{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:37:33Z","timestamp":1791859053638,"version":"4.3.4"},"reference-count":28,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T00:00:00Z","timestamp":1594425600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"GW Research Ltd"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    We investigated the effects of cannabidiol (CBD; 21\u2010day maintenance dose) on the pharmacokinetics (PK) of clobazam (CLB) and monitored the safety of CBD (or placebo) plus CLB in 20\u00a0patients with uncontrolled epilepsy on stable doses of CLB. Blood samples collected until 24 hours postdose were evaluated by liquid chromatography tandem mass spectrometry. PK parameters of CLB and major metabolite\n                    <jats:italic>N<\/jats:italic>\n                    \u2010desmethylclobazam (N\u2010CLB), valproic acid, stiripentol, levetiracetam, topiramate, plant\u2010derived highly purified CBD (Epidiolex in the United States; 100 mg\/mL oral solution) and its major metabolites were derived using noncompartmental analysis. There was no evidence of a drug\u2010drug interaction (DDI) between CBD and CLB: geometric mean ratio (GMR) of day\u00a033:day\u00a01 CLB was 1.0 (90%CI, 0.8\u20101.2) for C\n                    <jats:sub>max<\/jats:sub>\n                    and 1.1 (90%CI, 0.9\u20101.2) for AUC\n                    <jats:sub>tau<\/jats:sub>\n                    . There was a significant DDI between CBD and N\u2010CLB: the GMR of day\u00a033:day\u00a01 N\u2010CLB was 2.2 (90%CI, 1.4\u20103.5) for C\n                    <jats:sub>max<\/jats:sub>\n                    and 2.6 (90%CI, 2.0\u20103.6) for AUC\n                    <jats:sub>tau<\/jats:sub>\n                    . Placebo had no effect on CLB or N\u2010CLB; CBD had no effect on levetiracetam. Data were insufficient regarding DDIs with other antiepileptic drugs. The safety profile of CBD (20\u00a0mg\/kg\/day) with CLB was acceptable; all but 1 adverse events (AEs) were mild or moderate. One serious AE (seizure cluster) led to CBD discontinuation. One patient withdrew after intolerable AEs. Although there was no evidence of a CBD and CLB DDI, there was a significant DDI between CBD and N\u2010CLB. The safety profile of GW Pharmaceuticals\u2019 CBD formulation with CLB was consistent with other GW\u2010sponsored trials.\n                  <\/jats:p>","DOI":"10.1002\/jcph.1634","type":"journal-article","created":{"date-parts":[[2020,7,11]],"date-time":"2020-07-11T17:42:33Z","timestamp":1594489353000},"page":"1304-1313","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["A Phase 2, Double\u2010Blind, Placebo\u2010Controlled Trial to Investigate Potential Drug\u2010Drug Interactions Between Cannabidiol and Clobazam"],"prefix":"10.1002","volume":"60","author":[{"given":"Kevan E.","family":"VanLandingham","sequence":"first","affiliation":[{"name":"Greenwich Biosciences Inc.  Carlsbad California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Crockett","sequence":"additional","affiliation":[{"name":"GW Research Ltd.  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lesley","family":"Taylor","sequence":"additional","affiliation":[{"name":"GW Research Ltd.  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilmour","family":"Morrison","sequence":"additional","affiliation":[{"name":"GW Research Ltd.  Cambridge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,11]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1611618"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1714631"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000005254"},{"key":"e_1_2_13_5_1","unstructured":"Greenwich Biosciences. EPIDIOLEX\u00ae(cannabidiol) oral solution prescribing information. Carlsbad CA: Greenwich Biosciences; 2018."},{"key":"e_1_2_13_6_1","unstructured":"GW Research. EPIDYOLEX\u00ae(cannabidiol oral solution) summary of product characteristics. B.V. Amersfoort Nederlands: GW Research;2019."},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(18)30136-3"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2011-1197"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-015-0377-3"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1211204110"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12944"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2011.05.018"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389200217666151210142051"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.3109\/03602532.2013.849268"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.32.11.1279"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.1979.tb04664.x"},{"key":"e_1_2_13_17_1","unstructured":"Lundbeck. ONFI\u00ae (clobazam): prescribing information. Deerfield IL: Lundbeck; 2016."},{"key":"e_1_2_13_18_1","unstructured":"FriedmanD CilioMR TiltonN et\u00a0al. The effect of Epidiolex (cannabidiol) on serum levels of concomitant anti\u2010epileptic drugs in children and young adults with treatment\u2010resistant epilepsy in an expanded access program. Paper presented at: American Epilepsy Society; December 5\u20109 2014; Seattle WA. Abstract No. 2.309."},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13852"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13060"},{"key":"e_1_2_13_21_1","unstructured":"World Medical Association. World Medical Association Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects.https:\/\/www.wma.net\/what-we-do\/medical-ethics\/declaration-of-helsinki\/doh-oct2000\/. Published 2000. Accessed October 25 2019."},{"key":"e_1_2_13_22_1","unstructured":"International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use.ICH Harmonised Tripartite Guidelines: Guidelines for Good Clinical Practice E6(R1).European Medicines Agency (EMA) Amsterdam the Netherlands;1996.https:\/\/www.ich.org\/page\/efficacy-guidelines."},{"key":"e_1_2_13_23_1","volume-title":"Guideline on Clinical Investigation of Medicinal Products in the Treatment of Epileptic Disorders","author":"Committee for Medicinal Products for Human Use","year":"2010"},{"key":"e_1_2_13_24_1","volume-title":"Guidelines for the Clinical Evaluation of Antiepileptic Drugs (Adults and Children","author":"Center for Drug Evaluation and Research","year":"1981"},{"key":"e_1_2_13_25_1","volume-title":"Clinical Drug Interaction Studies \u2014 Study Design, Data Analysis, and Clinical Implications Guidance for Industry","author":"Center for Drug Evaluation and Research","year":"2017"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpdd.665"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-018-0578-5"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.200790152"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(15)00379-8"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcph.1634","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1634","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.1634","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.1634","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T02:49:36Z","timestamp":1693882176000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.1634"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,11]]},"references-count":28,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2020,10]]}},"alternative-id":["10.1002\/jcph.1634"],"URL":"https:\/\/doi.org\/10.1002\/jcph.1634","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,11]]},"assertion":[{"value":"2019-11-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}