{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T14:56:59Z","timestamp":1774364219381,"version":"3.50.1"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100013322","name":"European Federation of Pharmaceutical Industries and Associations","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","award":["NCT06354257"],"award-info":[{"award-number":["NCT06354257"]}],"id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","award":["EudraCT: 2023\u2010507839\u201038\u201000"],"award-info":[{"award-number":["EudraCT: 2023\u2010507839\u201038\u201000"]}],"id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    New drugs are urgently needed to treat drug\u2010resistant tuberculosis in combination regimens. Ganfeborole demonstrated bactericidal activity and good tolerability in clinical trials. In preclinical studies, ganfeborole showed embryofetal developmental effects, currently mandating highly effective non\u2010user dependent contraception in women of childbearing potential. We conducted a Phase 1, open\u2010label, single\u2010center, fixed sequence, 1\u2010way drug\u2013drug interaction (DDI) study in 20 healthy women of non\u2010childbearing potential aged 18\u201065 years. The primary objective was to assess ganfeborole's effect at steady\u2010state (20 mg daily) on single dose pharmacokinetics of ethinyl estradiol [EE] 0.03 mg\/levonorgestrel [LNG] 15 mg (Bayer). Endpoints were EE and LNG area under the plasma concentration\u2010time curve extrapolated to infinity (AUC\n                    <jats:sub>(0\u2010inf)<\/jats:sub>\n                    ) and maximum concentration (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    ). Unexpected fluctuations in individual EE and LNG plasma concentration\u2010time profiles limited the number of acceptable endpoints for the analysis. Geometric mean ratios (GMR; EE\/LNG+ganfeborole versus EE\/LNG alone) and respective 90% confidence intervals (CI) for EE\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    (0.96, 0.85\u20101.09), LNG AUC\n                    <jats:sub>(0\u2010inf)<\/jats:sub>\n                    (1.10, 0.98\u20101.23) and LNG\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>max<\/jats:sub>\n                    (1.08, 0.97\u20101.19) met criteria for lack of DDI (90% CI 0.80\u20101.25). However, the GMR for EE AUC\n                    <jats:sub>(0\u2010inf)<\/jats:sub>\n                    was 0.88, with 90% CI 0.55\u20101.41. While post\u2010hoc analyses on partial AUCs (up to 8 and 24 h) provided GMR 90% CIs within 0.80\u20101.25, a lack of DDI could not be concluded. No treatment\u2010related adverse events were reported. Further assessments of potential DDI between ganfeborole and combined oral contraceptives are warranted. Future trials will maintain strict contraception requirements.\n                  <\/jats:p>\n                  <jats:p>Clinical Trial Registration: NCT06354257 (registration date: 2024\u201004\u201003); EudraCT: 2023\u2010507839\u201038\u201000<\/jats:p>","DOI":"10.1002\/jcph.70161","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T21:27:19Z","timestamp":1773005239000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined Oral Contraceptive Drug\u2013Drug Interaction Study With Ganfeborole, a New Anti\u2010Tuberculosis Agent"],"prefix":"10.1002","volume":"66","author":[{"given":"Laura","family":"Iavarone","sequence":"first","affiliation":[{"name":"Parexel International  Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia M.","family":"Lavezzi","sequence":"additional","affiliation":[{"name":"Parexel International  Dublin Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio J.","family":"Carcas","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department La Paz University Hospital IdiPAZ, and School of Medicine Universidad Aut\u00f3noma de Madrid  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tetyana","family":"Chaychenko","sequence":"additional","affiliation":[{"name":"GSK  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"Gabarro\u2010Carrion","sequence":"additional","affiliation":[{"name":"GSK  Tres Cantos Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arturo G\u00f3mez L\u00f3pez de las","family":"Huertas","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department La Paz University Hospital IdiPAZ, and School of Medicine Universidad Aut\u00f3noma de Madrid  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Gresham","sequence":"additional","affiliation":[{"name":"GSK  Stevenage UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alicia","family":"Mar\u00edn\u2010Cand\u00f3n","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department La Paz University Hospital IdiPAZ, and School of Medicine Universidad Aut\u00f3noma de Madrid  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-0991-9643","authenticated-orcid":false,"given":"Sophie L.","family":"Penman","sequence":"additional","affiliation":[{"name":"GSK  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katie","family":"Rolfe","sequence":"additional","affiliation":[{"name":"GSK  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simon","family":"Tiberi","sequence":"additional","affiliation":[{"name":"GSK  London UK"},{"name":"Blizard Institute Barts and The London School of Medicine and Dentistry Queen Mary University of London  London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Barros\u2010Aguirre","sequence":"additional","affiliation":[{"name":"GSK  Tres Cantos Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto M.","family":"Borobia","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Department La Paz University Hospital IdiPAZ, and School of Medicine Universidad Aut\u00f3noma de Madrid  Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"the ERA4TB consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,6]]},"reference":[{"key":"e_1_2_11_2_1","unstructured":"Global tuberculosis report 2024. World Health Organization.2024. Accessed 24 April 24 2025.https:\/\/www.who.int\/teams\/global\u2010tuberculosis\u2010programme\/tb\u2010reports\/global\u2010tuberculosis\u2010report\u20102024"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2023-081209"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgph.0003578"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.2c00227"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"e_1_2_11_7_1","unstructured":"WHO operational handbook on tuberculosis. Module 4: Treatment \u2010 drug\u2010resistant tuberculosis treatment 2022 update.World Health Organization.2022. Accessed April 24 2025.https:\/\/www.who.int\/publications\/i\/item\/9789240065116"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(25)00218-X"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01339-16"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b00631"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00240-19"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.5588\/ijtld.21.0515"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02829-7"},{"key":"e_1_2_11_14_1","unstructured":"Platform assessing regimens and durations in a global multisite consortium for TB (PARADIGM4TB). National Library of Medicine. Accessed 24 April 24 2025.https:\/\/clinicaltrials.gov\/study\/NCT06114628"},{"key":"e_1_2_11_15_1","unstructured":"Early bactericidal activity safety & tolerability of oral GSK3036656 in a dual combination with novel and established antitubercular agents or standard of care in adults with rifampicin susceptible pulmonary tuberculosis. National Library of Medicine. Accessed May 1 2025.https:\/\/clinicaltrials.gov\/study\/NCT05382312?term&NCT05382312&rank=1"},{"key":"e_1_2_11_16_1","unstructured":"Guideline on the investigation of drug interactions. European Medicines Agency. Accessed 25 April 2025.https:\/\/www.ema.europa.eu\/en\/investigation\u2010drug\u2010interactions\u2010scientific\u2010guideline"},{"key":"e_1_2_11_17_1","unstructured":"Clinical drug interaction studies with combined oral contraceptives. United States Food and Drug Administration. Accessed February 21 2025.https:\/\/www.fda.gov\/regulatory\u2010information\/search\u2010fda\u2010guidance\u2010documents\/clinical\u2010drug\u2010interaction\u2010studies\u2010combined\u2010oral\u2010contraceptives\u2010guidance\u2010industry"},{"key":"e_1_2_11_18_1","unstructured":"European regimen accelerator for tuberculosis. ERA4TB. Accessed 13 June 2025.https:\/\/era4tb.org\/"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/d41573-024-00138-9"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13318-021-00728-7"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1610"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jia2.25858"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70161","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.70161","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70161","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T14:03:09Z","timestamp":1774360989000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":21,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/jcph.70161"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70161","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"2025-08-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70161"}}