{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T22:22:27Z","timestamp":1793226147400,"version":"4.5.0"},"reference-count":15,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008897","name":"Janssen Pharmaceutica NV","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100008897","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Dengue is a growing global health threat with no specific antiviral drugs available for treatment or prophylaxis. This first-in-human, double-blind, randomized, placebo-controlled study aimed to examine the safety, tolerability, and pharmacokinetics of increasing single and multiple oral doses of JNJ-1802, a pan-serotype dengue antiviral small molecule.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Eligible healthy participants (18\u201355 years of age) were randomized to receive oral JNJ-1802 in fasted conditions as (1) single doses (50\u20131200 mg; n = 29) or placebo (n = 10); or (2) once-daily doses (50\u2013560 mg for 10 consecutive days or 400 mg for 31 days; n = 38) or placebo (n = 9). Safety and tolerability were evaluated throughout the study. Plasma and urine samples were collected at predetermined time points to characterize pharmacokinetics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>JNJ-1802 was generally safe and well-tolerated. One grade 3 adverse event (depression) was reported but not considered drug-related by the investigator. Two grade 2 events of rash occurred (multiple-dose part) that were considered very likely related to JNJ-1802 by the investigator and resolved. No clinically relevant changes were observed in laboratory tests, electrocardiograms, or vital signs.<\/jats:p>\n                    <jats:p>JNJ-1802 exposure after single or multiple doses increased dose-proportionally from 50 to 150 mg and less than dose-proportionally for higher doses. The terminal elimination half-life was 6.3\u20139.2 days and the accumulation factor was 4.3\u20137.3 after 10 days and 14.6 after 31 days with low amounts of unchanged drug in urine (&amp;lt;0.001% of the 400 mg dose).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Pharmacokinetics and safety results of JNJ-1802 support further clinical development for the treatment and prevention of dengue infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cid\/ciad284","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T00:02:11Z","timestamp":1683763331000},"page":"857-865","source":"Crossref","is-referenced-by-count":48,"title":["Safety, Tolerability, and Pharmacokinetics of JNJ-1802, a Pan-serotype Dengue Direct Antiviral Small Molecule, in a Phase 1, Double-Blind, Randomized, Dose-Escalation Study in Healthy Volunteers"],"prefix":"10.1093","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5908-5200","authenticated-orcid":false,"given":"Oliver","family":"Ackaert","sequence":"first","affiliation":[{"name":"Janssen Clinical Pharmacology and Pharmacometrics, Janssen Pharmaceutica NV , Beerse , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Vanhoutte","sequence":"additional","affiliation":[{"name":"SGS Clinical Pharmacology Unit , Antwerp , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Verpoorten","sequence":"additional","affiliation":[{"name":"Global Public Health R&D , Janssen Pharmaceutica NV, Beerse , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annemie","family":"Buelens","sequence":"additional","affiliation":[{"name":"Statistics & Decisions Sciences, Janssen Pharmaceutica NV , Beerse , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Lachau-Durand","sequence":"additional","affiliation":[{"name":"Preclinical Sciences and Translational Safety, Janssen Pharmaceutica NV , Beerse , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lieve","family":"Lammens","sequence":"additional","affiliation":[{"name":"Preclinical Sciences and Translational Safety, Janssen Pharmaceutica NV , Beerse , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Hoetelmans","sequence":"additional","affiliation":[{"name":"Janssen Clinical Pharmacology and Pharmacometrics, Janssen Pharmaceutica NV , Beerse , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4151-4588","authenticated-orcid":false,"given":"Marnix","family":"Van Loock","sequence":"additional","affiliation":[{"name":"Global Public Health R&D , Janssen Pharmaceutica NV, Beerse , Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillermo","family":"Herrera-Taracena","sequence":"additional","affiliation":[{"name":"Global Public Health, Janssen Research and Development , Horsham, PA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,5,10]]},"reference":[{"key":"2024043015494355700_ciad284-B1","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1038\/s41564-019-0476-8","article-title":"The