects received febuxostat 80 mg once daily, indomethacin 50 mg twice daily, or both. In study 2, subjects received feb...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1177/0091270006289848

    authors: Khosravan R,Wu JT,Joseph-Ridge N,Vernillet L

    更新日期:2006-08-01 00:00:00

  • Population pharmacokinetic analysis and simulation of the time-concentration profile of etanercept in pediatric patients with juvenile rheumatoid arthritis.

    abstract::This study was performed to estimate the population pharmacokinetic (PK) parameters of etanercept in pediatric juvenile rheumatoid arthritis (JRA) patients and to compare the steady-state time-concentration profiles between etanercept 0.8-mg/kg once-weekly and 0.4-mg/kg twice-weekly subcutaneous (SC) regimens by clini...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/0091270004271945

    authors: Yim DS,Zhou H,Buckwalter M,Nestorov I,Peck CC,Lee H

    更新日期:2005-03-01 00:00:00

  • Which studies of therapy merit credence? Vitamin E and estrogen therapy as cautionary examples.

    abstract::A vast and continuously growing amount of material on drugs exists in the literature to read and evaluate. Frequently, the papers and their recommendations are conflicting and contradictory. Readers are faced with the dilemma of deciding what to believe. The need for evidence-based medicine as a foundation for optimal...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:

    authors: Spector R,Vesell ES

    更新日期:2002-09-01 00:00:00

  • Single- and multiple-dose administration of caspofungin in patients with hepatic insufficiency: implications for safety and dosing recommendations.

    abstract::This report investigated safety and dosing recommendations of intravenous caspofungin in hepatic insufficiency. In the single-dose study, 8 patients each with mild and moderate hepatic insufficiency received 70 mg of caspofungin. In the multiple-dose study, 8 patients with mild hepatic insufficiency and 13 healthy mat...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/0091270007303764

    authors: Mistry GC,Migoya E,Deutsch PJ,Winchell G,Hesney M,Li S,Bi S,Dilzer S,Lasseter KC,Stone JA

    更新日期:2007-08-01 00:00:00

  • Comparative inhibitory activity of rofecoxib, meloxicam, diclofenac, ibuprofen, and naproxen on COX-2 versus COX-1 in healthy volunteers.

    abstract::Steady-state inhibitory activity of rofecoxib (Vioxx) on COX-2 versus COX-1 was compared with that of commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) in 76 healthy volunteers randomized to placebo, rofecoxib 12.5 mg qd, rofecoxib 25 mg qd, diclofenac 50 mg tid, ibuprofen 800 mg tid, sodium naproxen 550 mg ...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:

    authors: Van Hecken A,Schwartz JI,Depré M,De Lepeleire I,Dallob A,Tanaka W,Wynants K,Buntinx A,Arnout J,Wong PH,Ebel DL,Gertz BJ,De Schepper PJ

    更新日期:2000-10-01 00:00:00

  • Magnitude and nature of noncompliance with treatment using isosorbide dinitrate in patients with ischemic heart disease.

    abstract::Isosorbide dinitrate is one of the most commonly prescribed medications for the treatment of ischemic heart disease. It has been demonstrated to be ineffective relative to placebo when taken inappropriately. This study objectively documents the magnitude and nature of compliance in 68 ambulatory patients who were pres...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1996.tb04222.x

    authors: Straka RJ,Fish JT,Benson SR,Suh JT

    更新日期:1996-07-01 00:00:00

  • Management of hypertensive urgencies and emergencies.

    abstract::Hypertensive emergency is a condition in which there is elevation of both systolic and diastolic blood pressure with the presence of acute target organ disease. Hypertensive urgency is a condition where the blood pressure is elevated (diastolic > 120 mmHg) with the absence of acute target organ disease. Hypertensive e...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/j.1552-4604.1995.tb04116.x

    authors: Abdelwahab W,Frishman W,Landau A

    更新日期:1995-08-01 00:00:00

  • Probiotics in Disease Prevention and Treatment.

