Losmapimod concentration-QT relationship in healthy volunteers: Meta-analysis of data from six clinical trials

European Journal of Clinical Pharmacology

Volumn 69, Issue 6, 2013, Pages 1261-1267

  Yang, Shuying ^a   Beerahee, Misba ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

Concentration QT relationship; Losmapimod; Meta analysis; Population pharmacokinetic pharmacodynamic model; QT

Indexed keywords

LOSMAPIMOD; PLACEBO; ROSUVASTATIN;

ADULT; AGED; ARTICLE; COHORT ANALYSIS; CONTROLLED STUDY; COVARIANCE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG ELIMINATION; DRUG METABOLISM; DRUG POTENTIATION; ELECTROCARDIOGRAPHY; FEMALE; HEART RATE; HUMAN; HUMAN EXPERIMENT; MALE; META ANALYSIS; NORMAL HUMAN; PHASE 1 CLINICAL TRIAL; POPULATION MODEL; PRIORITY JOURNAL; QT INTERVAL; QT PROLONGATION; REPEATED DRUG DOSE; SEX DIFFERENCE; SINGLE DRUG DOSE; VOLUNTEER;

ADOLESCENT; ADULT; AGED; CLINICAL TRIALS AS TOPIC; CYCLOPROPANES; DOSE-RESPONSE RELATIONSHIP, DRUG; ELECTROCARDIOGRAPHY; FEMALE; HEART RATE; HUMANS; LONG QT SYNDROME; MALE; MIDDLE AGED; MODELS, BIOLOGICAL; PROTEIN KINASE INHIBITORS; PYRIDINES; RISK ASSESSMENT; RISK FACTORS; YOUNG ADULT;

EID: 84878014048     PISSN: 00316970     EISSN: 14321041     Source Type: Journal    
DOI: 10.1007/s00228-012-1469-1     Document Type: Article

References (17)

1. US Food and Drug Administration (2005) International Conference on Harmonisation. Guidance on E14 clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs; availability. Notice. Fed Regist 70:61134-61135
2. Chapel S, Hutmacher MM, Bockbrader H, de Greef R, Lalonde RL (2011) Comparison of QTc data analysis methods recommended by the ICH E14 guidance and exposure-response analysis: case study of a thorough QT study of asenapine. Clin Pharmacol Ther 89:75-80
3. Darpo B (2010) The thorough QT/QTc study 4 years after the implementation of the ICH E14 guidance. Br J Pharmacol 159:49-57
4. Piotrovsky V (2005) Pharmacokinetic-pharmacodynamic modeling in the data analysis and interpretation of drug-induced QT/QTc prolongation. AAPS J 7(3):E609-E624
5. Hutmacher MM, Chapel S, Agin MA, Fleishaker JC, Lalonde RL (2008) Performance characteristics for some typical QT study designs under the ICH E-14 guidance. J Clin Pharmacol 48:215-224
6. Salvi V, Karnad DR, Panicker GK, Kothari S (2010) Update on the evaluation of a new drug for effects on cardiac repolarization in humans: issues in early drug development. Br J Pharmacol 159(1):34-48
7. Chain ASY, Krudys KM, Danhof M, Pasqua OD (2011) Assessing the probability of drug-induced QTc-interval prolongation during clinical drug development. Clin Pharmacol Ther 90:867-875
8. Russell T, Riley SP, Cook JA, Lalonde RL (2008) A perspective on the use of concentration-QT modeling in drug development. J Clin Pharmacol 48:9-12
9. Garnett CE, Beasley N, Bhattaram A, et al. (2008) Concentration-QT relationships play a key role in the evaluation of proarrhythmic risk during regulatory review. J Clin Pharmacol 48:13-18
10. Rohatagi S, Carrothers T, Juwabara-Wagg J, Khariton T (2009) Is a thorough QTc study necessary? The role of modeling and simulation in evaluating the QTc prolongation potential of drugs. J Clin Pharmacol 49(11):1284-1296
11. GlaxoSmithKline (2010) ClinicalTrials.gov Identifier NCT01218126. Randomised, double-blind, placebo-controlled, parallel-group, multi-centre, dose ranging study to evaluate the efficacy and safety of losmapimod tablets administered twice daily compared with placebo for 24 weeks in adult subjects with chronic obstructive pulmonary disease (COPD). GlaxoSmithKline, London
12. Lomas DA, Lipson DA, Miller BE, Willits L, Keene O, Barnacle H, Barnes NC, Tal-Singer R (2012) An oral inhibitor of p38 MAP kinase reduces plasma fibrinogen in patients with chronic obstructive pulmonary disease. J Clin Pharmacol 52(3):416-424
13. ClinicalTrials.gov Identifier: NCT01541852 (2012) Losmapimod in Chronic Obstructive Pulmonary Disease Patients Stratified by Fibrinogen. (EVOLUTION). http://clinicaltrial.gov/ct2/show/NCT01541852?term=losmapimod&rank=3
14. GlaxoSmithKline (2008) ClinicalTrials.gov Identifier NCT00633022. A study to evaluate the effects of 3 months dosing with GW856553, as assessed FDG-PET/CT imaging. GlaxoSmithKline, London
15. Beal S, Sheiner LB, Boeckmann A (eds) (2006) NONMEM user's guides. (1989-2006). Icon Development Solutions, Ellicott City
16. Murray A, McLaughlin NB, Campbell RWF (1997) Measuring QT dispersion: man versus machine. Heart 77:539-542
17. Fosser C, Duczynski G, Agin M, Wicker P, Darpo B (2009) Comparison of manual and automated measurements of the QT interval in healthy volunteers: an analysis of five thorough QT studies. Clin Pharmacol Ther 86:503-506