Population Pharmacokinetic Modeling of JNJ-53718678, a Novel Fusion Inhibitor for the Treatment of Respiratory Syncytial Virus: Results from a Phase I, Double-Blind, Randomized, Placebo-Controlled First-in-Human Study in Healthy Adult Subjects

Clinical Pharmacokinetics

Volumn 56, Issue 11, 2017, Pages 1331-1342

  Huntjens, Dymphy R H ^a   Ouwerkerk Mahadevan, Sivi ^a   Brochot, Anne ^a   Rusch, Sarah ^a   Stevens, Marita ^a   Verloes, Rene ^a  

^a JANSSEN RESEARCH FOUNDATION   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIVIRUS AGENT; JNJ 53718678; PLACEBO; UNCLASSIFIED DRUG; IMIDAZOLIDINE DERIVATIVE; INDOLE DERIVATIVE; JNJ-53718678;

ADULT; AREA UNDER THE CURVE; ARTICLE; BLOOD SAMPLING; CONTROLLED STUDY; DOUBLE BLIND PROCEDURE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG DISTRIBUTION; DRUG DOSE ESCALATION; DRUG ELIMINATION; DRUG EXCRETION; DRUG HALF LIFE; DRUG URINE LEVEL; FEMALE; HUMAN; HUMAN EXPERIMENT; LIQUID CHROMATOGRAPHY-MASS SPECTROMETRY; MALE; MAXIMUM PLASMA CONCENTRATION; NORMAL HUMAN; PHASE 1 CLINICAL TRIAL; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RESPIRATORY SYNCYTIAL VIRUS INFECTION; TIME TO MAXIMUM PLASMA CONCENTRATION; URINE SAMPLING; ADOLESCENT; BIOLOGICAL MODEL; BLOOD; CLINICAL TRIAL; DOSE RESPONSE; DRUG EFFECT; MIDDLE AGED; PNEUMOVIRUS; URINE; YOUNG ADULT;

ADOLESCENT; ADULT; ANTIVIRAL AGENTS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; FEMALE; HEALTHY VOLUNTEERS; HUMANS; IMIDAZOLIDINES; INDOLES; MALE; MIDDLE AGED; MODELS, BIOLOGICAL; RESPIRATORY SYNCYTIAL VIRUSES; YOUNG ADULT;

EID: 85013831598     PISSN: 03125963     EISSN: 11791926     Source Type: Journal    
DOI: 10.1007/s40262-017-0522-8     Document Type: Article

References (15)

1. Enders G. Chapter 59. Paramyxoviruses. In: Baron S, editor. Medical microbiology. 4th ed. Galveston, Tex: University of Texas Medical Branch at Galveston; 1996.
2. Mazur NI, Martinón-Torres F, Baraldi E, in collaboration with Respiratory Syncytial Virus Network (ReSViNET), et al. Lower respiratory tract infection caused by respiratory syncytial virus: current management and new therapeutics. Lancet. Respir Med. 2015;3:888–900.
3. Nair H, Nokes JD, Gessner BD, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010;375:1545–55.
4. National Center for Immunization and Respiratory Diseases (NCIRD), Division of Viral Diseases. 2014. Available from: http://www.cdc.gov/rsv/about/index.html. Accessed 15 Mar 2016.
5. Paes BA, Mitchell I, Banerji A, et al. A decade of respiratory syncytial virus epidemiology and prophylaxis: translating evidence into everyday clinical practice. Can Respir J. 2011;18:e10–9.
6. Falsey AR, Hennessey PA, Formica MA, et al. Respiratory syncytial virus infection in the elderly and high-risk adults. N Engl J Med. 2005;352:1749–59.
7. Bagga B, Woods CW, Veldman TH, et al. Comparing influenza and RSV viral and disease dynamics in experimentally infected adults predicts clinical effectiveness of RSV antivirals. Antivir Ther. 2013;18:785–91.
8. McLellan JS, Ray WC, Peeples ME. Structure and function of RSV surface glycoproteins. Curr Top Microbiol Immunol. 2013;372:83–104.
9. Roymans D, Rigaux P, Kwanten L, et al. Discovery of JNJ-53718678, a potent inhibitor of RSV. 9th International Respiratory Syncytial Virus Symposium: Cape Town; 9–13 Nov 2014.
10. Ackermann M, Alnajjar S, Larios-Mora A, et al. Therapeutic efficacy of JNJ-53718678, a RSV fusion inhibitor, in neonatal lambs. 10th International Respiratory Syncytial Virus Symposium; Patagonia; 28 Sept–1 Oct 2016.
11. Lindbom L, Pihlgren P, Jonsson EN. PsN-Toolkit: a collection of computer intensive statistical methods for non-linear mixed effect modeling using NONMEM. Comput Methods Programs Biomed. 2005;79(3):241–57.
12. Bergstrand M, Hooker AC, Wallin JE, Karlsson MO. Prediction-corrected visual predictive checks for diagnosing nonlinear mixed-effects models. AAPS J. 2011;13(2):143–51.
13. Björkhem-Bergman L, Bäckström T, Nylén H, et al. Comparison of endogenous 4β-hydroxycholesterol with midazolam as markers for CYP3A4 induction by rifampicin. Drug Metab Dispos. 2013;41(8):1488–93.
14. WHO Toxicity Grading Scale for determining the severity of adverse events. In: ICTDR investigator manual: monitoring and reporting of adverse events. February 2003, p. 45. Available from: http://www.icssc.org/Documents/Resources/ICTDR_AE_Manual_February_6_2003_final.pdf. Accessed 2 Mar 2016.
15. Dressman JB, Berardi RR, Dermentzoglou LC, et al. Upper gastrointestinal (GI) pH in young, healthy men and women. Pharm Res. 1990;7(7):756–61.