    abstract::Few treatments for human diseases have received as much investigation in the past 20 years as probiotics. In 2017, English-language meta-analyses totaling 52 studies determined the effect of probiotics on conditions ranging from necrotizing enterocolitis and colic in infants to constipation, irritable bowel syndrome, ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1121

    authors: Liu Y,Tran DQ,Rhoads JM

    更新日期:2018-10-01 00:00:00

  • Relationships of Changes in Pharmacokinetic Parameters of Substrate Drugs in Drug-Drug Interactions on Metabolizing Enzymes and Transporters.

    abstract::A general objective of drug-drug interaction (DDI) studies is to determine whether potential interactions of new molecular entities with concomitantly administered other drugs exist and, if DDIs occur, whether dosage adjustments are required. A typical end point for DDI evaluations is the ratio of area under the plasm...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1104

    authors: Yamazaki S

    更新日期:2018-08-01 00:00:00

  • Biological activity of cannabichromene, its homologs and isomers.

    abstract::Cannabichromene (CBC) is one of four major cannabinoids in Cannabis sativa L. and is the second most abundant cannabinoid in drug-type cannabis. Cannabichromene and some of its homologs, analogs, and isomers were evaluated for antiinflammatory, antibacterial, and antifungal activity. Antiinflammatory activity was eval...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1981.tb02606.x

    authors: Turner CE,Elsohly MA

    更新日期:1981-08-01 00:00:00

  • Cardiovascular responses to standing: effect of hydration.

    abstract::Many astronauts experience intolerance to orthostatic stress after space flight, despite the ingestion of salt tablets and water equivalent to 0.9% saline just before their return to Earth. Previous research indicates that the ingestion of 1.07% saline solution increased plasma volume more than did 0.9% saline. Theref...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1994.tb04978.x

    authors: Frey MA,Lathers C,Davis J,Fortney S,Charles JB

    更新日期:1994-05-01 00:00:00

  • Clinical pharmacokinetics of the CD19 receptor-directed tyrosine kinase inhibitor B43-Genistein in patients with B-lineage lymphoid malignancies.

    abstract::The authors examined the pharmacokinetics of the CD19 receptor-directed tyrosine kinase inhibitor B43-Genistein in 17 patients (4 children, 13 adults) with B-lineage lymphoid malignancies, including 12 patients with acute lymphoblastic leukemia (ALL) and 5 patients with non-Hodgkin's lymphoma (NHL). The immunoconjugat...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1177/00912709922012051

    authors: Chen CL,Levine A,Rao A,O'Neill K,Messinger Y,Myers DE,Goldman F,Hurvitz C,Casper JT,Uckun FM

    更新日期:1999-12-01 00:00:00

  • Randomized Population Pharmacokinetic Analysis and Safety of Intravenous Acetaminophen for Acute Postoperative Pain in Neonates and Infants.

    abstract::Intravenous administration of acetaminophen is an alternative to the oral and rectal routes, which may be contraindicated in particular clinical settings. This randomized, placebo-controlled study of intravenous acetaminophen (Ofirmev, Mallinckrodt Pharmaceuticals, Bedminster, New Jersey) in neonate and infant patient...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/jcph.1508

    authors: Hammer GB,Maxwell LG,Taicher BM,Visoiu M,Cooper DS,Szmuk P,Pheng LH,Gosselin NH,Lu J,Devarakonda K

    更新日期:2020-01-01 00:00:00

  • Clinical and bacteriological evaluation of amikacin in severe gram-negative infections.

    abstract::Amikacin was administered to 51 patients with serious Gram-negative infections. A favorable clinical outcome was observed in 32 patients (62 per cent). No major untoward effects were noted. The severity of the underlying disease and the site of the infection were important for the outcome. Urinary tract infections res...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1002/j.1552-4604.1976.tb01520.x

    authors: Klastersky J,Van Beerse D,Schoutens E,De Temmerman P,Yourassowsky E

    更新日期:1976-04-01 00:00:00

  • The pharmacokinetics of sodium oxybate oral solution following acute and chronic administration to narcoleptic patients.