current and future global distribution and population at risk of dengue","volume":"4","author":"Messina","year":"2019","journal-title":"Nat Microbiol"},{"key":"2024043015494355700_ciad284-B2","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/nature12060","article-title":"The global distribution and burden of dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"2024043015494355700_ciad284-B3","author":"World Health Organization","year":"2012"},{"key":"2024043015494355700_ciad284-B4","author":"World mosquito program","year":"2020"},{"key":"2024043015494355700_ciad284-B5","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1056\/NEJMra1110265","article-title":"Dengue","volume":"366","author":"Simmons","year":"2012","journal-title":"N Engl J Med"},{"key":"2024043015494355700_ciad284-B6","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/S1473-3099(14)70730-3","article-title":"Efficacy and safety of celgosivir in patients with dengue fever (CELADEN): a phase 1b, randomised, double-blind, placebo-controlled, proof-of-concept trial","volume":"14","author":"Low","year":"2014","journal-title":"Lancet Infect Dis"},{"key":"2024043015494355700_ciad284-B7","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1007\/978-981-10-8727-1_22","article-title":"Dengue antiviral development: a continuing journey","volume":"1062","author":"Low","year":"2018","journal-title":"Adv Exp Med Biol"},{"key":"2024043015494355700_ciad284-B8","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0003025","article-title":"Dengue therapeutics, chemoprophylaxis, and allied tools: state of the art and future directions","volume":"8","author":"Whitehorn","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"2024043015494355700_ciad284-B9","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/s41586-023-05790-6","article-title":"Blocking NS3\u2013NS4B interaction inhibits dengue virus in non-human primates","volume":"615","author":"Goethals","year":"2023","journal-title":"Nature"},{"key":"2024043015494355700_ciad284-B10","doi-asserted-by":"crossref","first-page":"S96","DOI":"10.1093\/infdis\/jiw423","article-title":"Current status of dengue therapeutics research and development","volume":"215","author":"Low","year":"2017","journal-title":"J Infect Dis"},{"key":"2024043015494355700_ciad284-B11","author":"World Health Organization","year":"2009"},{"key":"2024043015494355700_ciad284-B12","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1093\/jac\/dkm337","article-title":"A systematic review and meta-analysis of the effectiveness and safety of atovaquone proguanil (Malarone) for chemoprophylaxis against malaria","volume":"60","author":"Nakato","year":"2007","journal-title":"J Antimicrob Chemother"},{"key":"2024043015494355700_ciad284-B13","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1007\/978-981-10-8727-1_23","article-title":"An industry perspective on dengue drug discovery and development","volume":"1062","author":"Hernandez-Morales","year":"2018","journal-title":"Adv Exp Med Biol"},{"key":"2024043015494355700_ciad284-B14","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1038\/nrd.2017.33","article-title":"Broad-spectrum agents for flaviviral infections: dengue, Zika and beyond","volume":"16","author":"Boldescu","year":"2017","journal-title":"Nat Rev Drug Discov"},{"key":"2024043015494355700_ciad284-B15","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.coviro.2020.07.009","article-title":"Recent advances in antiviral drug development towards dengue virus","volume":"43","author":"Troost","year":"2020","journal-title":"Curr Opin Virol"}],"container-title":["Clinical Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/cid\/advance-article-pdf\/doi\/10.1093\/cid\/ciad284\/50500331\/ciad284.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/77\/6\/857\/57361762\/ciad284.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/cid\/article-pdf\/77\/6\/857\/57361762\/ciad284.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T11:50:48Z","timestamp":1714477848000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/cid\/article\/77\/6\/857\/7158803"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,10]]},"references-count":15,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,5,10]]},"published-print":{"date-parts":[[2023,9,18]]}},"URL":"https:\/\/doi.org\/10.1093\/cid\/ciad284","relation":{},"ISSN":["1058-4838","1537-6591"],"issn-type":[{"value":"1058-4838","type":"print"},{"value":"1537-6591","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,9,15]]},"published":{"date-parts":[[2023,5,10]]}}}