    abstract::This trial was conducted to evaluate the pharmacokinetics and safety of a sodium oxybate (gamma-hydroxybutyrate [GHB]) oral solution in narcoleptic patients after acute and chronic treatment. An open-label, two-period, two-treatment study design was used. Trial subjects included 13 patients with polysomnographically c...

    journal_title:Journal of clinical pharmacology

    pub_type: 临床试验,杂志文章

    doi:10.1177/0091270003262795

    authors: Borgen LA,Okerholm RA,Lai A,Scharf MB

    更新日期:2004-03-01 00:00:00

  • Pharmacokinetics of capacity-limited systems.

    abstract::Nonlinearities are commonplace in pharmacokinetics and most frequently occur because of a limited concentration of biological material available for interaction with relatively high concentrations of drugs. The Michaelis-Menten-type function can be applied to metabolism, transport, and binding phenomena that display c...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1002/j.1552-4604.1989.tb03369.x

    authors: Jusko WJ

    更新日期:1989-06-01 00:00:00

  • Pharmacodynamics of procainamide in patients with ventricular tachyarrhythmias.

    abstract::The onset and offset of the electropharmacologic effect of procainamide was studied in nine patients with ventricular arrhythmias. Procainamide was given at a constant infusion rate of 0.27 +/- 0.05 mg/kg/min for 50 to 60 minutes to an average total dose of 15.5 +/- 4.4 mg/kg. The QRS interval (used as an index of ele...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1988.tb03118.x

    authors: Liem LB,Yee YG,Swerdlow CD,Kates RE

    更新日期:1988-11-01 00:00:00

  • Human drug metabolism and the cytochromes P450: application and relevance of in vitro models.

    abstract::The cytochromes P450 (CYPs) constitute a superfamily of hemoprotein enzymes that are responsible for the biotransformation of numerous xenobiotics, including therapeutic agents. Studies of the biochemical and enzymatic properties of these enzymes and their molecular genetics and regulation of gene expression and activ...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,评审

    doi:10.1177/00912700122012724

    authors: Venkatakrishnan K,Von Moltke LL,Greenblatt DJ

    更新日期:2001-11-01 00:00:00

  • The application of stable isotopes to studies of drug bioavailability and bioequivalence.

    abstract::The increased availability of chemical intermediates and automated instrumentation has resulted in expanded use of stable isotopes for bioavailability and bioequivalence studies in recent years. Initially, stable isotopes were confined to the labeling of mass internal standard compounds for gas chromatography/mass spe...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1002/j.1552-4604.1986.tb03551.x

    authors: Wolen RL

    更新日期:1986-07-01 00:00:00

  • Population pharmacokinetic model for a novel oral hypoglycemic formed in vivo: comparing the use of active metabolite data alone versus using data of upstream and downstream metabolites.

    abstract::The purpose of this analysis was to develop a population pharmacokinetic model for CS-917, an oral hypoglycemic prodrug, and its 3 metabolites. The population pharmacokinetic model was used to predict exposure of the active moiety R-125338 and thus to identify potential CS-917 dosage reduction criteria. The dataset in...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章

    doi:10.1177/0091270010396373

    authors: Kastrissios H,Walker JR,Carrothers TJ,Kshirsagar S,Khariton T,Habtemariam B,Mager DE,Rohatagi S

    更新日期:2012-03-01 00:00:00

  • Pleiotropic effects of atorvastatin on monocytes in atherosclerotic patients.

    abstract::The objective of this study was to investigate the gene expression signature of monocyte/macrophages and the pleiotropic effects of atorvastatin on monocytes in atherosclerotic patients. Forty patients with coronary heart diseases were randomly assigned to double-blind therapy with either 20 or 80 mg per day of atorva...

    journal_title:Journal of clinical pharmacology

    pub_type: 杂志文章,随机对照试验

    doi:10.1177/0091270009340889

    authors: Wang ZH,Liu XL,Zhong M,Zhang LP,Shang YY,Hu XY,Li L,Zhang Y,Deng JT,Zhang W

    更新日期:2010-03-01 00:00:00